title: Effect of ramipril vs amlodipine on renal outcomes in hypertensive nephrosclerosis: a randomized controlled trial. A calcium antagonist vs a non-calcium antagonist hypertension treatment strategy for patients with coronary artery disease. The International Verapamil-Trandolapril Study (INVEST): a randomized controlled trial. Treatment of mild-to-moderate hypertension with calcium channel blockers: a multicentre comparison of once-daily nifedipine GITS with once-daily amlodipine Progress report on the Nordic diltiazem study (NORDIL): an outcome study in hypertensive patients. Effects of Once-Daily Angiotensin-Converting Enzyme Inhibition and Calcium Channel Blockade-Based Antihypertensive Treatment Regimens on Left Ventricular Hypertrophy and Diastolic Filling in Hypertension: The Prospective Randomized Enalapril Study Evaluating Regression of Ventricular Enlargement (PR Multicenter isradipine diuretic atherosclerosis study (MIDAS). Design features. The Midas Research Group. Effect of blood pressure control and antihypertensive drug regimen on quality of life: the African American Study of Kidney Disease and Hypertension (AASK) Pilot Study. Design and baseline characteristics of participants in the African American Study of Kidney Disease and Hypertension (AASK) Pilot Study. Calcium antagonists and mortality risk in men and women with hypertension in the Framingham Heart Study. Rationale and design of the International Verapamil SR/Trandolapril Study (INVEST): an Internet-based randomized trial in coronary artery disease patients with hypertension. Fosinopril Versus Amlodipine Comparative Treatments Study: A Randomized Trial to Assess Effects on Plasminogen Activator Inhibitor-1 Effect of calcium channel or beta-blockade on the progression of diabetic nephropathy in African Americans. Calcium channel blockade and cardiovascular prognosis in the European trial on isolated systolic hypertension. Randomised trial of effects of calcium antagonists compared with diuretics and β-blockers on cardiovascular morbidity and mortality in hypertension: the Nordic Diltiazem (NORDIL) study Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes. Captopril, nifedipine and their combination for therapy of hypertensive urgencies. Syst-Eur. A multicentre trial on the treatment of isolated systolic hypertension in the elderly: Objectives, protocol, and organization Outcome Results of the Fosinopril Versus Amlodipine Cardiovascular Events Randomized Trial (FACET) in Patients With Hypertension and NIDDM Calcium Antagonist Lacidipine Slows Down Progression of Asymptomatic Carotid Atherosclerosis: Principal Results of the European Lacidipine Study on Atherosclerosis (ELSA), a Randomized, Double-Blind, Long-Term Trial Randomised trial of old and new antihypertensive drugs in elderly patients: cardiovascular mortality and morbidity the Swedish Trial in Old Patients with Hypertension-2 study Effect of blood pressure lowering and antihypertensive drug class on progression of hypertensive kidney disease: results from the AASK trial. Outcomes in hypertensive patients at high cardiovascular risk treated with regimens based on valsartan or amlodipine: the VALUE randomised trial Effect of single-drug therapy on reduction of left ventricular mass in mild to moderate hypertension: comparison of six antihypertensive agents. The Department of Veterans Affairs Cooperative Study Group on Antihypertensive Agents. Early prediction of severity in acute pancreatitis by urinary trypsinogen activation peptide: a multicentre study STOP-Hypertension 2: a prospective intervention trial of "newer" versus "older" treatment alternatives in old patients with hypertension. Swedish Trial in Old Patients with Hypertension. Hydrochlorothiazide is superior to isradipine for reduction of left ventricular mass: results of a multicenter trial. The Isradipine Study Group. Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. The Valsartan Antihypertensive Long-term Use Evaluation (VALUE) trial of cardiovascular events in hypertension. Rationale and design. Treatment of Isolated Systolic Hypertension: The SHELL Study Results The effect of nisoldipine as compared with enalapril on cardiovascular outcomes in patients with non-insulin-dependent diabetes and hypertension. Calcium channel blockers and cardiac mortality in the treatment of hypertension: a report from the Department of Health Hypertension Care Computing Project (DHCCP) Cardiovascular Outcomes in the Irbesartan Diabetic Nephropathy Trial of Patients with Type 2 Diabetes and Overt Nephropathy Background and design of the new U.S. trial on diet and drug treatment of "mild" hypertension (TOMHS). Antihypertensive monotherapy with nisoldipine CC is superior to enalapril in black patients with severe hypertension. A comparison of the acute hypotensive effects of two different doses of nifedipine. MIDAS: Hypertension and Atherosclerosis A Trial of the Effects of Antihypertensive Drug Treatment on Atherosclerosis Effects of intensive blood-pressure lowering and low-dose aspirin in patients with hypertension: principal results of the Hypertension Optimal Treatment (HOT) randomised trial The ABCD (Appropriate Blood Pressure Control in Diabetes) trial. Rationale and design of a trial of hypertension control (moderate or intensive) in type II diabetes. Morbidity and mortality in patients randomised to double-blind treatment with a long-acting calcium-channel blocker or diuretic in the International Nifedipine GITS study: Intervention as a Goal in Hypertension Treatment (INSIGHT) Prospective randomized open blinded end-point (PROBE) study. A novel design for intervention trials. Prospective Randomized Open Blinded End-Point. Prevention of cardiovascular events with an antihypertensive regimen of amlodipine adding perindopril as required versus atenolol adding bendroflumethiazide as required, in the Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm (ASCOT-BPLA): a multicentre randomised controlled tri The Irbesartan type II diabetic nephropathy trial: study design and baseline patient characteristics. For the Collaborative Study Group. Rationale and design for the Controlled ONset Verapamil INvestigation of Cardiovascular Endpoints (CONVINCE) Trial. Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs diuretic: The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). Calcium channel blockers versus other antihypertensive therapies on progression of NIDDM associated nephropathy. The risk of myocardial infarction associated with antihypertensive drug therapies. Rationale, design, methods and baseline demography of participants of the Anglo-Scandinavian Cardiac Outcomes Trial Treatment of elderly hypertensives in Japan: National Intervention Cooperative Study in Elderly Hypertensives. The National Intervention Cooperative Study Group. Baseline Characteristics and Early Blood Pressure Control in the CONVINCE Trial The Verapamil in Hypertension and Atherosclerosis Study (VHAS): Results of long‐term randomized treatment with either verapamil or chlorthalidone on carotid intima‐media thickness The Swedish Trial in old patients with hypertension-2 (STOP-hypertension-2): a progress report. Cardiovascular outcomes in the African American Study of Kidney Disease and Hypertension (AASK) Trial. Major outcomes in moderately hypercholesterolemic, hypertensive patients randomized to pravastatin vs usual care: The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT-LLT). Long-term survival and use of antihypertensive medications in older persons. Final outcome results of the Multicenter Isradipine Diuretic Atherosclerosis Study (MIDAS). A randomized controlled trial. Comparison of active treatment and placebo in older Chinese patients with isolated systolic hypertension Characteristics of participants at baseline in the Treatment of Mild Hypertension Study (TOMHS).
abstract: CONTEXT Incidence of end-stage renal disease due to hypertension has increased in recent decades , but the optimal strategy for treatment of hypertension to prevent renal failure is unknown , especially among African Americans . OBJECTIVE To compare the effects of an angiotensin-converting enzyme ( ACE ) inhibitor ( ramipril ) , a dihydropyridine calcium channel blocker ( amlodipine ) , and a beta-blocker ( metoprolol ) on hypertensive renal disease progression . DESIGN , SETTING , AND PARTICIPANTS Interim analysis of a r and omized , double-blind , 3 x 2 factorial trial conducted in 1094 African Americans aged 18 to 70 years with hypertensive renal disease ( glomerular filtration rate [ GFR ] of 20 - 65 mL/min per 1.73 m(2 ) ) enrolled between February 1995 and September 1998 . This report compares the ramipril and amlodipine groups following discontinuation of the amlodipine intervention in September 2000 . INTERVENTIONS Participants were r and omly assigned to receive amlodipine , 5 to 10 mg/d ( n = 217 ) , ramipril , 2.5 to 10 mg/d ( n = 436 ) , or metoprolol , 50 to 200 mg/d ( n = 441 ) , with other agents added to achieve 1 of 2 blood pressure goals . MAIN OUTCOME MEASURES The primary outcome measure was the rate of change in GFR ; the main secondary outcome was a composite index of the clinical end points of reduction in GFR of more than 50 % or 25 mL/min per 1.73 m(2 ) , end-stage renal disease , or death . RESULTS Among participants with a urinary protein to creatinine ratio of > 0.22 ( corresponding approximately to proteinuria of more than 300 mg/d ) , the ramipril group had a 36 % ( 2.02 [ SE , 0.74 ] mL/min per 1.73 m(2)/y ) slower mean decline in GFR over 3 years ( P = .006 ) and a 48 % reduced risk of the clinical end points vs the amlodipine group ( 95 % confidence interval [ CI ] , 20%-66 % ) . In the entire cohort , there was no significant difference in mean GFR decline from baseline to 3 years between treatment groups ( P = .38 ) . However , compared with the amlodipine group , after adjustment for baseline covariates the ramipril group had a 38 % reduced risk of clinical end points ( 95 % CI , 13%-56 % ) , a 36 % slower mean decline in GFR after 3 months ( P = .002 ) , and less proteinuria ( P<.001 ) . CONCLUSION Ramipril , compared with amlodipine , retards renal disease progression in patients with hypertensive renal disease and proteinuria and may offer benefit to patients without proteinuria CONTEXT Despite evidence of efficacy of antihypertensive agents in treating hypertensive patients , safety and efficacy of antihypertensive agents for coronary artery disease ( CAD ) have been discerned only from subgroup analyses in large trials . OBJECTIVE To compare mortality and morbidity outcomes in patients with hypertension and CAD treated with a calcium antagonist strategy ( CAS ) or a non-calcium antagonist strategy ( NCAS ) .  DESIGN , SETTING , AND PARTICIPANTS R and omized , open label , blinded end point study of 22 576 hypertensive CAD patients aged 50 years or older , which was conducted September 1997 to February 2003 at 862 sites in 14 countries . INTERVENTIONS Patients were r and omly assigned to either CAS ( verapamil sustained release ) or NCAS ( atenolol ) . Strategies specified dose and additional drug regimens . Tr and olapril and /or hydrochlorothiazide was administered to achieve blood pressure goals according to guidelines from the sixth report of the Joint National Committee on Prevention , Detection , Evaluation , and Treatment of High Blood Pressure ( JNC VI ) of less than 140 mm Hg ( systolic ) and less than 90 mm Hg ( diastolic ) ; and less than 130 mm Hg ( systolic ) and less than 85 mm Hg ( diastolic ) if diabetes or renal impairment was present . Tr and olapril was also recommended for patients with heart failure , diabetes , or renal impairment . MAIN OUTCOME MEASURES Primary : first occurrence of death ( all cause ) , nonfatal myocardial infa rct ion , or nonfatal stroke ; other : cardiovascular death , angina , adverse experiences , hospitalizations , and blood pressure control at 24 months . RESULTS At 24 months , in the CAS group , 6391 patients ( 81.5 % ) were taking verapamil sustained release ; 4934 ( 62.9 % ) were taking tr and olapril ; and 3430 ( 43.7 % ) were taking hydrochlorothiazide . In the NCAS group , 6083 patients ( 77.5 % ) were taking atenolol ; 4733 ( 60.3 % ) were taking hydrochlorothiazide ; and 4113 ( 52.4 % ) were taking tr and olapril . After a follow-up of 61 835 patient-years ( mean , 2.7 years per patient ) , 2269 patients had a primary outcome event with no statistically significant difference between treatment strategies ( 9.93 % in CAS and 10.17 % in NCAS ; relative risk [ RR ] , 0.98 ; 95 % confidence interval [ CI ] , 0.90 - 1.06 ) . Two-year blood pressure control was similar between groups . The JNC VI blood pressure goals were achieved by 65.0 % ( systolic ) and 88.5 % ( diastolic ) of CAS and 64.0 % ( systolic ) and 88.1 % ( diastolic ) of NCAS patients . A total of 71.7 % of CAS and 70.7 % of NCAS patients achieved a systolic blood pressure of less than 140 mm Hg and diastolic blood pressure of less than 90 mm Hg . CONCLUSION The verapamil-tr and olapril-based strategy was as clinical ly effective as the atenolol-hydrochlorothiazide-based strategy in hypertensive CAD patients SUMMARY Background : Hypertension is one of the most important causes of cardiovascular disease , and treatment of hypertension leads to a significant reduction in cardiovascular mortality and morbidity . Although calcium channel blockers are regarded as an important part of the therapeutic armamentarium against cardiovascular diseases , and are among the most frequently prescribed antihypertensive medications , concern has been aroused about these drugs , particularly the short-acting dihydropyridine derivatives . However , the value of nifedipine GITS ( Adalat-Crono * ) , the long-acting dihydropyridine , is in need of being re-established . * Adalat-Crono is a registered tradename of Bayer AG , Leverkusen , Germany Objective : To compare the effectiveness , safety and tolerability of once-daily nifedipine and amlodipine treatment in patients with mild-to-moderate essential hypertension . Design : R and omised multicentre trial with an open comparison of treatments for 12 weeks , with a preceding placebo run-in period of 2 weeks ( patients on beta-blockers at the time of enrolment entered a m and atory 2-week wash-out period before being allowed in the placebo run-in period ; this wash-out period was one week for patients using any antihypertensive medication other than beta-blockers ) . Setting : Nine centres ( all university hospitals ) in Turkey . Patients : 155 patients with essential hypertension ( diastolicblood pressure 95 - 109 mmHg ) . Interventions : Initial treatment ( step 1 ) consisted of 30 mg nifedipine GITS ( n = 76 ; ( Adalat-Crono tablets ) , or 5 mg amlodipine ( n = 79 ; Norvasc * 5-mg tablets ) , either administered once daily , as a morning dose , or if the blood pressure was not below 140/90 mmHg , or the reduction in diastolic blood pressure was lower than 10 mmHg after a treatment period of 6 weeks , the dose was increased ( Step 2 ) to 60 mg once daily in the nifedipine group , or 10 mg once daily in the amlodipine group . Main efficacy parameter : Diastolic blood pressure at trough after 12 weeks of active compound therapy adjusted to baseline . Results : After 12 weeks of treatment , the mean diastolic blood pressure was 83.1 and 81.9 mmHg , in the nifedipine and amlodipine groups , respectively ( p = 0.436 ) . The mean decrease in systolic blood pressure ( 28.5 ± 11.9 and 28.2 ± 11.2 mmHg in the nifedipine and amlodipine groups , respectively ) and the mean decrease in diastolic blood pressure ( 16.4 ± 7.0 and 17.5 ± 6.9 mmHg in the nifedipine and amlodipine groups , respectively ) , as well as the responder rates ( 88.1 % and 92.1 % , in the nifedipine and amlodipine groups , respectively ) were comparable at the end of the study . No significant differences between groups were detected in the efficacy parameters assessed in this study . Both drugs were well tolerated . The overall incidence of adverse events was 7.9 % in the nifedipine group and 10.1 % in the amlodipine group . However , more patients discontinued treatment prematurely in the amlodipine group ( 13 patients ; 19.7 % ) , than in the nifedipine group ( four patients ; 5.6 % ) . Conclusions : The results of this study demonstrated that once-daily nifedipine in GITS formulation and amlodipine are comparably safe and effective treatment options in patients with mild-to-moderate essential hypertensi on NORDIL -- the Nordic Diltiazem Study (NORDIL)--is a prospect i ve , r and omized , open blinded-endpoint ( PROBE ) , multicenter , parallel-group morbidity/mortality outcome study in hypertensive patients design ed to compare an intervention strategy based on the calcium antagonist diltiazem with a strategy based on conventional antihypertensive drug treatment ( diuretics or beta-adrenergic blockers ) .  Patient recruitment was started in Norway and Sweden in September 1992 , and ended on December 15 , 1996 , when 10.896 male and female patients , aged 50 - 74 years , with essential hypertension had been r and omized . In this paper we describe the baseline data of the patient cohort and blood pressures achieved in the two treatment groups during the early part of the study . The patient cohort consists of 5294 males and 5602 females with a mean age of 59.6 and 60.3 years , respectively . Concomitant disorders and risk factors in the cohort are : smoking 22 % , ischemic heart disease 3.0 % , previous myocardial infa rct ion ( MI ) 2.0 % , previous stroke 1.5 % , diabetes mellitus 7.0 % , and renal impairment 0.3 % . There were no differences between the treatment groups in these respects . The blood pressure treatment goal is a target diastolic blood pressure of < or = 90 mmHg or a 10 % diastolic blood pressure reduction from the inclusion pressure . In the treatment group r and omized to a diltiazem-based treatment strategy , blood pressure was 174/106 mmHg at baseline and 156/90 mmHg after 12 months of follow-up on active treatment . In the group r and omized to a conventional treatment strategy , baseline blood pressure at r and omization was 173/106 mmHg and 153/90 mmHg after 12 months on active therapy . The NORDIL study will terminate on October 31 , 1999 and the final results should be available by mid-2000 Background —The Prospect i ve R and omized Enalapril Study Evaluating Regression of Ventricular Enlargement ( PRESERVE ) study was design ed to test whether enalapril achieves greater left ventricular ( LV ) mass reduction than does a nifedipine gastrointestinal treatment system by a prognostically meaningful degree on a population basis ( 10 g/m2 ) . Methods and Results —An ethnically diverse population of 303 men and women with essential hypertension and increased LV mass at screening echocardiography were enrolled at clinical centers on 4 continents and studied by echocardiography at baseline and after 6- and 12-month r and omized therapy . Clinical examination and blinded echocardiogram readings 48 weeks after study entry in an intention-to-treat analysis of 113 enalapril-treated and 122 nifedipine-treated patients revealed similar reductions in systolic/diastolic pressure ( −22/12 versus −21/13 mm Hg ) and LV mass index ( −15 versus −17g/m2 , both P > 0.20 ) . No significant between-treatment difference was detected in population subsets defined by monotherapy treatment , sex , age , race , or severity of baseline hypertrophy . Similarly , there was no between-treatment difference in change in velocities of early diastolic or atrial phase transmitral blood flow . More enalapril-treated than nifedipine-treated patients required supplemental treatment with hydrochlorothiazide ( 59 % versus 34 % , P < 0.001 ) but not atenolol ( 27 % versus 22 % , NS ) . Conclusions —Once-daily antihypertensive treatment with enalapril or long-acting nifedipine , plus adjunctive hydrochlorothiazide and atenolol when needed to control blood pressure , both had moderately beneficial and statistically indistinguishable effects on regression of LV hypertrophy The Multicenter Isradipine Diuretic Atherosclerosis Study is a r and omized , double-blind , clinical trial design ed to compare the effectiveness of isradipine against hydrochlorothiazide in retarding the rate of progression of atherosclerotic lesions in the carotid arteries of hypertensive subjects . Eight hundred hypertensive men and women , 40 years of age or older , with minor plaques , are being recruited at eight clinical centers in the United States and will be followed for three years . Quantification of the atherosclerotic lesions at baseline and semiannually is done using B-mode ultrasonography . The background of the trial and its design features are discussed The African American Study of Kidney Disease and Hypertension ( AASK ) Pilot Study evaluated the feasibility of carrying out a r and omized , multicenter , 7-year clinical trial to determine the effects of two goal levels of blood pressure control and three antihypertensive drug regimens on decline in glomerular filtration rate in African Americans with clinical ly diagnosed hypertensive nephrosclerosis . Participants were r and omized to either a usual mean arterial blood pressure ( MAP ) goal group ( 102 - 107 mm Hg ) or a low-MAP goal group ( < or = 92 mm Hg ) and to a drug regimen ( initial therapy with either atenolol , amlodipine , or enalapril ) . Quality of life was assessed by the Medical Outcomes Short-Form 36 ( MOS SF-36 ) at baseline and the last follow-up visit for 84 of the 94 participants of the AASK Pilot Study . Symptoms were assessed at baseline and throughout the course of therapy by participant self-report . Mean SF-36 scores increased significantly on physical functioning ( 9.2 ) , role limitations ( physical ) ( 19.0 ) , social functioning ( 9.0 ) , and vitality dimensions ( 5.6 ) from baseline to the last follow-up visit in the usual MAP goal group . Scores for the eight health dimensions assessed by the MOS SF-36 did not change significantly during the same time period either in the low-MAP goal group or in any of the drug regimens . The mean score for general health perception was significantly lower at the last follow-up visit in the enalapril drug regimen ( 49.9 ) compared to drug regimens with atenolol ( 65.4 ) or amlodipine ( 63.9 ) . Physical functioning , role limitations ( emotional ) , social functioning , mental health , vitality , and general health perception scores were negatively correlated with self-reported symptoms during treatment . We conclude that selected dimensions of quality of life improved during the AASK Pilot Study only in participants r and omized to the usual MAP goal group . Significant differences between MAP goal groups and drug regimens at the end of follow-up were observed for only a few health dimensions Hypertension and end-stage renal disease ( ESRD ) are major causes of morbidity and mortality in the United States , especially among African Americans . The African American Study of Kidney Disease and Hypertension ( AASK ) Pilot Study evaluated the feasibility of conducting a long-term clinical trial to compare the effects of two levels of blood pressure control and three different antihypertensive drug regimens on the rate of decline in glomerular filtration rate ( GFR ) in African Americans with clinical ly diagnosed hypertensive renal disease . African American men and women aged 18 - 70 years with a GFR of 25 - 70 ml/min/ 1.73m2 and hypertension were r and omized in a 3 x 2 factorial design to initial treatment with either an angiotensin-converting enzyme inhibitor ( enalapril ) , a calcium channel blocker ( amlodipine ) , or a beta blocker ( atenolol ) and to a mean arterial blood pressure ( goal MAP ) of either 102 - 107 mm Hg or < or = 92 mm Hg . Furosemide , doxazosin , clonidine , hydralazine , and minoxidil were added sequentially until goal MAP was achieved . To compare the pathologic diagnosis with the clinical diagnosis of renal disease , study participants without contraindication were also asked to undergo a renal biopsy . The goals of the AASK Pilot Study were to evaluate recruitment techniques , adherence to prescribed antihypertensive drug regimens , ability of the antihypertensive regimens to achieve blood pressure goals , rates of participation in scheduled clinic visits and procedures , and variability of GFR measurements . A further goal was to obtain renal biopsy data in at least 75 % of the r and omized study participants . Compared to the ESRD patient population whose renal disease is caused by hypertension , women were underrepresented in the AASK Pilot Study . AASK Pilot Study participants had higher  unemployment rates and lower income levels than African Americans in the general U.S. population BACKGROUND Several recent studies have suggested that calcium antagonist drugs , which are widely used for the treatment of hypertension , are associated with increased risk of cardiovascular disease . These studies have cast doubts on the long-term safety of calcium antagonists . OBJECTIVE To examine the association of calcium antagonist use with mortality in subjects with hypertension followed up in the Framingham Heart Study . SUBJECTS AND METHODS We stratified 3539 subjects ( mean+/-SD age , 64+/-13 years ) from the Framingham Heart Study who had hypertension at routine clinic examinations , according to the use of calcium antagonists and presence of coronary heart disease at the baseline examination . At each follow-up examination ( every 2 - 4 years ) , subjects were reclassified with regard to the use of calcium antagonists . The end point of the study was all-cause mortality . Hazard ratios and 95 % confidence intervals associated with the use of calcium antagonists were obtained using Cox proportional hazards regression models . RESULTS There were 970 deaths during follow-up . Hazard ratios for mortality associated with the use of calcium antagonists were 0.93 ( 95 % confidence interval , 0.72 - 1.21 ; P=.59 ) for subjects with hypertension without coronary heart disease , and 0.92 ( 95 % confidence interval , 0.69 - 1.24 ; P=.58 ) for those with coronary heart disease at baseline . All models were adjusted for age , sex , current smoking , systolic and diastolic blood pressure , use of beta-blockers , and use of other antihypertensive medications . CONCLUSIONS In this cohort of 3539 subjects with hypertension there were no differences in mortality among subjects with hypertension using a calcium antagonist compared with those who were not . Results were similar among subjects with hypertension with and without coronary heart disease . The results of ongoing long-term , r and omized clinical trials will provide more definitive data on the safety of calcium antagonists OBJECTIVES The primary objective of the International Verapamil SR/Tr and olapril Study ( INVEST ) is to compare the risk for adverse outcomes ( all-cause mortality , nonfatal myocardial infa rct ion [ MI ] or nonfatal stroke ) in hypertensive patients with coronary artery disease ( CAD ) treated with either a calcium antagonist-based or a noncalcium antagonist-based strategy .  BACKGROUND Treatment recommendations for hypertension include initial therapy with a diuretic or beta-adrenergic blocking agent , for which reductions in morbidity and mortality are documented from r and omized trials but are less than expected from epidemiologic data . For this reason , recent attention has focused on calcium antagonists or angiotensin-converting enzyme inhibitors . While these agents reduce blood pressure , outcome data from large r and omized trials are lacking , but some case-control data , dominated by short-acting dihydropyridines , suggest an increased risk of cardiovascular events . These studies had method ologic limitations and did not differentiate among calcium antagonist types and formulations . Several studies differentiating among calcium antagonist types and an overview of published r and omized trials show no increased risk with verapamil and suggestion for benefit in CAD patients . METHODS A total of 27,000 CAD patients with hypertension will be r and omized at 1,500 primary care sites to receive either a calcium antagonist-based ( verapamil ) or beta-blocker/diuretic-based ( atenolol/hydrochlorothiazide ) antihypertensive care strategy . The study uses a novel , electronic " paper-less " system for direct on-screen data entry , r and omization and drug distribution from a mail pharmacy linked to the coordination center via the Internet . RESULTS Contract negotiations with the United States and international sites are ongoing . Patients being enrolled are predominantly elderly ( 72 % aged 60 years or older ) men ( 54 % ) , with either an abnormal coronary angiogram or prior MI ( 71 % ) . In addition to hypertension , CAD and elderly age , most patients ( 89 % ) have one or more associated conditions ( diabetes , dyslipidemia , smoking , cerebral or peripheral vascular disease , etc . ) contributing to increased risk for adverse outcome . While 26 % have diabetes , most of these are noninsulin dependent . Using the protocol strategies , target blood pressures ( according to JNC VI ) have been reached in 58 % at the fourth visit , and as expected most ( 89 % ) are requiring multiple antihypertensive drugs . CONCLUSION The design and baseline characteristics of the initial patients recruited for a prospect i ve , r and omized , international , multicenter study comparing two therapeutic strategies to control hypertension in CAD patients are described Background —ACE inhibitors and calcium antagonists may modulate fibrinolysis . We conducted a r and omized controlled trial to assess the effects of these drugs on plasminogen activator inhibitor-1 ( PAI-1 ) antigen , an inhibitor of fibrinolysis . Methods and Results — Participants with hypertension and type 2 diabetes mellitus ( n=96 , 51 % black ) were r and omized after an initial 4 weeks of placebo to double-blind 20 or 40 mg fosinopril or 5 or 10 mg amlodipine daily for 4 weeks in a fixed-dose regimen . After 4 weeks of placebo washout , the patients received 4 weeks of crossover treatments . After treatment with placebo  , systolic and diastolic blood pressure were 143±2 and 86±1 mm Hg and plasma PAI-1 was 43.4±2.3 ng/mL. Amlodipine achieved a greater systolic and diastolic blood pressure reduction than fosinopril ( 10 mm Hg versus 8 mm Hg , P = 0.029 , and 5 mm Hg versus 3 mm Hg , P = 0.040 , respectively ) but tended to increase PAI-1 , whereas fosinopril tended to decrease PAI-1 ( 5.4±3.6 versus −3.8±2.5 ng/mL , P = 0.045 ) . The PAI-1 changes depended on drug dose ( 6.5±6.1 and 3.4±3.9 ng/mL with amlodipine 10 and 5 mg , respectively , and −0.4±3.1 and −7.4±4.0 ng/mL with fosinopril 20 and 40 mg , respectively , P for trend 0.024 ) . No significant differences between fosinopril and amlodipine were found for short-term changes in tissue plasminogen activator antigen , fibrinogen , C-reactive protein , and interleukin-6 . The findings were similar in black and white participants . Conclusions —Short-term treatment with fosinopril  significantly reduced PAI-1 compared with amlodipine  in a dose-dependent fashion . This effect , which was independent of blood pressure reduction , may account for the improved clinical outcomes achieved with ACE inhibitors compared with calcium antagonists beta-Blockers are known to slow the progression of diabetic nephropathy by lowering arterial pressure . Moreover , in individuals with diabetic nephropathy , antihypertensive agents that provide sustained reductions in proteinuria slow the rate of decline in renal function compared with agents without this antiproteinuric effect . To examine whether differential effects on proteinuria affect the progression of diabetic nephropathy , we conducted a r and omized study that compared the effects of a heart rate-lowering calcium channel blocker , sustained-release verapamil , with those of a beta-blocker , atenolol , on the progression of diabetic renal disease . The primary end point of the study was a change in creatinine clearance slope .  Thirty-four African Americans with the following inclusion criteria were r and omized to one of the two groups : serum creatinine greater than 1.4 mg/dL , proteinuria greater than 1500 mg/d , longer than a 5-year history of both non-insulin-dependent diabetes mellitus and hypertension , and exclusion of other renal diseases . Goal blood pressure was less than 140/90 mm Hg . All subjects received loop diuretics as second line agents to help achieve the blood pressure goal . Twenty-four-hour urinary protein and sodium excretions as well as creatinine clearance were measured at 6-month intervals . Blood pressure was measured every 3 months . After a mean follow-up of 54+/-6 months , the calcium channel blocker group demonstrated both a slower rate of decline in creatinine clearance ( -1.7+/-0.9 versus -3.7+/-1.4 mL/min per year per 1.73 m2 , P<.01 ) and a greater reduction in proteinuria compared with the atenolol group . Additionally , a greater proportion of the atenolol group had a 50 % or more increase in serum creatinine compared with the verapamil group ( 32+/-9 % versus 16+/-7 % , P<.05 ) . These between-group differences could not be explained by differences in blood pressure control . These data support the concept that antihypertensive agents that persistently maintain reductions in both arterial pressure and proteinuria slow the progression of diabetic renal disease in African Americans to a greater extent than those agents without these effects In the double-blind Systolic Hypertension in Europe ( Syst-Eur ) Trial , active treatment was initiated with nitrendipine ( 10 to 40 mg/d ) with the possible addition of enalapril ( 5 to 20 mg/d ) and /or hydrochlorothiazide ( 12.5 to 25 mg/d ) titrated or combined to reduce sitting systolic blood pressure by at least 20 mm Hg to < 150 mm Hg . In the control group , matching placebos were used similarly . In view of persistent concerns about the use of calcium channel blockers as first-line antihypertensive drugs , this report explored to what extent nitrendipine , administered alone , prevented cardiovascular complications .  Age at r and omization averaged 70.2 years and systolic/diastolic blood pressure 173.8/85.5 mm Hg . Of 2398 actively treated patients , 1327 took only nitrendipine ( average dose , 23.4 mg/d ) , and 1042 progressed to other treatments including nitrendipine ( n=757 ; 35.7 mg/d ) , enalapril ( n=783 ; 13.4 mg/d ) , and /or hydrochlorothiazide ( n=294 ; 21.0 mg/d ) . Compared with the whole placebo group ( n=2297 ) , patients receiving monotherapy with nitrendipine had 25 % ( P=0.05 ) fewer cardiovascular end points , and those progressing to other active treatments showed decreases ( P</=0 . 01 ) in total mortality ( 40 % ) , stroke ( 59 % ) , and all cardiovascular end points ( 39 % ) . Among the control patients , 863 used only the first-line placebo . Compared with this subgroup , patients receiving monotherapy with nitrendipine showed a nearly 50 % ( P</=0.004 ) reduction of all types of end points , including total and cardiovascular mortality . The full relative benefit from nitrendipine was seen as early as 6 months after r and omization . To ascertain that the benefit conferred by the dihydropyridine was not due to selection bias , the 1327 patients remaining on monotherapy with nitrendipine  were matched by gender , age , previous cardiovascular complications , and systolic blood pressure at entry with an equal number of placebo patients . In this analysis , nitrendipine reduced ( P</=0.05 ) cardiovascular mortality by 41 % , all cardiovascular end points by 33 % , and fatal and nonfatal cardiac end points by 33 % . Despite the limitations inherent in post hoc analyses , the present findings suggest that the calcium channel blocker nitrendipine , given as a single antihypertensive medication , prevents cardiovascular complications in older patients with isolated systolic hypertension BACKGROUND Calcium antagonists are a first-line treatment for hypertension . The effectiveness of diltiazem , a non-dihydropyridine calcium antagonist , in reducing cardiovascular morbidity or mortality is unclear . We compared the effects of diltiazem with that of diuretics , beta-blockers , or both on cardiovascular morbidity and mortality  in hypertensive patients . METHODS In a prospect i ve , r and omised , open , blinded endpoint study , we enrolled 10,881 patients , aged 50 - 74 years , at health centres in Norway and Sweden , who had diastolic blood pressure of 100 mm Hg or more . We r and omly assigned patients diltiazem , or diuretics , beta-blockers , or both . The combined primary endpoint was fatal and non-fatal stroke , myocardial infa rct ion , and other cardiovascular death . Analysis was done by intention to treat . FINDINGS Systolic and diastolic blood pressure were lowered effectively in the diltiazem and diuretic and beta-blocker groups ( reduction 20.3/18.7 vs 23.3/18.7 mm Hg ; difference in systolic reduction p<0.001 ) . A primary endpoint occurred in 403 patients in the diltiazem group and in 400 in the diuretic and beta-blocker group ( 16.6 vs 16.2 events per 1000 patient-years ; relative risk 1.00 [ 95 % CI 0.87 - 1.15 ] , p=0.97 ) . Fatal and non-fatal stroke occurred in 159 patients in the diltiazem group and in 196 in the diuretic and beta-blocker group ( 6.4 vs 7.9 events per 1000 patient-years ; 0.80 [ 0.65 - 0.99 ] , p=0.04 ) and fatal and non-fatal myocardial infa rct ion in 183 and 157 patients ( 7.4 vs 6.3 events per 1000 patient-years ; 1.16 [ 0.94 - 1.44 ] , p=0.17 ) . INTERPRETATION Diltiazem was as effective as treatment based on diuretics , beta-blockers , or both in preventing the combined primary endpoint of all stroke , myocardial infa rct ion , and other cardiovascular death BACKGROUND It is unknown whether either the angiotensin-II-receptor blocker irbesartan or the calcium-channel blocker amlodipine slows the progression of nephropathy in patients with type 2 diabetes independently of its capacity to lower the systemic blood pressure . METHODS We r and omly assigned 1715 hypertensive patients with nephropathy due to type 2 diabetes to treatment with irbesartan ( 300 mg daily ) , amlodipine ( 10 mg daily ) , or  placebo .  The target blood pressure was 135/85 mm Hg or less in all groups . We compared the groups with regard to the time to the primary composite end point of a doubling of the base-line serum creatinine concentration , the development of end-stage renal disease , or death from any cause . We also compared them with regard to the time to a secondary , cardiovascular composite end point . RESULTS The mean duration of follow-up was 2.6 years . Treatment with irbesartan was associated with a risk of the primary composite end point that was 20 percent lower than that in the placebo group ( P=0.02 ) and 23 percent lower than that in the amlodipine group ( P=0.006 ) . The risk of a doubling of the serum creatinine concentration was 33 percent lower in the irbesartan group than in the placebo group ( P=0.003 ) and 37 percent lower in the irbesartan group than in the amlodipine group ( P<0.001 ) . Treatment with irbesartan was associated with a relative risk of end-stage renal disease that was 23 percent lower than that in both other groups ( P=0.07 for both comparisons ) . These differences were not explained by differences in the blood pressures that were achieved . The serum creatinine concentration increased 24 percent more slowly in the irbesartan group than in the placebo group ( P=0.008 ) and 21 percent more slowly than in the amlodipine group ( P=0.02 ) . There were no significant differences in the rates of death from any cause or in the cardiovascular composite end point . CONCLUSIONS The angiotensin-II-receptor blocker irbesartan is effective in protecting against the progression of nephropathy due to type 2 diabetes . This protection is independent of the reduction in blood pressure it causes Twenty patients with acute severe hypertension were r and omised to therapy with either nifedipine capsules ( 10 mg ) or captopril tablets ( 25 mg ) given sublingually and the blood pressure recorded for 240 minutes . Oral monotherapy with either agent followed for 3 weeks , then the agents were combined for a further 2 weeks and in the final 6 weeks of the trial a beta-blocker and diuretic were added , if needed . Thirteen patients completed the trial . The major results were : ( i ) nifedipine decreased blood pressure more rapidly than captopril 60 minutes after first ingestion but at 240 minutes equal degrees of fall in blood pressure had been obtained ; ( ii ) neither agent given as sustained monotherapy was able to reduce blood pressure adequately , although nifedipine was better than captopril ; and ( iii ) combination therapy with both agents was conspicuously successful in achieving reduction in blood pressure . It is suggested that combination nifedipine-captopril therapy be subject to a formal trial for early therapy in acute severe hypertension Summary The Syst-Eur Trial is a concerted action of the European Community ’s Medical and Health Research Programme . The trial is carried out in consultation with the World Health Organization , the International Society of Hypertension , the European Society of Hypertension and the World Hypertension League . This article describes the objectives and the protocol of Syst-Eur , a multicentre trial design ed by the European Working Party on High Blood . Pressure in the Elderly ( EWPHE ) , to test the hypothesis that antihypertensive treatment of elderly patients with isolated systolic hypertension results in a significant change in stroke morbidity and mortality . Secondary endpoints include cardiovascular events , such as myocardial infa rct ion and congestive heart failure .  To be eligible patients must be at least 60 years old and have a systolic blood pressure averaging 160–219 mmHg with a diastolic pressure less than 95 mmHg . Patients must give their informed consent and be free of major cardiovascular and non-cardiovascular diseases at entry . The patients are r and omized to active treatment or placebo . Active treatment consists of nitrendipine ( 10–40 mg/day ) , combined with enalapril ( 5–20 mg/day ) and hydrochlorothiazide ( 12.5–25 mg/day ) , as necessary . The patients of the control group receive matching placebos . The drugs ( or matching placebos ) are stepwise titrated and combined in order to reduce systolic blood pressure by 20 mmHg at least to a level below 150 mmHg . Morbidity and mortality are monitored to enable an intention-to-treat and per protocol comparison of the outcome in the 2 treatment groups . A one-year pilot trial ( 1989 ) showed that the protocol is practicable . The Ethics Committee therefore decided to start the definite study ( 1990 ) , in which r and omized patients will be followed for 5 years . Recruitment of new centres and of the required 3,000 patients will last 3 years ( until 1993 ) OBJECTIVE ACE inhibitors and calcium antagonists may favorably affect serum lipids and glucose metabolism . The primary aim of the Fosinopril Versus Amlodipine Cardiovascular Events R and omized Trial ( FACET ) was to compare the effects of fosinopril and amlodipine on serum lipids and diabetes control in NIDDM patients with hypertension . Prospect ively defined cardiovascular events were assessed as secondary outcomes . RESEARCH DESIGN AND METHODS Inclusion criteria included a diagnosis of NIDDM and hypertension ( systolic blood pressure of > 140 mmHg or diastolic blood pressure of > 90 mmHg ) . Exclusion criteria included a history of coronary heart disease or stroke , serum creatinine > 1.5 mg/dl , albuminuria > 40 μg/min , and use of lipid-lowering drugs , aspirin , or antihypertensive agents other than beta-blockers or diuretics . A total of 380 hypertensive diabetics were r and omly assigned to open-label fosinopril ( 20 mg/day ) or amlodipine ( 10 mg/day ) and followed for up to 3.5 years . If blood pressure was not controlled , the other study drug was added . RESULTS Both treatments were effective in lowering blood pressure . At the end of followup , between the two groups there was no significant difference in total serum cholesterol , HDL cholesterol , HbA1c , fasting serum glucose , or plasma insulin . The patients receiving fosinopril had a significantly lower risk of the combined outcome of acute myocardial infa rct ion , stroke , or hospitalized angina than those receiving amlodipine ( 14/189 vs. 27/191 ; hazards ratio = 0.49 , 95 % CI = 0.26–0.95 ) . CONCLUSIONS Fosinopril and amlodipine had similar effects on biochemical measures , but the patients r and omized to fosinopril had a significantly lower risk of major vascular events , compared with the patients r and omized to amlodipine Background —Most cardiovascular events associated with hypertension are complications of atherosclerosis . Some antihypertensive agents influence experimental models of atherosclerosis through mechanisms independent of blood pressure lowering . Methods and Results —The European Lacidipine Study on Atherosclerosis ( ELSA ) was a r and omized , double-blind trial in 2334 patients with hypertension that compared the effects of a 4-year treatment based on either lacidipine or atenolol on an index of carotid atherosclerosis , the mean of the maximum intima-media thicknesses ( IMT ) in far walls of common carotids and bifurcations ( CBMmax ) . This index has been shown by epidemiological studies to be predictive of cardiovascular events . A significant ( P < 0.0001 ) effect of lacidipine was found compared with atenolol , with a treatment difference in 4-year CBMmax progression of −0.0227 mm ( intention-to-treat population ) and −0.0281 mm ( completers ) . The yearly IMT progression rate was 0.0145 mm/y in atenolol-treated and 0.0087 mm/y in lacidipine-treated patients ( completers , 40 % reduction;P = 0.0073 ) . Patients with plaque progression were significantly less common , and patients with plaque regression were significantly more common in the lacidipine group . Clinic blood pressure reductions were identical with both treatments , but 24-hour ambulatory systolic/diastolic blood pressure changes were greater with atenolol ( −10/−9 mm Hg ) than with lacidipine ( −7/−5 mm Hg ) . No significant difference between treatments was found in any cardiovascular events , although the relative risk for stroke , major cardiovascular events , and mortality showed a trend favoring lacidipine . Conclusion —The greater efficacy of lacidipine  on carotid IMT progression and number of plaques per patient , despite a smaller ambulatory blood pressure reduction , indicates an antiatherosclerotic action of lacidipine independent of its antihypertensive action BACKGROUND The efficacy of new antihypertensive drugs has been question ed . We compared the effects of conventional and newer antihypertensive drugs on cardiovascular mortality and morbidity in elderly patients . METHODS We did a prospect i ve , r and omised trial in 6614 patients aged 70 - 84 years with hypertension ( blood pressure > or = 180 mm Hg systolic , > or = 105 mm Hg diastolic , or both ) . Patients were r and omly assigned conventional antihypertensive drugs ( atenolol 50 mg , metoprolol 100 mg , pindolol 5 mg , or hydrochlorothiazide 25 mg plus amiloride 2.5 mg daily ) or newer drugs ( enalapril 10 mg or lisinopril 10 mg , or felodipine 2.5 mg or isradipine 2 - 5 mg daily ) . We assessed fatal stroke , fatal myocardial infa rct ion , and other fatal cardiovascular disease . Analysis was by intention to treat . FINDINGS Blood pressure was decreased similarly in all treatment groups . The primary combined endpoint of fatal stroke , fatal myocardial infa rct ion , and other fatal cardiovascular disease occurred in 221 of 2213 patients in the conventional drugs group ( 19.8 events per 1000 patient-years ) and in 438 of 4401 in the newer drugs group ( 19.8 per 1000 ; relative risk 0.99 [ 95 % CI 0.84 - 1.16 ] , p=0.89 ) . The combined endpoint of fatal and non-fatal stroke , fatal and non-fatal myocardial infa rct ion , and other cardiovascular mortality occurred in 460 patients taking conventional drugs and in 887 taking newer drugs ( 0.96 [ 0.86 - 1.08 ] , p=0.49 ) . INTERPRETATION Old and new antihypertensive drugs were similar in prevention of cardiovascular mortality or major events . Decrease in blood pressure was of major importance for the prevention of cardiovascular events CONTEXT Hypertension is a leading cause of end-stage renal disease ( ESRD ) in the United States , with no known treatment to prevent progressive declines leading to ESRD . OBJECTIVE To compare the effects of 2 levels of blood pressure ( BP ) control and 3 antihypertensive drug classes on glomerular filtration rate ( GFR ) decline in hypertension . DESIGN R and omized 3 x 2 factorial trial with enrollment from February 1995 to September 1998 . SETTING AND PARTICIPANTS A total of 1094 African Americans aged 18 to 70 years with hypertensive renal disease ( GFR , 20 - 65 mL/min per 1.73 m(2 ) ) were recruited from 21 clinical centers throughout the United States and followed up for 3 to 6.4 years . INTERVENTIONS Participants were r and omly assigned to 1 of 2 mean arterial pressure goals , 102 to 107 mm Hg ( usual ; n = 554 ) or 92 mm Hg or less ( lower ; n = 540 ) , and to initial treatment with either a beta-blocker ( metoprolol 50 - 200 mg/d ; n = 441 ) , an angiotensin-converting enzyme inhibitor ( ramipril 2.5 - 10 mg/d ; n = 436 ) or a dihydropyridine calcium channel blocker , ( amlodipine 5 - 10 mg/d ; n = 217 ) . Open-label agents were added to achieve the assigned BP goals . MAIN OUTCOME MEASURES Rate of change in GFR ( GFR slope ) ; clinical composite outcome of reduction in GFR by 50 % or more ( or > or = 25 mL/min per 1.73 m2 ) from baseline , ESRD , or death . Three primary treatment comparisons were specified : lower vs usual BP goal ; ramipril vs metoprolol ; and amlodipine vs metoprolol . RESULTS Achieved BP averaged ( SD ) 128/78 ( 12/8 ) mm Hg in the lower BP group and 141/85 ( 12/7 ) mm Hg in the usual BP group . The mean ( SE ) GFR slope from baseline through 4 years did not differ significantly between the lower BP group ( -2.21 [ 0.17 ] mL/min per 1.73 m2 per year ) and the usual BP group ( -1.95 [ 0.17 ] mL/min per 1.73 m2 per year ; P = .24 ) , and the lower BP goal did not significantly reduce the rate of the clinical composite outcome ( risk reduction for lower BP group = 2 % ; 95 % confidence interval [ CI ] , -22 % to 21 % ; P = .85 ) . None of the drug group comparisons showed consistent significant differences in the GFR slope . However , compared with the metoprolol and amlodipine groups , the ramipril group manifested risk reductions in the clinical composite outcome of 22 % ( 95 % CI , 1%-38 % ; P = .04 ) and 38 % ( 95 % CI , 14%-56 % ; P = .004 ) , respectively . There was no significant difference in the clinical composite outcome between the amlodipine and metoprolol groups . CONCLUSIONS No additional benefit of slowing progression of hypertensive nephrosclerosis was observed with the lower BP goal . Angiotensin-converting enzyme inhibitors appear to be more effective than beta-blockers or dihydropyridine calcium channel blockers in slowing GFR decline BACKGROUND The Valsartan Antihypertensive Long-term Use Evaluation ( VALUE ) trial was design ed to test the hypothesis that for the same blood-pressure control , valsartan would reduce cardiac morbidity and mortality more than amlodipine in hypertensive patients at high cardiovascular risk . METHODS 15?245 patients , aged 50 years or older with treated or untreated hypertension and high risk of cardiac events participated in a r and omised , double-blind , parallel-group comparison of therapy based on valsartan or amlodipine . Duration of treatment was event-driven and the trial lasted until at least 1450 patients had reached a primary endpoint , defined as a composite of cardiac mortality and morbidity .  Patients from 31 countries were followed up for a mean of 4.2 years . FINDINGS Blood pressure was reduced by both treatments , but the effects of the amlodipine-based regimen were more pronounced , especially in the early period ( blood pressure 4.0/2.1 mm Hg lower in amlodipine than valsartan group after 1 month ; 1.5/1.3 mm Hg after 1 year ; p<0.001 between groups ) . The primary composite endpoint occurred in 810 patients in the valsartan group ( 10.6 % , 25.5 per 1000 patient-years ) and 789 in the amlodipine group ( 10.4 % , 24.7 per 1000 patient-years ; hazard ratio 1.04 , 95 % CI 0.94 - 1.15 , p=0.49 ) . INTERPRETATION The main outcome of cardiac disease did not differ between the treatment groups . Unequal reductions in blood pressure might account for differences between the groups in cause-specific outcomes . The findings emphasise the importance of prompt blood-pressure control in hypertensive patients at high cardiovascular risk BACKGROUND Antihypertensive drugs may differ in their ability to reduce LV mass . Covariates other than drug selection , such as pretreatment LV mass , body weight , the magnitude of blood pressure reduction , race , and age may modify the response of LV mass to therapy . METHODS AND RESULTS Patients with mild to moderate hypertension ( diastolic blood pressure , 95 to 109 mm Hg ) were r and omly allocated to treatment with atenolol , captopril , clonidine , diltiazem , hydrochlorothiazide , or prazosin in a double-masked trial . Patients achieving the goal diastolic blood pressure of < 90 mm Hg during drug titration entered a 1-year maintenance period . Longitudinal analysis examined changes from baseline echocardiogram in LV mass at 8 weeks and at 1 year , statistically adjusted for pretreatment LV mass , systolic blood pressure , body weight , sodium excretion , physical activity , race , and age . Significant reductions at 1 year in adjusted LV mass were seen for patients in the highest tertile of pretreatment LV mass treated with hydrochlorothiazide ( mean , -42.9 ; 95 % confidence limits , -65.5 , -20.2 g ) , captopril ( mean , -38.7 ; 95 % confidence limits , -61.0 , -16.4 g ) , and atenolol ( mean , -28.1 ; 95 % confidence limits , -50.9 , -5.3 g ) . These treatment effects differed from those of prazosin , diltiazem , or clonidine . CONCLUSIONS Antihypertensive drugs have disparate effects on LV mass independent of the magnitude of blood pressure reduction . Patients with adequate blood pressure control on captopril , hydrochlorothiazide , and atenolol show a reduction of LV mass after 1 year of treatment , whereas patients on diltiazem , clonidine , or prazosin do not BACKGROUND There is a pressing clinical requirement for an early simple test of severity in acute pancreatitis . We investigated the use of an assay of trypsinogen activation peptide ( TAP ) . METHODS We undertook a multicentre study in 246 patients ( 172 with acute pancreatitis [ 35 with severe disease ] , 74 controls ) . We assessed the predictive value of urinary TAP concentrations measured by a vali date d competitive immunoassay . We compared the results with those for plasma C-reactive protein and three clinicobiochemical scoring systems . TAP and C-reactive protein concentrations were analysed at set times after symptom onset and compared with the clinicobiochemical systems scores at key times during hospital stay . FINDINGS At 24 h after symptom onset , the median urinary TAP concentration was 37 nmol/L ( IQR 17 - 110 ) for severe and 15 nmol/L ( 5 - 35 ) for mild disease ( p<0.001 ) . The respective values for plasma C-reactive protein were 24 mg/L ( 3 - 34 ) and 25 mg/L ( 6 - 75 ; p=0.208 ) . The sensitivity , specificity , positive predictive , and negative predictive values of the test to show severe acute pancreatitis compared with mild acute pancreatitis at 24 h were : for TAP ( > 35 nmol/L ) , 58 % , 73 % , 39 % , and 86 % , respectively , and for C-reactive protein ( > 150 mg/L ) , 0 % , 90 % , 0 % , and 75 % . 48 h after admission the values for the clinicobiochemical scoring systems were : APACHE II ( > or = 8) , 56 % , 64 % , 30 % , and 85 % ; Ranson score ( > or = 3 ) , 89 % , 64 % , 38 % , and 96 % ; and Glasgow score ( > or = 3 ) , 77 % , 75 % , 44 % , and 93 % . At 48 h , the values for C-reactive protein were 86 % , 61 % , 37 % , and 94 % and for TAP were 83 % , 72 % , 44 % , and 94 % . Combined testing of C-reactive protein and TAP was not superior to TAP alone for accuracy . INTERPRETATION Urinary TAP provided accurate severity prediction 24 h after onset of symptoms . This single marker of severity in acute pancreatitis deserves routine clinical application It is well established that hypertensive patients benefit from drug treatment of their disorder . In recent years three major out-come studies of antihypertensive treatment in elderly hypertensives have shown substantial benefits , i.e. a reduction in the risk of stroke and other cardiovascular mortality and morbidity . In all these studies beta-blockers and /or diuretics were used in comparison with placebo . Newer therapeutic alternatives have , however , at least theoretically , many advantages which could result in further improvements in prognosis . The initial Swedish Trial in Old Patients with Hypertension ( STOP-Hypertension 1 ) was conducted in men and women aged 70 - 84 years . STOP-Hypertension 2 will evaluate the therapy used in STOP-Hypertension 1 against therapy based on either ACE-inhibitors ( enalapril and lisinopril ) or on calcium antagonists ( isradipine and felodipine ) , using the PROBE design ( Prospect i ve , R and omised , Open , Blinded Endpoint evaluation ) . The primary aim will be to assess the effect on cardiovascular mortality . Statistical calculations indicate that 6,600 patients , followed for four years will be needed ( 2p < 0.05 , power 90 % ) to obtain significance if there is a 25 % difference between the new and the established therapy . Patients in primary health care ( 300 centres ) will be included if their supine blood pressure is > or = 180/105 mmHg ( and /or ) . Recruitment of patients started in September 1992 and so far more than 100 patients /week have been included OBJECTIVES We sought to determine the efficacy of isradipine in reducing left ventricular ( LV ) mass and wall thickness in hypertensive patients . BACKGROUND LV hypertrophy on the echocardiogram is a strong predictor of cardiovascular events . Reduction of LV mass may be a desirable goal of drug therapy for hypertension . However , although thiazide diuretic drugs have been advocated as first-line therapy for hypertension , their efficacy in reducing LV mass has been question ed . METHODS Patients with mild to moderate diastolic hypertension and LV mass in excess of 1 SD of normal values were r and omized to isradipine ( n = 89 ) or hydrochlorothiazide therapy ( n = 45 ) . Evaluations were obtained at baseline , after 3 and 6 months of treatment and 2 weeks after treatment was stopped . RESULTS At 6 months , LV mass decreased by 43 + /- 45 g ( mean + /- SD ) with hydrochlorothiazide ( p < 0.001 ) but only by 11 + /- 48 g with isradipine ( p = NS ; between-group comparison , p < 0.001 ) . Two weeks after drug therapy was stopped , LV mass remained 24 + /- 41 g lower than that at baseline in the hydrochlorothiazide group ( p = 0.003 ) but only 7 + /- 50 g lower in the isradipine group ( p = NS ) . Septal and posterior wall thicknesses were significantly and equally reduced with both isradipine and hydrochlorothiazide . Greater LV mass reduction with hydrochlorothiazide was related to a 2.8 + /- 3.3-mm reduction of LV cavity size with hydrochlorothiazide but no reduction with isradipine . At 6 months of treatment , diastolic blood pressure ( BP ) by design was equally reduced in both treatment groups . At 3 months , systolic BP was reduced by 17 + /- 15 mm Hg with isradipine and by 26 + /- 15 and 25 + /- 17 mm Hg at 3 and 6 months , respectively , with hydrochlorothiazide ( p = 0.003 , between-group comparison ) . However , on stepwise multivariable regression analysis , treatment selection ( partial r2 = 0.082 , p = 0.001 ) , change in average 24-h systolic BP ( partial r2 = 0.032 , p = 0.029 ) and change in average sitting systolic BP ( partial r2 = 0.017 , p = 0.096 ) were predictive of LV mass reduction . CONCLUSIONS Despite an equivalent reduction of diastolic BP , 6 months of therapy with hydrochlorothiazide is associated with a substantial reduction of LV mass , greater than that with isradipine . The superior efficacy of hydrochlorothiazide for LV mass reduction is associated with a greater reduction of systolic BP as well as drug selection itself . These data may have important therapeutic implication BACKGROUND Angiotensin-converting-enzyme inhibitors improve the outcome among patients with left ventricular dysfunction , whether or not they have heart failure . We assessed the role of an angiotensin-converting-enzyme inhibitor , ramipril , in patients who were at high risk for cardiovascular events but who did not have left ventricular dysfunction or heart failure . METHODS A total of 9297 high-risk patients ( 55 years of age or older ) who had evidence of vascular disease or diabetes plus one other cardiovascular risk factor and who were not known to have a low ejection fraction or heart failure were r and omly assigned to receive ramipril ( 10 mg once per day orally ) or matching placebo for a mean of five years . The primary outcome was a composite of myocardial infa rct ion , stroke , or death from cardiovascular causes . The trial was a two-by-two factorial study evaluating both ramipril and vitamin E. The effects of vitamin E are reported in a companion paper . RESULTS A total of 651 patients who were assigned to receive  ramipril ( 14.0 percent ) reached the primary end point , as compared with 826 patients who were assigned to receive placebo ( 17.8 percent ) ( relative risk , 0.78 ; 95 percent confidence interval , 0.70 to 0.86 ; P<0.001 ) . Treatment with ramipril reduced the rates of death from cardiovascular causes ( 6.1 percent , as compared with 8.1 percent in the placebo group ; relative risk , 0.74 ; P<0.001 ) , myocardial infa rct ion ( 9.9 percent vs. 12.3 percent ; relative risk , 0.80 ; P<0.001 ) , stroke ( 3.4 percent vs. 4.9 percent ; relative risk , 0.68 ; P<0.001 ) , death from any cause ( 10.4 percent vs. 12.2 percent ; relative risk , 0.84 ; P=0.005 ) , revascularization procedures ( 16.3 percent vs. 18.8 percent ; relative risk , 0.85 ; P<0.001 ) , cardiac arrest ( 0.8 percent vs. 1.3 percent ; relative risk , 0.62 ; P=0.02 ) , [ corrected ] heart failure ( 9.1 percent vs. 11.6 percent ; relative risk , 0.77 ; P<0.001 ) , and complications related to diabetes ( 6.4 percent vs. 7.6 percent ; relative risk , 0.84 ; P=0.03 ) . CONCLUSIONS Ramipril significantly reduces the rates of death , myocardial infa rct ion , and stroke in a broad range of high-risk patients who are not known to have a low ejection fraction or heart failure Essential hypertension is a major Public Health issue . Although the number of treated hypertensive patients has increased , only 25 % of treated patients have their blood pressure levels under control . The benefit of treating hypertension has been proven , but cardiovascular morbidity and mortality rates remain high . The ideal antihypertensive drug should not only normalize blood pressure levels , but also reduce the associated cardiovascular morbidity and mortality rates . The role of angiotensin II in systemic hypertension and its complications has been recently redefined . The potent trophic effects of angiotensin II on blood vessels and on cardiac cells have been well demonstrated , especially the role of angiotensin II in left ventricular hypertrophy , vascular hypertrophy , endothelial dysfunction , and congestive heart failure . Of all ongoing mortality and morbidity trials in systemic hypertension , VALUE ( Valsartan Antihypertensive Long-term Use Evaluation ) is the only one comparing an angiotensin II antagonist ( valsartan ) with a third-generation calcium channel blocker ( amlodipine ) . The main hypothesis of the VALUE trial is that , for an equivalent decrease in blood pressure , valsartan will be more effective than amlodipine in decreasing cardiac mortality and morbidity . VALUE is a prospect i ve , multinational , multicentre , double-blind , r and omized , active-controlled , 2-arm parallel group comparison with a response-dependent dose titration scheme . VALUE involves 14,400 patients in over 30 countries , who will be followed for 4 years or until 1450 patients experience a primary endpoint . The population to be included in VALUE consists of hypertensive men and women , aged 50 years or older , and at a relatively high risk of sustaining a cardiovascular event . The high risk profile is defined taking into account age , gender , and a list of cardiovascular risk factors and disease factors . Risk factors are cigarette smoking , hypercholesterolaemia , diabetes mellitus , uncomplicated left ventricular hypertrophy , proteinuria , and high serum creatinine . Disease factors include documented history of myocardial infa rct ion , peripheral vascular disease , stroke or transient ischaemic attack , or the presence of left ventricular hypertrophy with strain on the ECG . A unique feature of VALUE is the assessment of the predictive power of this cardiovascular risk factor scale in a large population of treated hypertensive patients . The trial started on 10 September 1997 Objective : Our aim was to compare the effect of lacidipine and chlorthalidone on cardiovascular outcome as a primary parameter and blood pressure as a secondary in elderly patients with isolated systolic hypertension in a prospect i ve study with an open design . Methods : 1882 males and females out patients ≥60 years were r and omly assigned to the administration of  chlorthalidone 12.5 mg o.d . or lacidipine 4 mg o.d . Patients were recruited if sitting systolic blood pressure was ≥160 mmHg with a diastolic blood pressure equal or lower than 95 mmHg .  Primary endpoint was a composite of cardiovascular and cerebrovascular events . Results : At r and omization mean systolic blood pressure was 178.1 mmHg in the lacidipine and 178.2 mmHg in the chlorthalidone group , the corresponding mean diastolic values being 86.9 and 86.8 mmHg . In both lacidipine and chlorthalidone groups treatment caused a significant ( p < 0.001 ) and marked systolic blood pressure reduction which was maintained throughout the treatment period with a significant ( p < 0.001 ) and steady although less marked reduction in diastolic blood pressure as well . At the end of treatment period ( median 32 months ) , the reduction was 36.8/8.1 mmHg ( systolic/diastolic ) in the chlorthalidone and 38.4/7.9 mmHg in the lacidipine group , the final on treatment blood pressures being 142.0/79.2 and 143.2/79.5 mmHg , respectively . Treatments were similarly effective in males and females and in age groups between 60 and 69 years ( n = 763 ) , 70 and 79 years ( n = 744 ) and ≥80 years ( n = 375 ) . Similar reductions were obtained in a subgroup of patients ( n = 209 ) followed in double-blind fashion for 1 year . The overall incidence of the primary endpoints was 9.3 % with no significant between-group difference . Total mortality was also similar between groups . Conclusions : In elderly patients with isolated systolic hypertension , administration of lacidipine or chlorthalidone markedly reduced systolic blood pressure with no difference in the incidence of cardiovascular events and total mortality BACKGROUND It has recently been reported that the use of calcium-channel blockers for hypertension may be associated with an increased risk of cardiovascular complications . Because this issue remains controversial , we studied the incidence of such complications in patients with non-insulin-dependent diabetes mellitus and hypertension who were r and omly assigned to treatment with either the calcium-channel blocker nisoldipine or the angiotensin-converting-enzyme inhibitor enalapril as part of a larger study . METHODS The Appropriate Blood Pressure Control in Diabetes ( ABCD ) Trial is a prospect i ve , r and omized , blinded trial comparing the effects of moderate control of blood pressure ( target diastolic pressure , 80 to 89 mm Hg ) with those of intensive control of blood pressure ( diastolic pressure , 75 mm Hg ) on the incidence and progression of complications of diabetes . The study also compared nisoldipine with enalapril as a first-line antihypertensive agent in terms of the prevention and progression of complications of diabetes . In the current study , we analyzed data on a secondary end point ( the incidence of myocardial infa rct ion ) in the subgroup of patients in the ABCD Trial who had hypertension . RESULTS Analysis of the 470 patients in the trial who had hypertension ( base-line diastolic blood pressure , > or = 90 mm Hg ) showed similar control of blood pressure , blood glucose and lipid concentrations , and smoking behavior in the nisoldipine group ( 237 patients ) and the enalapril group ( 233 patients ) throughout five years of follow-up . Using a multiple logistic-regression model with adjustment for cardiac risk factors , we found that nisoldipine was associated with a higher incidence of fatal and nonfatal myocardial infa rct ions ( a total of 24 ) than enalapril ( total , 4 ) ( risk ratio , 9.5 ; 95 percent confidence interval , 2.7 to 33.8 ) . CONCLUSIONS In this population of patients with diabetes and hypertension , we found a significantly higher incidence of fatal and nonfatal myocardial infa rct ion among those assigned to therapy with the calcium-channel blocker nisoldipine than among those assigned to receive enalapril . Since our findings are based on a secondary end point , they will require confirmation Objective : A case control study has reported a 60 % higher risk of myocardial infa rct ion in hypertensives treated with a calcium channel blocker ( CCB ) . We examined the Department of Health Hypertension Care Computing Project ( DHCCP ) data to see if we could confirm or refute this suggestion . Design : Two case control studies , matched and unmatched , plus two longitudinal studies from 1 year of presentation , one for all subjects given a CCB  for more than 1 year compared with those not given this drug , and the second comparing survival on the different drugs initially given between 3 and 12 months of follow-up . Subjects : A total of 9328 subjects were included in the analyses and 2154 died . Of these , 6406 received one or more of the following index drugs : 26 % a calcium channel blocker ( CCB ) ; 84 % a diuretic ; 29 % alpha methyldopa ; 12 % a beta-blocker ( BB ) ; and 11 % an angiotensin-converting enzyme ( ACE ) inhibitor . The CCBs were nifedipine , diltiazem or verapamil . Results : In the case control studies a group given diuretics ± other treatments ( but not including one of the index drugs ) provided a reference group with a relative risk ( RR ) of 1.0 . In the matched case control study the adjusted RR for a CCB  without a diuretic was 1.32 ( 95 % CI 0.64–2.70 ) for IHD mortality and 1.05 ( 95 % CI 0.60–1.84 ) for cardiovascular mortality . Similar results were observed for methyldopa , BBs and ACE inhibitors . The results in the unmatched case control analysis were also similar . The longitudinal study comparing all those treated for over 1 year with a CCB with all other treatments showed a RR for total mortality of 1.03 ( 95 % CI 0.85–1.25 ) . The longitudinal study of total mortality according to treatment initiated at 3–12 months found results of a similar magnitude for CCBs , methyldopa and BBs . Conclusions : The reference diuretic group had less severe cardiovascular disease than other groups . Treatment with a CCB , BB or methyldopa was associated with an excess mortality in comparison with this reference group . The excess was similar in the different drug groups Context Previously published results of this r and omized , double-blind trial showed that high-risk patients with type 2 diabetic nephropathy had better renal protection if they were treated with irbesartan rather than amlodipine in addition to conventional antihypertensive therapy . Contribution These detailed analyses showed no differences in overall cardiovascular outcomes between patients given irbesartan or amlodipine .  Fewer patients given irbesartan had heart failure and fewer patients given amlodipine had heart attacks . Caution s The trial had limited power to detect important differences between groups in mortality or strokes , and most patients received several antihypertensive agents . The Editors Patients with diabetes have an increased risk for cardiovascular complications and death ( 1 ) . Studies that analyzed the effects of inhibition of the reninangiotensin system on the risk for cardiovascular complications included a substantial number of patients with diabetes ( 2 - 5 ) or were done exclusively in patients with diabetes ( 6 - 8 ) . The meta- analysis of these studies ( 9 ) , the analysis of the diabetic cohorts in the Heart Outcomes Prevention Evaluation ( HOPE ) study ( 2 ) , and the Losartan Intervention for Endpoint Reduction in Hypertension ( LIFE ) trial ( 5 ) demonstrated that angiotensin-converting enzyme ( ACE ) inhibitors ( 2 , 9 ) and angiotensin-receptor blockers ( 5 ) had a statistically significant advantage over placebo or alternative agents in decreasing the risk for several cardiovascular events . These studies r and omly assigned few patients with renal involvement and overt proteinuria . Overt proteinuria occurred in fewer than 20 % of the 470 patients in the Appropriate Blood Pressure Control in Diabetes ( ABCD ) trial ( 6 ) , and only 11 % of the 1195 patients in the LIFE trial ( 5 ) . The Captopril Prevention Project ( CAPP ) ( 3 ) and the Swedish Trial in Old Patients with Hypertension-2 ( STOP Hypertension-2 ) ( 4 ) did not state the number of patients with diabetes and overt proteinuria . There were no such patients in the Fosinopril versus Amlodipine Cardiovascular Events Trial ( FACET ) ( 7 ) , and patients with dipstick-positive albuminuria were excluded from the HOPE trial ( 2 ) . Since proteinuria is an independent risk factor for cardiovascular disease ( 10 , 11 ) , the data obtained in the aforementioned trials can not be extrapolated to patients with type 2 diabetes and overt nephropathy . Trials performed in such patients have reported a blood pressureindependent effect of two different angiotensin-receptor blocker agents to protect against nephropathy ( 12 , 13 ) without a change in all-cause mortality . Apart from studies in heart failure , few cardiovascular data exist for receptor blockers compared with either placebo or calcium-channel blockers . We report on the analysis of the cardiovascular end points that were monitored as secondary end points in the Irbesartan Diabetic Nephropathy Trial ( IDNT ) ( 12 ) and assess whether an angiotensin II receptor blocker or a calcium-channel blocker alters the risk for cardiovascular events beyond those observed by blood pressure reduction alone without such agents . Methods Patients The IDNT was a r and omized , double-blind study on the effect of treatment with irbesartan or amlodipine compared with placebo in patients with type 2 diabetic nephropathy . The protocol of this study has been published ( 12 , 14 ) . Entry criteria required that patients be between 30 and 70 years of age and have type 2 diabetes mellitus and overt nephropathy , as evidence d by current treatment for hypertension or by a protein excretion rate of 900 mg/d or greater , serum creatinine level of 89 mol/L ( 1.0 mg/dL ) to 266 mol/L ( 3.0 mg/dL ) in women or of 106 mol/L ( 1.2 mg/dL ) to 266 mol/L ( 3.0 mg/dL ) in men , and baseline seated blood pressure greater than 135/85 mm Hg . The institutional review boards of each center approved the protocol . All patients gave written informed consent . Treatment and R and omization Patients were r and omly assigned central ly by computer to receive treatment with irbesartan , 300 mg/d ( Avapro , Bristol-Myers Squibb , Princeton , New Jersey ) ; amlodipine , 10 mg/d ( Norvasc , Pfizer , New York ) ; or matched placebo . To minimize any center effect , r and omization was blocked by center . All patients had blood pressure controlled to the same blood pressure goal of less than 135/85 mm Hg by using antihypertensive agents other than ACE inhibitors , angiotensin II receptor blocking agents , or calcium-channel blockers . For the analysis of cardiovascular end points , patients were followed to initiation of treatment for end-stage renal failure ( dialysis or renal transplantation ) , reaching a serum creatinine level of 530.4 mol/L ( 6.0 mg/dL ) or higher , death , or administrative censoring in December 2000 . Outcomes We prospect ively established cardiovascular outcomes , defined in the Appendix Table . Appendix Table . Classification for Fatal and Nonfatal Cardiovascular Events Ascertainment of Cardiovascular Events Information about hospitalizations and adverse events were screened at Bristol-Myers Squibb , Princeton , New Jersey , by trained , blinded clinical research associates to identify potential cardiovascular events . Investigators used study forms to report and characterize all cardiovascular outcomes . For all potential events , records , including laboratory values , electrocardiograms , and radiographic reports were obtained for clarification . Since myocardial infa rct ions may go unrecognized , a central electrocardiogram reading center was established at Brigham and Women 's Hospital , Boston , Massachusetts , where two cardiologists review ed every electrocardiogram . Electrocardiography was performed at baseline , 6 months , 12 months , and annually thereafter . A total of 5698 electrocardiograms were review ed at the center . When a new Q-wave infa rct ion was found , the cardiologists asked whether a clinical myocardial infa rct ion was reported . Even when myocardial infa rct ions were not clinical ly reported , these Q-wave infa rct ions were adjudicated as myocardial infa rct ions . Adjudication of Cardiovascular Events Investigators at each center reported cardiovascular events , defined in the Appendix Table . The information on all potential events was referred to one member of the Outcomes Confirmation and Classification Committee ( Appendix ) . If the committee member agreed with the judgment of the center investigator , their combined judgment was accepted . If the center investigator and the committee member differed , the case material was review ed by the membership of the committee , whose decision was accepted . Deaths were adjudicated by a Mortality Committee ( Appendix ) . Each death was review ed by two members of the committee and presented to the membership , whose decision was accepted as final . Statistical Analysis For graphical presentation ( Figure ) and overall testing for statistically significant differences among the three treatment groups , time to the first occurrence of either a specific cardiovascular outcome or one of the composite outcomes was analyzed by product-limit survival curves and the log-rank test ( 15 ) . We used proportional hazards modeling to determine hazard ratios . For the cardiovascular death outcome , which could occur only once , we used the st and ard proportional hazards model ( 16 ) , with treatment assignment as the only independent covariate . For other cardiovascular outcomes , which could occur more than once , we used the And ersonGill formulation of the proportional hazards model ( 17 ) , in which patients are considered at risk for the first event from r and omization to the first event , at risk for the second event from the day following the first event to the second event , and so forth , permitting use of all the data . In accordance with the method of Lee and colleagues ( 18 ) , we used a robust variance estimate that accounts for the possibility of correlation of risk for several events within a patient . We believed that occurrence of a first event of a given type increases the likelihood of a subsequent similar event . Therefore , both treatment assignment and a time-dependent covariate indicating whether the event was the first of its type or a subsequent event were included in these analyses . The time-dependent covariate was statistically significant in each case , confirming the above assumption . There was no statistically significant interaction between treatment and the time-dependent covariatethe effects of treatment assignment were similar for first and subsequent events and inclusion of the time-dependent covariate did not change either the estimates of the treatment effect or their statistical significance s. Figure . Time to first cardiovascular composite event as a function of treatment assignment . P Data management and computations were done by using SAS software for Windows , version 8 ( SAS Institute , Inc. , Cary , North Carolina ) , or S-Plus for Windows , version 6.0 ( Insightful Corp. , Seattle , Washington ) . Statistical tests were two sided . A P value of 0.05 or less , unadjusted for the multiple comparisons , was considered statistically significant . Role of the Funding Sources The funding sources were involved in the data collection but not in the analysis or interpretation or the decision to su bmi t the manuscript for publication . Results The baseline characteristics of the three groups are shown in Table 1 . A flow diagram of the study is shown in the Appendix Figure . Table 1 . Baseline Characteristics Appendix Figure . Flow diagram for the Irbesartan Diabetic Nephropathy Trial . Clinical Management During the study , the blood pressure decreased from the baseline values to 140/77 mm Hg in the irbesartan group , 141/77 mm Hg in the amlodipine group , and 144/80 mm Hg in the placebo group . Blood pressure in the two active treatment groups did not differ ; values in both groups were statistically significantly lower than in the placebo group ( P = 0.001 ) . The distribution of non study drugs used to achieve the target blood pressure was similar A multicenter , r and omized , controlled , double-blind U.S. trial is comparing the combined effects of diet treatment and 1 of 5 active drug regimens with diet treatment alone , for the long-term management of middle-aged adults with " mild " hypertension . Factors stimulating this trial are data documenting the high prevalence of mild hypertension in the adult population ; mild hypertension 's responsibility for a high proportion of morbidity and mortality attributable to hypertension overall ; data from long-term hypertension intervention trials showing reduced morbidity and mortality of people with mild hypertension with use of either diuretics or beta blockers as step-1 therapy , and other trials that failed to demonstrate beneficial impact on morbidity and mortality , possibly due to residual questions concerning aspects of benefit to risk ratios with these medications ; recent data from trials showing long-term control of mild hypertension and other risk factors by nutritional means ; lack of data from long-term trials on benefit to risk ratios with newer drugs such as selective alpha 1 inhibitors , angiotensin converting enzyme inhibitors and calcium channel blockers ; paucity of data from trials on long-term combined effects of diet and drug therapy , and of diet alone , for people with mild hypertension . During the next few years , phase 1 of the trial will study 6 groups of drugs . The step-1 drugs are angiotensin converting enzyme inhibitor ( enalapril ) , alpha 1 inhibitor ( doxazosin ) , beta blocker ( acebutolol ) , calcium channel blocker ( amlodipine ) , diuretic ( chlorthalidone ) and placebo . All participants are to receive vigorous sustained nutritional counseling to reduce obesity , moderate sodium intake and avoid heavy use of alcohol . Key endpoints for phase 1 of the study are the need for additional medication to control mild hypertension , side effects ( i.e. , clinical and biochemical ) and consequent need to discontinue drug and quality of life . Phase-1 data are to be used to complete the phase-2 design , with the ultimate aim to assess effects on morbidity and mortality A single-center , prospect i ve double-blind r and omized trial was conducted to compare the efficacy and safety of the calcium channel blocker nisoldipine in a sustained release coat-core formulation ( CC ) , titrated from 10 mg to 40 mg daily , with the angiotensin converting enzyme inhibitor enalapril , titrated from 10 to 40 mg daily , in the treatment of black South African patients with severe hypertension ( sitting diastolic blood pressure [ DBP ] between 115 and 140 mm Hg , confirmed by 24-h ambulatory blood pressure monitoring ) . Treatment target was a sitting DBP < 95 mm Hg by the 9th week of treatment . This was followed by a 4-month open phase using nisoldipine CC 10 to 60 mg daily . Ninety-six patients had complete data at baseline , and at the end of the double-blind and open phases , and were included in this analysis . In both groups , all patients required titration up to the maximal dose of double-blind medication . Monotherapy with nisoldipine CC , but not enalapril , significantly reduced both sitting and 24-h ambulatory blood pressure ( BP ) . Twenty-four-hour BP in the nisoldipine CC group decreased from 179+/-14 / 118+/-7 to 144+/-16 / 94+/-10 mm Hg ( P < .0001 ) versus 181+/-13 / 117+/-5 to 171+/-17 / 110+/-11 mm Hg in the enalapril group ( P = ns ) . The profound decrease in blood pressure achieved with nisoldipine CC was accompanied by a significant reduction in left ventricular [ LV ] mass index , observed after only 2 months of treatment ( from 146+/-40 to 129+/-35 g/m2 , P = .05 ) . In contrast , enalapril had no effect on LV mass ( from 139+/-36 to 142+/-50 g/m2 , P = NS ) . The antihypertensive effect of nisoldipine CC was further demonstrated in the open phase , during which 24-h BP decreased from 180+/-14 / 118+/-6 mm Hg ( at baseline ) to 142+/-16 / 92+/-10 mm Hg at the end of the 16-week open phase ( P < .0001 ) . This effect was sustained with trough-to-peak ratio of 74 % for systolic and 67 % for diastolic BP , with further regression in LV mass . Reduction in 24-h systolic BP to < 135 mm Hg was associated with a greater degree of regression of LV mass index in patients treated with nisoldipine CC . The incidence of adverse events in both groups was low and both nisoldipine CC and enalapril were well tolerated . The incidence of significant ventricular arrhythmia was also low and did not change with treatment . In conclusion , our findings suggest that nisoldipine CC administered once daily could be considered as a suitable first-line antihypertensive agent in black patients with severe hypertension , based on its profound and sustained blood-pressure-lowering effect , associated with significant regression of left ventricular mass and its low side effect profile To determine whether a dose of 5 mg of nifedipine would be useful in the treatment of hypertensive emergencies , we compared the acute hypotensive effects of two different doses of nifedipine , 5 mg and 10 mg , in patients with severe hypertension . In this prospect i ve , r and omized , double-blind study , 30 consecutive black patients with diastolic blood pressure that was equal to or greater than 115 mm Hg received either a 5 mg or 10 mg nifedipine capsule and a placebo capsule , which matched that of the alternative strength . Patients were asked to bite the capsules and swallow the contents . Blood pressure response over 4 hours and adverse effects were monitored . Mean systolic blood pressure was reduced from 191.7 mm Hg ( 95 % confidence interval 170.8 to 212.7 mm Hg ) to 157.9 mm Hg ( 137.0 to 178.9 mm Hg ) and 206.1 mm Hg ( 185.1 to 227.0 mm Hg ) to 153.7 mm Hg ( 132.8 to 174.7 mm Hg ) in patients who were given 5 mg and 10 mg doses of nifedipine , respectively . Mean diastolic blood pressure in the group of patients that received 5 mg doses of nifedipine decreased from 128.2 mm Hg ( 115.6 to 140.7 mm Hg ) to 105.2 mm Hg ( 92.7 to 117.7 mm Hg ) ; the corresponding values in the group that received 10 mg doses of nifedipine were 129.9 mm Hg ( 117.4 to 142.5 mm Hg ) and 97.5 mm Hg ( 85.0 to 110.1 mm Hg ) , respectively . The minimum mean systolic blood pressures occurred 20 and 25 minutes after administration of the 5 mg and 10 mg capsules , respectively ; the minimum diastolic blood pressures were reached after 20 and 30 minutes , respectively . ( ABSTRACT TRUNCATED AT 250 WORDS Although clinical trials of the efficacy of antihypertensive treatment have demonstrated impressive reductions in the incidence of stroke , the reduction in coronary artery disease mortality has been less impressive . It may be that the antihypertensive drugs used in these trials induced metabolic disturbances , or produced inadequate regression of left ventricular hypertrophy , thus blunting the reduction in risk of coronary artery disease expected with blood pressure-lowering . Isradipine , a dihydropyridine calcium antagonist known to be an effective antihypertensive agent , has also displayed pronounced antiatherogenic effects in animals . Thus , a reasonable hypothesis could be that isradipine not only reduces the level of blood pressure , but also may have a positive effect on the evolution of atherosclerotic plaque in coronary and carotid arteries , thereby leading to prevention of clinical sequelae of atherosclerosis . On this basis , a 3-year clinical trial is being carried out in the United States – the Multicenter Isradipine/Diuretic Atherosclerosis Study (MIDAS)–to establish the efficacy of isradipine in inhibiting atherogenesis and retarding the progression of atherosclerosis in carotid arteries of hypertensive patients . The primary end point of the study is intima-media thickness and the extent of atherosclerotic plaque in the carotid arteries , as measured by B-mode ultrasonography BACKGROUND Despite treatment , there is often a higher incidence of cardiovascular complications in patients with hypertension than in normotensive individuals . Inadequate reduction of their blood pressure is a likely cause , but the optimum target blood pressure is not known . The impact of acetylsalicylic acid ( aspirin ) has never been investigated in patients with hypertension . We aim ed to assess the optimum target diastolic blood pressure and the potential benefit of a low dose of acetylsalicylic acid in the treatment of hypertension . METHODS 18790 patients , from 26 countries , aged 50 - 80 years ( mean 61.5 years ) with hypertension and diastolic blood pressure between 100 mm Hg and 115 mm Hg ( mean 105 mm Hg ) were r and omly assigned a target diastolic blood pressure . 6264 patients were allocated to the target pressure < or = 90 mm Hg , 6264 to < or = 85 mm Hg , and 6262 to < or = 80 mm Hg . Felodipine was given as baseline therapy with the addition of other agents , according to a five-step regimen . In addition , 9399 patients were r and omly assigned 75 mg/day acetylsalicylic acid ( Bamycor , Astra ) and 9391 patients were assigned  placebo . FINDINGS Diastolic blood pressure was reduced by 20.3 mm Hg , 22.3 mm Hg , and 24.3 mm Hg , in the < or = 90 mm Hg , < or = 85 mm Hg , and < or = 80 mm Hg target groups , respectively . The lowest incidence of major cardiovascular events occurred at a mean achieved diastolic blood pressure of 82.6 mm Hg ; the lowest risk of cardiovascular mortality occurred at 86.5 mm Hg . Further reduction below these blood pressures was safe .  In patients with diabetes mellitus there was a 51 % reduction in major cardiovascular events in target group < or = 80 mm Hg compared with target group < or = 90 mm Hg ( p for trend=0.005 ) . Acetylsalicylic acid reduced major cardiovascular events by 15 % ( p=0.03 ) and all myocardial infa rct ion by 36 % ( p=0.002 ) , with no effect on stroke . There were seven fatal bleeds in the acetylsalicylic acid group and eight in the placebo group , and 129 versus 70 non-fatal major bleeds in the two groups , respectively ( p<0.001 ) . INTERPRETATION Intensive lowering of blood pressure in patients with hypertension was associated with a low rate of cardiovascular events . The HOT Study shows the benefits of lowering the diastolic blood pressure down to 82.6 mm Hg . Acetylsalicylic acid significantly reduced major cardiovascular events with the greatest benefit seen in all myocardial infa rct ion . There was no effect on the incidence of stroke or fatal bleeds , but non-fatal major bleeds were twice as common OBJECTIVE The primary objective of the ABCD ( Appropriate Blood Pressure Control in Diabetes ) Trial is to determine the efficacy of intensive versus moderate antihypertensive control on the outcome of type II diabetic end-organ complications in normotensive and hypertensive population s. The secondary objective is to determine whether any differential effect on end-organ complications exists between an angiotensin converting enzyme inhibitor ( enalapril ) and a calcium channel blocker ( nisoldipine ) . DESIGN The ABCD Trial is a prospect i ve , controlled , r and omized , double-blind trial , with a planned follow-up of 5 years . SETTING All patients are seen at the Colorado Prevention Center , site of the ABCD Trial , for follow-up visits . PATIENTS Patients are type II diabetic males and females between the ages of 40 and 74 years with entry diastolic blood pressures > or = 80 mmHg . Patients were recruited from University of Colorado-affiliated hospitals , several health maintenance organizations , and mailing lists from the Colorado affiliate of the American Diabetes Association . INTERVENTIONS Patients were r and omized to intensive antihypertensive drug therapy or moderate antihypertensive drug therapy . Patients were also r and omized to nisoldipine or enalapril , with open-label medications added if further blood pressure control was necessary . MAIN OUTCOME MEASURES The primary outcome measure is glomerular filtration rate as assessed by 24-hour creatinine clearance . Secondary outcome measures are microalbumin urinary excretion , left ventricular hypertrophy , retinopathy , and neuropathy . Cardiovascular morbidity and mortality will also be evaluated . CONCLUSION Given the data showing the impact of hypertension on diabetic complications , the ABCD Trial was design ed to determine if intensive antihypertensive therapy will be more efficacious than moderate antihypertensive therapy on the outcome of these complications . Results from the ABCD Trial are expected to lend interpretable and clinical ly relevant findings with regards to the treatment of hypertension in type II diabetes BACKGROUND The efficacy of antihypertensive drugs newer than diuretics and beta-blockers has not been established . We compared the effects of the calcium-channel blocker nifedipine once daily with the diuretic combination co-amilozide on cardiovascular mortality and morbidity in high-risk patients with hypertension . METHODS We did a prospect i ve , r and omised , double-blind trial in Europe and Israel in 6321 patients aged 55 - 80 years with hypertension ( blood pressure > or = 150/95 mm Hg , or > or = 160 mm Hg systolic ) . Patients had at least one additional cardiovascular risk factor . We r and omly assigned patients nifedipine 30 mg in a long-acting gastrointestinal-transport-system ( GITS ) formulation ( n=3157 ) , or co-amilozide ( hydrochlorothiazide 25 mg [ corrected ] plus amiloride 2.5 mg ; n=3164 ) . Dose titration was by dose doubling , and addition of atenolol 25 - 50 mg or enalapril 5 - 10 mg . The primary outcome was cardiovascular death , myocardial infa rct ion , heart failure , or stroke . Analysis was done by intention to treat . FINDINGS Primary outcomes occurred in 200 ( 6.3 % ) patients in the nifedipine group and in 182 ( 5.8 % ) in the co-amilozide group ( 18.2 vs 16.5 events per 1000 patient-years ; relative risk 1.10 [ 95 % CI 0.91 - 1.34 ] , p=0.35 ) . Overall mean blood pressure fell from 173/99 mm Hg ( SD 14/8 ) to 138/82 mm Hg ( 12/7 ) . There was an 8 % excess of withdrawals from the nifedipine group because of peripheral oedema ( 725 vs 518 , p<0.0001 ) , but serious adverse events were more frequent in the co-amilozide group ( 880 vs 796 , p=0.02 ) . Deaths were mainly non-vascular ( nifedipine 176 vs co-amilozide 172 ; p=0.81 ) . 80 % of the primary events occurred in patients receiving r and omised treatment ( 157 nifedipine , 147 co-amilozide , difference 0.33 % [ -0.7 to 1.4 ] ) . INTERPRETATION Nifedipine once daily and co-amilozide were equally effective in preventing overall cardiovascular or cerebrovascular complications . The choice of drug can be decided by tolerability and blood-pressure response rather than long-term safety or efficacy A novel design for intervention studies is presented , the so called PROBE study ( Prospect i ve R and omized Open , Blinded End-point ) . This design is compared to the classical double-blind design . Among the advantages of the PROBE design are lower cost and greater similarity to st and ard clinical practice , which should make the results more easily applicable in routine medical care . Since end-points are evaluated by a blinded end-point committee it is obvious that there should be no difference between the two types of trials in this regard BACKGROUND The apparent shortfall in prevention of coronary heart disease ( CHD ) noted in early hypertension trials has been attributed to disadvantages of the diuretics and beta blockers used . For a given reduction in blood pressure , some suggested that newer agents would confer advantages over diuretics and beta blockers . Our aim , therefore , was to compare the effect on non-fatal myocardial infa rct ion and fatal CHD of combinations of atenolol with a thiazide versus amlodipine with perindopril . METHODS We did a multicentre , prospect i ve , r and omised controlled trial in 19 257 patients with hypertension who were aged 40 - 79 years and had at least three other cardiovascular risk factors . Patients were assigned either amlodipine 5 - 10 mg adding perindopril 4 - 8 mg as required ( amlodipine-based regimen ; n=9639 ) or atenolol 50 - 100 mg adding bendroflumethiazide 1.25 - 2.5 mg and potassium as required ( atenolol-based regimen ; n=9618 ) . Our primary endpoint was non-fatal myocardial infa rct ion ( including silent myocardial infa rct ion ) and fatal CHD . Analysis was by intention to treat . FINDINGS The study was stopped prematurely after 5.5 years ' median follow-up and accumulated in total 106 153 patient-years of observation . Though not significant , compared with the atenolol-based regimen , fewer individuals on the amlodipine-based regimen had a primary endpoint ( 429 vs 474 ; unadjusted HR 0.90 , 95 % CI 0.79 - 1.02 , p=0.1052 ) , fatal and non-fatal stroke ( 327 vs 422 ; 0.77 , 0.66 - 0.89 , p=0.0003 ) , total cardiovascular events and procedures ( 1362 vs 1602 ; 0.84 , 0.78 - 0.90 , p<0.0001 ) , and all-cause mortality ( 738 vs 820 ; 0.89 , 0.81 - 0.99 , p=0.025 ) . The incidence of developing diabetes was less on the amlodipine-based regimen ( 567 vs 799 ; 0.70 , 0.63 - 0.78 , p<0.0001 ) . INTERPRETATION The amlodipine-based regimen prevented more major cardiovascular events and induced less diabetes than the atenolol-based regimen . On the basis of previous trial evidence , these effects might not be entirely explained by better control of blood pressure , and this issue is addressed in the accompanying article . Nevertheless , the results have implication s with respect to optimum combinations of antihypertensive agents BACKGROUND Diabetic nephropathy is the most common cause of end-stage renal disease in the developed world . Angiotensin-converting enzyme inhibitors have been demonstrated to be renoprotective in type I diabetes and are now the st and ard of care for both hypertensive and non-hypertensive type I diabetic patients with any level of proteinuria . The role of blockade of the renin-angiotensin system in type II diabetic patients is not defined . The Collaborative Study Group has initiated the Irbesartan Type II Diabetic Nephropathy Trial ( IDNT ) , study ing the effect of the angiotensin II receptor antagonist irbesartan on progression of renal disease and mortality in type II diabetic patients with overt nephropathy and hypertension . Here we report the study design and baseline patient characteristics . METHODS To qualify , hypertensive type II patients , age 30 - 70 years , must have a 24 h urinary protein excretion of > 900 mg and a serum creatinine 90 - 265 micromol/l ( 1.0 - 3 . 0 mg/dl ) in women and 110 - 265 micromol/l ( 1.2 - 3.0 mg/dl ) in men . Three treatment arms include irbesartan , placebo and amlodipine , with every attempt made to achieve similar blood pressure levels in all treatment arms . A total of 1650 patients will be enrolled utilizing approximately 225 clinics worldwide . The primary outcome measure is time to event to the composite end-point of doubling of serum creatinine , end-stage renal disease or death . The secondary outcome measure is time to composite end-point of fatal or non-fatal cardiovascular events . The average length of patient follow-up is expected to be approximately 36 months . RESULTS The baseline characteristics of the study subjects are : age 59+/-8 years , duration of diabetes 15+/-9 years , height 168+/-11 cm ( 5 ft 6 in ) , weight 87+/-19 kg ( 192 lb ) , body mass index 31+/-7 kg/m(2 ) , blood pressure 156+/-18 mmHg/85+/-11 mmHg , serum creatinine 150+/-53 micromol/l ( 1.7+/-0.6 mg/dl ) , creatinine clearance 66+/-34 ml/min and 24 h urine protein 4.0+/-3.5 g/day The Controlled ONset Verapamil INvestigation of Cardiovascular Endpoints ( CONVINCE ) Trial is a r and omized , prospect i ve , double-blind , parallel-group , two-arm , actively controlled , multicenter , international 5-year clinical trial involving 15,000 patients . CONVINCE will compare the incidence of fatal or nonfatal myocardial infa rct ion ( MI ) , fatal or nonfatal stroke , or cardiovascular-disease-related death in two antihypertensive treatment regimens . One treatment arm begins with controlled onset-extended release (COER)-verapamil , which has its major antihypertensive effect 6 - 12 hours after administration . The other arm ( st and ard of care ( SOC ) ) begins with either hydrochlorothiazide ( HCTZ ) or atenolol , one of which is preselected by the investigator for an individual patient prior to r and omization . Secondary objectives include comparisons of the regimens for each of the components of the primary endpoint ( separately ) , death or hospitalization related to cardiovascular disease , efficacy in lowering blood pressure to goal , primary events occurring between 6 am and noon , all-cause mortality , withdrawals from blinded therapy , cancer , and hospitalizations due to bleeding .  Patients may be enrolled if they are hypertensive and at least 55 years of age and have an established second risk factor for cardiovascular disease . Initial medications include COER-verapamil ( 180 mg/d ) , HCTZ ( 12.5 mg/d ) , or atenolol ( 50 mg/d ) . Initial doses are doubled if blood pressure ( BP ) does not reach goal ( systolic BP < 140 mm and diastolic BP < 90 mm Hg ) . If BP is not controlled by the higher dose of the initial medication , HCTZ is added to COER-verapamil , or the SOC choice not initially selected is added in the SOC arm . An ACE-inhibitor is recommended ( although nearly any open-label medication is allowed ) as the third step for patients whose BP is not adequately controlled or who have a contraindication to one of the two SOC medications . Patients take two sets of tablets daily , one in the morning and one in the evening . Although most patients switch from an established antihypertensive medication to r and omized treatment , untreated patients with stages I-III hypertension ( SBP between 140 and 190 or DBP between 90 and 110 mm Hg ) are eligible . Outcomes are monitored by an independent Data and Safety Monitoring Board . Enrollment began during the third quarter of 1996 , and follow-up is to be completed in the third quarter of 2002 CONTEXT Antihypertensive therapy is well established to reduce hypertension-related morbidity and mortality , but the optimal first-step therapy is unknown . OBJECTIVE To determine whether treatment with a calcium channel blocker or an angiotensin-converting enzyme inhibitor lowers the incidence of coronary heart disease ( CHD ) or other cardiovascular disease ( CVD ) events vs treatment with a diuretic . DESIGN The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial ( ALLHAT ) , a r and omized , double-blind , active-controlled clinical trial conducted from February 1994 through March 2002 . SETTING AND PARTICIPANTS A total of 33 357 participants aged 55 years or older with hypertension and at least 1 other CHD risk factor from 623 North American centers . INTERVENTIONS Participants were r and omly assigned to receive chlorthalidone , 12.5 to 25 mg/d ( n = 15 255 ) ; amlodipine , 2.5 to 10 mg/d ( n = 9048 ) ; or lisinopril , 10 to 40 mg/d ( n = 9054 ) for planned follow-up of approximately 4 to 8 years . MAIN OUTCOME MEASURES The primary outcome was combined fatal CHD or nonfatal myocardial infa rct ion , analyzed by intent-to-treat . Secondary outcomes were all-cause mortality , stroke , combined CHD ( primary outcome , coronary revascularization , or angina with hospitalization ) , and combined CVD ( combined CHD , stroke , treated angina without hospitalization , heart failure [ HF ] , and peripheral arterial disease ) . RESULTS Mean follow-up was 4.9 years . The primary outcome occurred in 2956 participants , with no difference between treatments . Compared with chlorthalidone ( 6-year rate , 11.5 % ) , the relative risks ( RRs ) were 0.98 ( 95 % CI , 0.90 - 1.07 ) for amlodipine ( 6-year rate , 11.3 % ) and 0.99 ( 95 % CI , 0.91 - 1.08 ) for lisinopril ( 6-year rate , 11.4 % ) . Likewise , all-cause mortality did not differ between groups . Five-year systolic blood pressures were significantly higher in the amlodipine ( 0.8 mm Hg , P = .03 ) and lisinopril ( 2 mm Hg , P<.001 ) groups compared with chlorthalidone , and 5-year diastolic blood pressure was significantly lower with amlodipine ( 0.8 mm Hg , P<.001 ) . For amlodipine vs chlorthalidone , secondary outcomes were similar except for a higher 6-year rate of HF with amlodipine ( 10.2 % vs 7.7 % ; RR , 1.38 ; 95 % CI , 1.25 - 1.52 ) . For lisinopril vs chlorthalidone , lisinopril had higher 6-year rates of combined CVD ( 33.3 % vs 30.9 % ; RR , 1.10 ; 95 % CI , 1.05 - 1.16 ) ; stroke ( 6.3 % vs 5.6 % ; RR , 1.15 ; 95 % CI , 1.02 - 1.30 ) ; and HF ( 8.7 % vs 7.7 % ; RR , 1.19 ; 95 % CI , 1.07 - 1.31 ) . CONCLUSION Thiazide-type diuretics are superior in preventing 1 or more major forms of CVD and are less expensive . They should be preferred for first-step antihypertensive therapy Treatment of hypertension with ACE inhibitors in diabetic patients reduces proteinuria and slows progression of nephropathy compared with agents that do not maintain declines in proteinuria . Calcium channel blockers ( CCBs ) have variable effects on proteinuria ; their long-term effects on progression of diabetic nephropathy are not known . The current study examines the hypothesis that CCBs that maintain reductions in proteinuria slow progression of nephropathy associated with non-insulin dependent diabetes mellitus ( NIDDM ) by a degree comparable to ACE inhibitors , given similar levels of blood pressure control . To test this hypothesis we r and omized 52 patients with NIDDM associated nephropathy and hypertension , mean age of 63 + /- 8 years , to either the ACE inhibitor , lisinopril ( N = 18 ) , nondihydropyridine CCBs ( NDCCBs ) , verapamil SR ( N = 8) or diltiazem SR ( N = 10 ) , or the beta blocker , atenolol ( N = 16 ) . Goal blood pressure was < or = 140/90 mm Hg . Patients were followed for a mean period of 63 + /- 7 months . The primary end point was change in creatinine clearance ( CCr ) slope in each group . There was no significant difference in mean arterial pressure reduction among the groups over the study period ( P = 0.14 ) . The mean rate of decline in CCr was greatest in the atenolol group ( -3.48 ml/min/year/1.73 m2 ; P < 0.0001 ) . There was no difference in the CCr slopes between lisinopril and NDCCBs groups ( P = 0.36 ) . Proteinuria was reduced to a similar extent in the lisinopril and NDCCBs groups ( P > 0.99 ) . Therefore , in persons with renal insufficiency secondary to NIDDM , similar levels of blood pressure control with either lisinopril or NDCCBs slowed progression of renal disease to a greater extent than atenolol . Moreover , this enhanced slowing of renal disease progression correlated with sustained and significant reductions in proteinuria , findings not observed in the atenolol group OBJECTIVE To assess the association between  first myocardial infa rct ion and the use of antihypertensive agents .  DESIGN AND SETTING We conducted a population -based case-control study among enrollees of the Group Health Cooperative of Puget Sound ( GHC ) . PATIENTS AND METHODS Cases were hypertensive patients who sustained a first fatal or nonfatal myocardial infa rct ion from 1986 through 1993 among women and from 1989 through 1993 among men . Controls were a stratified r and om sample of hypertensive GHC enrollees , frequency matched to the cases on age , sex , and calendar year . All 623 cases and 2032 controls had pharmacologically treated hypertension . Data collection included a review of the ambulatory medical record a brief telephone interview of consenting survivors . Antihypertensive therapy was assessed using the GHC 's computerized pharmacy data base . RESULTS The first analysis included only the 335 cases and 1395 controls initially free of cardiovascular disease . Compared with users of diuretics alone , the adjusted risk ratio of myocardial infa rct ion was increased by about 60 % among users of calcium channel blockers with or without diuretic ( risk ratio = 1.62 % ; 95 % confidence interval [ Cl ] , 1.11 to 2.34 ; P = .01 ) . The second analysis was restricted to 384 cases and 1108 controls who were taking either a calcium channel blocker or a beta-blocker .  Among these subjects , the use of calcium channel blockers compared with beta-blockers was associated with about a 60 % increase in the adjusted risk of myocardial infa rct ion ( risk ratio = 1.57 ; 95 % Cl , 1.21 to 2.04 ; P < .001 ) . While high doses of beta-blockers were associated with a decreased risk of myocardial infa rct ion ( trend P = .04 ) , high doses of calcium channel blockers were associated with an increased risk ( trend P < .01 ) . CONCLUSIONS In this study of hypertensive patients , the use of short-acting calcium channel blockers , especially in high doses , was associated with an increased risk of myocardial infa rct ion . Ongoing large-scale clinical trials will assess the effect of various antihypertensive therapies , including calcium channel blockers , on several important cardiovascular end points . Until these results are available , the findings of this study support the current guidelines from the Joint National Committee on the Detection , Evaluation and Treatment of High Blood Pressure that recommend diuretics and beta-blockers as first-line agents unless contraindicated , unacceptable , or not tolerated Objective To test the primary hypothesis that a newer antihypertensive treatment regimen ( calcium channel blocker ± an angiotensin converting enzyme inhibitor ) is more effective than an older regimen ( β-blocker ± a diuretic ) in the primary prevention of coronary heart disease ( CHD ) . To test a second primary hypothesis that a statin compared with placebo will further protect against CHD endpoints in hypertensive subjects with a total cholesterol ⩽ 6.5 mmol/l . Design Prospect i ve , r and omized , open , blinded endpoint trial with a double-blinded 2 × 2 factorial component . Setting Patients were recruited mainly from general practice s. Patients Men and women aged 40–79 were eligible if their blood pressure was ⩾160 mmHg systolic or ⩾ 100 mmHg diastolic ( untreated ) or ⩾140 mmHg systolic or ⩾ 90 mmHg diastolic ( treated ) at r and omization . Interventions Patients received either amlodipine ( 5/10 mg ) ± perindopril ( 4/8 mg ) or atenolol ( 50/100 mg ) ± bendroflumethiazide ( 1.25/2.5 mg ) + K+ with further therapy as required to reach a blood pressure of ⩽140 mmHg systolic and 90 mmHg diastolic . Patients with a total cholesterol of ⩽ 6.5 mmol/l were further r and omized to receive either atorvastatin 10 mg or placebo daily . Main outcome measure Non-fatal myocardial infa rct ion ( MI ) and fatal coronary heart disease ( CHD ) . Results 19 342 men and women were initially r and omized , of these 10 297 were also r and omized into the lipid-lowering limb . All patients had three or more additional cardiovascular risk factors . Conclusions The study has 80 % power ( at the 5 % level ) to detect a relative difference of 20 % in CHD endpoints between the calcium channel blocker-based regimen and the β-blocker-based regimen . The lipid-lowering limb of the study has 90 % power at the 1 % level to detect a relative difference of 30 % in CHD endpoints between groups PREVALENCE OF  HYPERTENSION IN ELDERLY JAPANESE PATIENTS : Data collected from post-mortem information at the Tokyo Metropolitan Geriatric Hospital showed that the overall prevalence of hypertension in Japanese patients aged over 60 years was 53 % ; one-third of these elderly hypertensives had isolated systolic hypertension . Isolated systolic and systolodiastolic hypertension were each associated with a similar degree of increased atherosclerosis and cardiovascular complications . In a placebo-controlled study antihypertensive treatment produced a reduction in withdrawal from treatment in elderly patients with mild hypertension . INTERIM TRIAL RESULTS : Some interim results have been obtained from a new trial which is currently under way in Japan , the National Intervention Cooperative Study for the Treatment of Elderly Hypertensives , a long-term study comparing the effects of a calcium antagonist ( nicardipine ) and a thiazide diuretic ( trichlormethiazide ) on cardiovascular complications in elderly patients with mild to moderate hypertension Blood pressure ( BP ) control rates around the world are suboptimal . Part 2 of the National Health and Nutrition Educational Survey ( NHANES ) III indicates that only 27.4 % of hypertensive Americans aged 18 to 74 years have a BP of < 140/90 mm Hg . We wanted to assess BP control during the first 2 years and to describe the baseline characteristics of patients enrolled in the Controlled ONset Verapamil INvestigation of Cardiovascular Endpoints ( CONVINCE ) Study , an international clinical trial that compares outcomes in hypertensive patients r and omized to initial treatment with either controlled-onset extended-release verapamil  or the investigator ’s choice of atenolol or hydrochlorothiazide . At r and omization , BP was < 140/90 mm Hg in only 20.3 % of the 16 602 subjects ( average±SD age 65.6±7.4 years ; 56 % women , 84 % white/7 % black/7 % Hispanic ) . The  average BP  at enrollment was 148/85 mm Hg for patients taking BP medications ( n=13 879 ) and 161/94 mm Hg for previously untreated patients ( n=2723 ) . After medication titration , with a transtelephonic computer that recommended an increase in the dose or number of antihypertensive agents whenever the BP was 140/90 mm Hg , 84.8 % of the subjects attained the goal BP . During 2 years of treatment , BP control was maintained in 67 % to 69 % of the subjects ( 69 % to 71 % for systolic BP of < 140 mm Hg and 90 % for diastolic BP of < 90 mm Hg ) . These data suggest that the control of systolic BP is more difficult than the control of diastolic BP . The US national goal of having 50 % of hypertensives with a BP of < 140/90 mm Hg may be achievable if a forced titration strategy is used . Interested investigators , free care and medications , and well-educated subjects may make the attainment of such a goal easier in the CONVINCE study than in the general population Background It is unclear whether the carotid intima – media thickness can be influenced by antihypertensive treatment and whether some antihypertensive agents , such as calcium antagonists , may have a greater effect on this parameter than others , such as diuretics . The present paper reports the principal results of the ultrasound sub study of the r and omized , prospect i ve , controlled , Verapamil in Hypertension and Atherosclerosis Study ( VHAS ) . Design and methods In 498 hypertensive patients in eight Italian centres , r and omized to either verapamil ( 240 mg once a day ) or chlorthalidone ( 25 mg once a day ) , a B-mode ultrasound scan was performed according to a st and ardized procedure at baseline and after 3 , 12 , 24 , 36 and 48 months of treatment . The maximum intima – media thicknesses of the far walls of common , bifurcation and internal carotid arteries were measured bilaterally , and the following indices calculated : the mean thickness at the six measured sites , the mean thickness at the common and bifurcation sites and the single maximum thickness . The primary endpoint for treatment efficacy was the slope of the change over 4 years ( rate of change , mm/year ) , corrected by using the initial mean over the six sites ( baseline + 3 months ) as a covariate ( mm/year per mm ) . The patients were also classified into three strata according to their baseline single maximum thickness : those with normal carotid arteries ( single maximum ( 1 mm ) , those with thickened carotid arteries ( single maximum > 1 and ≤ 1.5 mm and those with carotid plaques ( single maximum > 1.5 mm ) . Results Among the 456 patients with satisfactory baseline ultrasound readings , 33 % were classified with normal carotid arteries , 27 % with thickened carotid arteries and 40 % with plaques . In the intention-to-treat population ( 377 patients with ultrasound measurements taken on at least three different occasions over a period of at least 2 years ) , the rate of change in the mean thickness at the six sites measured was rather small ( 0.015 mm/year ) , but significantly ( P < 0.05 ) smaller in patients with plaques ( 0.003 mm/year ) than in patients with thickened or with normal carotids ( 0.023 and 0.025 mm/year , respectively ) . When related to initial values , the rate of change in the mean thickness at the six sites had a negative slope ( −0.059 mm/year per mm , P < 0.01 ) . Although rates of change in the carotid intima – media thickness in unstratified patients were not different in those treated with verapamil or with chlorthalidone , when changes in the mean thickness of six sites were related to the initial value , the slope of this relationship was significantly different in the two treatment groups ( verapamil −0.082 versus chlorthalidone −0.037 mm/year per mm , P < 0.02 ) . The blood pressure-lowering effect of the two r and omized treatments was similar . Taking fatal and nonfatal , major and minor cardiovascular events together , there were 19 events in the verapamil group and 35 in the chlorthalidone group , with a significantly ( P < 0.01 ) greater incidence in patients with plaques , and among patients with plaques in those who were r and omized to chlorthalidone ( P < 0.05 ) . Conclusions In accord with evidence from animal models of atherosclerosis , the calcium antagonist verapamil was more effective than the diuretic chlorthalidone in promoting regression of thicker carotid lesions . Changes in the carotid intima – media thickness were small in both groups , and the differences between the changes under the two treatments were consequently small , but the observation that these small differences in carotid wall changes were paralleled by differences in the incidence of cardiovascular events ( better intima – media thickness regression with verapamil paralleled by a lower cardiovascular event rate ) suggests that even small effects on carotid plaques may have clinical and prognostic relevance OBJECTIVE The Swedish Trial in Old Patients with Hypertension-2 ( STOP-Hypertension-2 ) was design ed by a project group of the Swedish Hypertension Society to test whether the " newer " treatment alternatives ( ACE inhibitors and calcium antagonists ) are as good as , better or less good than , the " older " ones ( beta-blockers and diuretics ) in terms of preventing cardiovascular morbidity and mortality  in elderly hypertensives . The aim of the present paper is to report on the progress of the study . DESIGN Prospect i ve , open trial with blinded end-point committee and central ized r and omization ( PROBE design ) . STOP-Hypertension-2 may be regarded as a scientific follow-up of the previously published Swedish Trial in Old Patients with Hypertension ( STOP-Hypertensioon-1 ) ( 6 ) using the same study organization . SUBJECTS By the end of 1994 when recruitment was stopped , 6628 hypertensive men ( 34 % ) and women ( 66 % ) aged 70 - 84 ( mean age 76 ) had been included at 312 Swedish health centres ( out of approximately 850 ) . In the whole cohort 11 % are diabetics and 9 % smokers . The mean total cholesterol value is 6.5 mmol/L. RESULTS In the whole study cohort , blood pressure was lowered from 194/98 mmHg to 167/85 mmHg after one year . At the end of 1995 , 319 fatal events ( all-cause mortality ) had been reported , corresponding to a mortality rate of 21.3 per 1000 person-years . CONCLUSION In STOP-Hypertension-2 , 6628 elderly hypertensive have been r and omized to three different treatment regimes : beta-blocker+diuretics ( the active treatment arm in STOP-Hypertension-1 ) , ACE inhibitors , or calcium antagonists . Their average lowering of blood pressure was 27/13 mmHg and end-points have occurred at the expected rate . Thus , it should be possible to terminate STOP-Hypertension-2 within two to three years BACKGROUND Patients with chronic kidney disease are at increased risk for cardiovascular ( CV ) events . METHODS We r and omly assigned 1,094 African Americans with hypertensive nephrosclerosis ( glomerular filtration rate [ GFR ] , 20 to 65 mL/min/1.73 m(2 ) [ 0.33 to 1.08 mL/s ] ) to initial antihypertensive treatment with either : ( 1 ) a beta-blocker , metoprolol ; ( 2 ) an angiotensin-converting enzyme inhibitor , ramipril ; or ( 3 ) a dihydropyridine calcium channel blocker , amlodipine , and either a usual-blood pressure ( BP ) or low-BP treatment goal . Using a design powered to detect renal outcome differences , we compared the effect of treatment on the CV event rate ( cardiac death , myocardial infa rct ion , stroke , and heart failure ) during a mean follow-up period of 4.1 years and determined baseline factors that predict CV outcomes . RESULTS Thirty-one patients died of CV disease ( 0.7%/patient-year ) , and 149 patients experienced at least 1 CV outcome ( 3.3%/patient-year ) . Overall , 202 CV events ( 4.5%/patient-year ) occurred . The CV outcome rate was not related significantly to r and omized interventions . In multivariable analyses , 7 baseline risk factors remained independently associated with increased risk for the CV composite outcome after controlling for age , sex , baseline GFR , and baseline proteinuria group : pulse pressure , duration of hypertension , abnormal electrocardiogram result , non-high-density lipoprotein cholesterol level , serum urea nitrogen level , urine protein-creatinine ratio , urine sodium-potassium ratio , and annual income less than 15,000 dollars . CONCLUSION Neither r and omized class of antihypertensive therapy nor BP level had a significant effect on the occurrence of CV events , possibly because of limited power . However , this analysis identifies unique and potentially modifiable CV risk factors in this high-risk cohort CONTEXT Studies have demonstrated that statins administered to individuals with risk factors for coronary heart disease ( CHD ) reduce CHD events . However , many of these studies were too small to assess all-cause mortality or outcomes in important subgroups . OBJECTIVE To determine whether pravastatin compared with usual care reduces all-cause mortality in older , moderately hypercholesterolemic , hypertensive participants with at least 1 additional CHD risk factor . DESIGN AND SETTING Multicenter ( 513 primarily community-based North American clinical centers ) , r and omized , nonblinded trial conducted from 1994 through March 2002 in a subset of participants from the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial ( ALLHAT ) . PARTICIPANTS Ambulatory persons ( n = 10 355 ) , aged 55 years or older , with low-density lipoprotein cholesterol ( LDL-C ) of 120 to 189 mg/dL ( 100 to 129 mg/dL if known CHD ) and triglycerides lower than 350 mg/dL , were r and omized to  pravastatin  ( n = 5170 ) or to  usual care  ( n = 5185 ) . Baseline mean total cholesterol was 224 mg/dL ; LDL-C , 146 mg/dL ; high-density lipoprotein cholesterol , 48 mg/dL ; and triglycerides , 152 mg/dL. Mean age was 66 years , 49 % were women , 38 % black and 23 % Hispanic , 14 % had a history of CHD , and 35 % had type 2 diabetes . INTERVENTION Pravastatin , 40 mg/d , vs usual care . MAIN OUTCOME MEASURES The primary outcome was all-cause mortality , with follow-up for up to 8 years . Secondary outcomes included nonfatal myocardial infa rct ion or fatal CHD ( CHD events ) combined , cause-specific mortality , and cancer . RESULTS Mean follow-up was 4.8 years . During the trial , 32 % of usual care participants with and 29 % without CHD started taking lipid-lowering drugs . At year 4 , total cholesterol levels were reduced by 17 % with pravastatin vs 8 % with usual care ; among the r and om sample who had LDL-C levels assessed , levels were reduced by 28 % with pravastatin vs 11 % with usual care .  All-cause mortality was similar for the 2 groups ( relative risk [ RR ] , 0.99 ; 95 % confidence interval [ CI ] , 0.89 - 1.11 ; P = .88 ) , with 6-year mortality rates of 14.9 % for pravastatin vs 15.3 % with usual care .  CHD event rates were not significantly different between the groups ( RR , 0.91 ; 95 % CI , 0.79 - 1.04 ; P = .16 ) , with 6-year CHD event rates of 9.3 % for pravastatin and 10.4 % for usual care . CONCLUSIONS Pravastatin did not reduce either all-cause mortality or CHD significantly when compared with usual care in older participants with well-controlled hypertension and moderately elevated LDL-C. The results may be due to the modest differential in total cholesterol ( 9.6 % ) and LDL-C ( 16.7 % ) between pravastatin and usual care compared with prior statin trials supporting cardiovascular disease prevention OBJECTIVE To determine whether older persons with hypertension who use specific calcium antagonists and ACE inhibitors  have a different risk of mortality than those using beta-blockers . DESIGN A prospect i ve cohort study continuing from 1988 through 1992 . SETTING Three communities of the Established Population s for Epidemiologic Studies of the Elderly . PARTICIPANTS Hypertensive participants aged > or = 71 years ( n = 906 ) who had no evidence of congestive heart failure and who were using either beta-blockers ( n = 515 ) , verapamil ( n = 77 ) , diltiazem ( n = 92 ) , nifedipine ( n = 74 ) , or ACE inhibitors ( n = 148 ) .  Nifedipine was of the short acting variety . MEASUREMENTS The main outcome measure was all-cause mortality . Age , gender , smoking , HDL-cholesterol , blood pressure , intake of digoxin and diuretics , physical disability , self-perceived health , and comorbid conditions were examined as confounders . RESULTS During 3538 person-years of follow-up , 188 participants died ( 53 deaths per 1000 person-years ) . Compared with beta-blockers , after adjusting for age , gender , comorbid conditions and other health-related factors , the relative risks ( 95 % confidence interval ) for mortality associated with use of verapamil , diltiazem , nifedipine , and ACE inhibitors were 0.8 ( 0.4 - 1.4 ) , 1.3 ( 0.8 - 2.1 ) , 1.7 ( 1.1 - 2.7 ) , and 0.9 ( 0.6 - 1.4 ) , respectively . The results were unchanged after excluding participants with other potential contraindications to beta-blockers and after stratifying on coronary heart disease and use of diuretics . Higher doses of nifedipine were associated with higher mortality . CONCLUSION Compared with beta-blockers , use of short acting nifedipine was associated with decreased survival in older hypertensive persons . However , selective factors influencing the use of specific drugs in higher risk patients could not be completely discounted , and final conclusions will depend on clinical trials OBJECTIVE To compare the rate of progression of mean maximum intimal-medial thickness ( IMT ) in carotid arteries , using quantitative B-mode ultrasound imaging , during  antihypertensive therapy with isradipine vs hydrochlorothiazide . DESIGN R and omized , double-blind , positive-controlled trial . SETTING Nine medical center clinics . POPULATION A total of 883 patients with baseline mean + /- SD systolic and diastolic blood pressure ( SBP and DBP , respectively ) of 149.7 + /- 16.6 and 96.5 + /- 5.1 mm Hg , age of 58.5 + /- 8.5 years , and maximum IMT of 1.17 + /- 0.20 mm . INTERVENTIONS Twice daily doses of isradipine ( 2.5 - 5.0 mg ) or hydrochlorothiazide ( 12.5 - 25 mg ) . MAIN OUTCOME MEASURE ( PRIMARY END POINT ) : Rate of progression of mean maximum IMT in 12 carotid focal points over 3 years . RESULTS There was no difference in the rate of progression of mean maximum IMT between isradipine and hydrochlorothiazide over 3 years ( P=.68 ) . There was a higher incidence of major vascular events ( eg , myocardial infa rct ion , stroke , congestive heart failure , angina , and sudden death ) in isradipine ( n=25 ; 5.65 % ) vs hydrochlorothiazide ( n=14 ; 3.17 % ) ( P=.07 ) , and a significant increase in nonmajor vascular events and procedures ( eg , transient ischemic attack , dysrhythmia , aortic valve replacement , and femoral popliteal bypass graft ) in isradipine ( n=40 ; 9.05 % ) vs hydrochlorothiazide ( n=23 ; 5.22 % ) ( P=.02 ) . At 6 months , mean DBP decreased by 13.0 mm Hg in both groups , and mean SBP decreased by 19.5 mm Hg in hydrochlorothiazide and 16.0 mm Hg in isradipine ( P=.002 ) ; the difference in SBP between the 2 groups persisted throughout the study but did not explain the increased incidence of vascular events in patients treated with isradipine . CONCLUSION The rate of progression of mean maximum IMT in carotid arteries , the surrogate end point in this study , did not differ between the 2 treatment groups . The increased incidence of vascular events in patients receiving isradipine compared with hydrochlorothiazide is of concern and should be studied further Background Isolated systolic hyprtension occurs in around 8 % of Chinese people aged 60 years or older . In 1988 , the Systolic Hypertension in China ( Syst-China ) Collaborative Group started to investigate whether active treatment could reduce the incidence of stroke and other cardiovascular complications in older patients with isolated systolic hypertension . Methods All patients were initially started on masked placebo . After stratification for centre , sex and previous cardiovascular complications , alternate patients ( n = 1253 ) were assigned nitrendipine at 10–40 mg daily , with the addition of captopril at 12.5–50.0 mg daily or hydrochlorothiazide at 12.5–50.0 mg daily , or both , if a sufficient blood pressure fall was not obtained . In the remaining 1141 control patients , matching placebos were administered similarly . Results At entry , sitting blood pressure averaged 170.5 mmHg systolic and 86.0 mmHg diastolic , age averaged 66.5 years and total serum cholesterol was 5.1 mmol/l . After 2 years of follow-up , sitting systolic and diastolic blood pressures had fallen by 10.9 mmHg and 1.9 mmHg in the placebo group and by 20.0 mmHg and 5.0 mmHg in the active treatment group . The intergroup differences were 9.1 mmHg systolic ( 95 % confidence interval 7.6–10.7 mmHg ) and 3.2 mmHg diastolic ( 95 % confidence interval 2.4–4.0 ) . Active treatment reduced total strokes by 38 % ( from 20.8 to 13.0 endpoints per 1000 patient-years , P = 0.01 ) , all-cause mortality by 39 % ( from 28.4 to 17.4 endpoints per 1000 patient-years , P = 0.003 ) , cardiovascular mortality by 39 % ( from 15.2 to 9.4 endpoints per 1000 patient-years , P = 0.03 ) , stroke mortality by 58 % ( from 6.9 to 2.9 endpoints per 1000 patient-years , P = 0.02 ) , and all fatal and nonfatal cardiovascular endpoints by 37 % ( from 33.3 to 21.4 endpoints per 1000 patient-years , P = 0.004 ) . Conclusions Antihypertensive treatment prevents stroke and other cardiovascular complications in older Chinese patients with isolated systolic hypertension . Treatment of 1000 Chinese patients for 5 years could prevent 55 deaths , 39 strokes or 59 major cardiovascular endpoints The Treatment of Mild Hypertension Study ( TOMHS ) is a r and omized , double-blind clinical trial currently being conducted to compare the effects of nonpharmacologic therapy alone with those of 1 of 5 active drug regimens combined with nonpharmacologic therapy , for long-term management of patients with mild hypertension . Six classes of drugs were studied : ( 1 ) acebutolol ( beta blocker ) , ( 2 ) amlodipine ( calcium antagonist ) , ( 3 ) chlorthalidone ( diuretic ) , ( 4 ) doxazosin ( alpha 1 antagonist ) , ( 5 ) enalapril ( angiotensin-converting enzyme inhibitor ) and ( 6 ) placebo . All participants received nutritional-hygienic advice to reduce weight and sodium and alcohol intakes and to increase physical activity . End points include blood pressure change , side effects and quality -of-life indices ; incidence of electrocardiographic and echocardiographic abnormalities ; and incidence of cardiovascular clinical events , including death , among participants receiving drugs as first-step treatment as well as nonpharmacologic treatment compared with incidence among those participants r and omized to nonpharmacologic treatment only as the initial step
target: Diuretics are preferred first-line over CCBs to optimize reduction of cardiovascular events .
  The review does not distinguish between CCBs , ACE inhibitors or ARBs , but does provide evidence supporting the use of CCBs over beta-blockers .
background: BACKGROUND Calcium channel blockers ( CCBs ) are a relatively new antihypertensive class .
  The effect of first-line CCBs on the prevention of cardiovascular events , as compared with other antihypertensive drug classes , is unknown .
  OBJECTIVES To determine whether CCBs used as first-line therapy for hypertension are different from other first-line drug classes in reducing the incidence of major adverse cardiovascular events .