title: A comparison of outcomes with angiotensin-converting--enzyme inhibitors and diuretics for hypertension in the elderly. Treatment of Hypertension in Patients 85 Years of Age or Older: A J-BRAVE Substudy Immediate and late benefits of treating very elderly people with hypertension: results from active treatment extension to Hypertension in the Very Elderly randomised controlled trial Results of the pilot study for the Hypertension in the Very Elderly Trial Combination therapy for hypertension in the elderly: a sub-analysis of the Combination Therapy of Hypertension to Prevent Cardiovascular Events (COPE) Trial Target Blood Pressure for Treatment of Isolated Systolic Hypertension in the Elderly: Valsartan in Elderly Isolated Systolic Hypertension Study Mortality and morbidity during and after the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial. Effect of Antihypertensive Treatment on Cardiovascular Events in Elderly Hypertensive Patients: Japan's Benidipine Research on Anti-Hypertensive Effects in the Elderly (J-BRAVE) Treatment of hypertension in patients 80 years of age or older. 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 Incident dementia and blood pressure lowering in the Hypertension in the Very Elderly Trial cognitive function assessment (HYVET-COG): a double-blind, placebo controlled trial Artist® Tablets (Carvedilol) for Hypertensive Patients in Japan Stroke prevention with the angiotensin II type 1-receptor blocker candesartan in elderly patients with isolated systolic hypertension: the Study on Cognition and Prognosis in the Elderly (SCOPE). The Study on Cognition and Prognosis in the Elderly (SCOPE): principal results of a randomized double-blind intervention trial Antihypertensive efficacy and side effects of three beta‐blockers and a diuretic in elderly hypertensives: a report from the STOP‐Hypertension study Cardiovascular events in elderly patients with isolated systolic hypertension. A subgroup analysis of treatment strategies in STOP‐Hypertension‐2 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). Principal Results of the Japanese Trial to Assess Optimal Systolic Blood Pressure in Elderly Hypertensive Patients (JATOS) Relation between drug treatment and cancer In hypertenslves in the Swedish Trial in Old Patients with Hypertension 2: a 5-year, prospective, randomised, controlled trial Comparison of antihypertensive treatments in preventing cardiovascular events in elderly diabetic patients: results from the Swedish Trial in Old Patients with Hypertension–2 The effect of treatment based on a diuretic (indapamide) +/- ACE inhibitor (perindopril) on fractures in the Hypertension in the Very Elderly Trial (HYVET). Medical Research Council trial of treatment of hypertension in older adults: principal results. MRC Working Party. The Hypertension Optimal Treatment (HOT) Study: 12-month data on blood pressure and tolerability. With special reference to age and gender. Angiotensin II receptor blocker-based therapy in Japanese elderly, high-risk, hypertensive patients. 2013 ESH/ESC guidelines for the management of arterial hypertension: the Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). 2014 evidence-based guideline for the management of high blood pressure in adults: report from the panel members appointed to the Eighth Joint National Committee (JNC 8).
abstract: BACKGROUND Treatment of hypertension with diuretics , beta-blockers , or both leads to improved outcomes . It has been postulated that agents that inhibit the renin-angiotensin system confer benefit beyond the reduction of blood pressure alone . We compared the outcomes in older subjects with hypertension who were treated with angiotensin-converting-enzyme ( ACE ) inhibitors with the outcomes in those treated with diuretic agents . METHODS We conducted a prospect i ve , r and omized , open-label study with blinded assessment of end points in 6083 subjects with hypertension who were 65 to 84 years of age and received health care at 1594 family practice s. Subjects were followed for a median of 4.1 years , and the total numbers of cardiovascular events in the two treatment groups were compared with the use of multivariate proportional-hazards models . RESULTS At base line , the treatment groups were well matched in terms of age , sex , and blood pressure . By the end of the study , blood pressure had decreased to a similar extent in both groups ( a decrease of 26/12 mm Hg ) . There were 695 cardiovascular events or deaths from any cause in the ACE-inhibitor group ( 56.1 per 1000 patient-years ) and 736 cardiovascular events or deaths from any cause in the diuretic group ( 59.8 per 1000 patient-years ; the hazard ratio for a cardiovascular event or death with ACE-inhibitor treatment was 0.89 [ 95 percent confidence interval , 0.79 to 1.00 ] ; P=0.05 ) . Among male subjects , the hazard ratio was 0.83 ( 95 percent confidence interval , 0.71 to 0.97 ; P=0.02 ) ; among female subjects , the hazard ratio was 1.00 ( 95 percent confidence interval , 0.83 to 1.21 ; P=0.98 ) ; the P value for the interaction between sex and treatment-group assignment was 0.15 . The rates of nonfatal cardiovascular events and myocardial infa rct ions decreased with ACE-inhibitor treatment , whereas a similar number of strokes occurred in each group ( although there were more fatal strokes in the ACE-inhibitor group ) . CONCLUSIONS Initiation of antihypertensive treatment involving ACE inhibitors in older subjects , particularly men , appears to lead to better outcomes than treatment with diuretic agents , despite similar reductions of blood pressure Whether the strict control of blood pressure ( BP ) of patients with hypertension who are aged 85 years or older is beneficial is unclear . The Japan ’s Benidipine Research on Antihypertensive Effects in the Elderly study is a prospect i ve , observational 3-year study to evaluate the safety and effectiveness of treatment with a calcium channel blocker benidipine in 8897 hypertensive patients aged 65 years or older as a post-marketing surveillance . We examined the relationship between the achieved BP and cardiovascular events ( i.e. , stroke , myocardial infa rct ion , and heart failure ) in a subgroup of 415 patients aged 85 years or older ( mean age 88 years ) . BP decreased significantly from 165 ± 14/84 ± 10 mmHg to 130 ± 11/71 ± 10 mmHg during treatment in patients with a treated systolic BP ( SBP ) < 140 mmHg ( n = 230 ) and BP decreased significantly from 169 ± 16/86 ± 12 mmHg to 143 ± 13/75 ± 10 mmHg in those with a treated SBP ≥ 140 mmHg ( n = 185 ) . There was a nonsignificant trend toward a lower rate of cardiovascular events and higher rate of total death in patients with a treated SBP < 140 mmHg . On-treatment SBP ≥ 160 mmHg is tended to associate with a higher incidence of cardiovascular events . There was no significant difference in the incidence of adverse reactions between the controlled BP group ( 3.04 % ) and the less well controlled BP group ( 3.24 % ) . In conclusion , although this study was not powered for definitive conclusion , there was a nonsignificant trend toward a lower rate of cardiovascular events and higher total death in patients aged 85 years or older with a treated SBP < 140 mmHg Objective To assess if very elderly people with hypertension obtain early benefit from antihypertensive treatment . Design One year open label active treatment extension of r and omised controlled trial ( Hypertension in the Very Elderly Trial ( HYVET ) ) . Setting Hospital and general practice based centres mainly in eastern and western Europe , China , and Tunisia . Participants People on double blind treatment at the end of HYVET were eligible to enter the extension . Interventions Participants on active blood pressure lowering treatment continued taking active drug ; those on placebo were given active blood pressure lowering treatment . The treatment regimen was as used in the main trial — indapamide SR 1.5 mg ( plus perindopril 2 - 4 mg if required)—with the same target blood pressure of less than 150/80 mm Hg . Main outcome measures The primary outcome was all stroke ; other outcomes included total mortality , cardiovascular mortality , and cardiovascular events . Results Of 1882 people eligible for entry to the extension , 1712 ( 91 % ) agreed to participate . During the extension period , 1682 patient years were accrued . By six months , the difference in blood pressure between the two groups was 1.2/0.7 mm Hg . Comparing people previously treated with active drug and those previously on placebo , no significant differences were seen for stroke ( n=13 ; hazard ratio 1.92 , 95 % confidence interval 0.59 to 6.22 ) or cardiovascular events ( n=25 ; 0.78 , 0.36 to 1.72 ) . Differences were seen for total mortality ( 47 deaths ; hazard ratio 0.48 , 0.26 to 0.87 ; P=0.02 ) and cardiovascular mortality ( 11 deaths ; 0.19 , 0.04 to 0.87 ; P=0.03 ) . Conclusion Very elderly patients with hypertension may gain immediate benefit from treatment . Sustained differences in reductions of total mortality and cardiovascular mortality reinforce the benefits and support the need for early and long term treatment . Trial registration Clinical trials NCT00122811 Background The risks and benefits of treating hypertension in individuals older than 80 years are uncertain . A meta- analysis has suggested that a reduction in stroke events of 36 % may have to be balanced against a 14 % increase in total mortality . Objectives To report the results of the pilot study of the Hypertension in the Very Elderly Trial ( HYVET ) , which is in progress to address these issues . Methods The HYVET-Pilot was a multicentre international open pilot trial . In 10 European countries , 1283 patients older than 80 years and with a sustained blood pressure of 160–219/90–109 mmHg were allocated r and omly to one of three treatments : a diuretic-based regimen ( usually bendroflumethiazide ; n = 426 ) , an angiotensin-converting enzyme inhibitor regimen ( usually lisinopril ; n = 431 ) or no treatment ( n = 426 ) . The procedure permitted doses of the drug to be titrated and diltiazem slow-release to be added to active treatment . Target blood pressure was < 150/80 mmHg and mean follow-up was 13 months . Results In the combined actively treated groups , the reduction in stroke events relative hazard rate ( RHR ) was 0.47 [ 95 % confidence interval ( CI ) 0.24 to 0.93 ] and the reduction in stroke mortality RHR was 0.57 ( 95 % CI 0.25 to 1.32 ) . However , the estimate of total mortality supported the possibility of excess deaths with active treatment ( RHR 1.23 , 95 % CI 0.75 to 2.01 ) . Conclusions The preliminary results support the need for the continuing main HYVET trial . It is possible that treatment of 1000 patients for 1 year may reduce stroke events by 19 ( nine non-fatal ) , but may be associated with 20 extra non-stroke deaths The Combination Therapy of Hypertension to Prevent Cardiovascular Events ( COPE ) trial demonstrated that the calcium-channel blocker benidipine-based combination therapies with an angiotensin-receptor blocker ( ARB ) , a β-blocker , or a thiazide diuretic ( thiazide ) were similarly effective in preventing cardiovascular events and achieving the target blood pressure ( BP ; < 140/90 mm Hg ) . We further evaluated the efficacy and safety of these combination therapies in older ( ⩾65 years ) and younger ( < 65 years ) hypertensive patients . In this sub- analysis of the COPE trial 3293 patients ( 1533⩾65 years old and 1760 < 65 years old ) were r and omly assigned to receive benidipine-based therapy with an ARB , a β-blocker or a thiazide . In each group , the average BP did not differ among the three treatment groups . The incidence of the primary cardiovascular composite end point in the older group was higher than in the younger group ( 12.7 vs. 8.3 per 1000 person-years , P=0.023 ) . The primary composite cardiovascular end point , achievement ( % ) of target BP , and cardiovascular hard composite end points were similar among the three treatment groups . However , the hazard ratios and 95 % confidence intervals in older patients were 2.74 ( 1.08–6.96 ; β-blocker vs. thiazide , P=0.022 ) for fatal and non-fatal stroke , and 2.47 ( 1.03–5.91 ; β-blocker vs. ARB , P=0.043 ) for new-onset diabetes . Thus , benidipine combined with an ARB , a β-blocker , or a thiazide was similarly effective in preventing cardiovascular events and achieving the target BP in both older and younger hypertensive patients . Further studies will be necessary to evaluate the usefulness of benidipine combined with a β-blocker in terms of the incidence of stroke and new-onset diabetes in older patients In this prospect i ve , r and omized , open-label , blinded end point study , we aim ed to establish whether strict blood pressure control ( < 140 mm Hg ) is superior to moderate blood pressure control ( ≥140 mm Hg to < 150 mm Hg ) in reducing cardiovascular mortality and morbidity in elderly patients with isolated systolic hypertension . We divided 3260 patients aged 70 to 84 years with isolated systolic hypertension ( sitting blood pressure 160 to 199 mm Hg ) into 2 groups , according to strict or moderate blood pressure treatment . A composite of cardiovascular events was evaluated for ≥2 years . The  strict control ( 1545 patients ) and moderate control ( 1534 patients ) groups were well matched ( mean age : 76.1 years ; mean blood pressure : 169.5/81.5 mm Hg ) . Median follow-up was 3.07 years . At 3 years , blood pressure reached 136.6/74.8 mm Hg and 142.0/76.5 mm Hg , respectively . The blood pressure difference between the 2 groups was 5.4/1.7 mm Hg . The overall rate of the primary composite end point was 10.6 per 1000 patient-years in the strict control group and 12.0 per 1000 patient-years in the moderate control group ( hazard ratio : 0.89 ; [ 95 % CI : 0.60 to 1.34 ] ; P=0.38 ) . In summary , blood pressure targets of < 140 mm Hg are safely achievable in relatively healthy patients ≥70 years of age with isolated systolic hypertension , although our trial was underpowered to definitively determine whether strict control was superior to less stringent blood pressure targets A r and omized , double-blind , active-controlled , multicenter trial assigned 32,804 participants aged 55 years and older with hypertension and ≥ 1 other coronary heart disease risk factors to receive chlorthalidone ( n=15,002 ) , amlodipine ( n=8898 ) , or lisinopril ( n=8904 ) for 4 to 8 years , when double-blinded therapy was discontinued . Passive surveillance continued for a total follow-up of 8 to 13 years using national administrative data bases to ascertain deaths and hospitalizations . During the post-trial period , fatal outcomes and nonfatal outcomes were available for 98 % and 65 % of participants , respectively , due to lack of access to administrative data bases for the remainder . This paper assesses whether mortality and morbidity differences persisted or new differences developed during the extended follow-up . Primary outcome was cardiovascular mortality and secondary outcomes were mortality , stroke , coronary heart disease , heart failure , cardiovascular disease , and end-stage renal disease . For the post-trial period , data are not available on medications or blood pressure levels . No significant differences ( P<.05 ) appeared in cardiovascular mortality for amlodipine ( hazard ratio [ HR ] , 1.00 ; 95 % confidence interval [ CI ] , 0.93 - 1.06 ) or lisinopril ( HR , 0.97 ; CI , 0.90 - 1.03 ) , each compared with chlorthalidone . The only significant differences in secondary outcomes were for heart failure , which was higher with amlodipine ( HR , 1.12 ; CI , 1.02 - 1.22 ) , and stroke mortality , which was higher with lisinopril ( HR , 1.20 ; CI , 1.01 - 1.41 ) , each compared with chlorthalidone . Similar to the previously reported in-trial result , there was a significant treatment-by-race interaction for cardiovascular disease for lisinopril vs chlorthalidone .  Black participants had higher risk than non-black participants  taking lisinopril compared with chlorthalidone . After accounting for multiple comparisons , none of these results were significant . These findings suggest that neither calcium channel blockers nor angiotensin-converting enzyme inhibitors are superior to diuretics for the long-term prevention of major cardiovascular complications of hypertension The achievement rate of blood pressure ( BP ) target and the relationship between on-treatment BP and development of cardiovascular events ( i.e. , stroke , myocardial infa rct ion , and heart failure ) were investigated in a total of 8,897 patients in the Japan 's Benidipine Research on Antihypertensive Effects in the Elderly ( J-BRAVE ) study , a prospect i ve , 3-year observational study of a  calcium channel blocker-based treatment in hypertensive patients aged ≥65 years as a post-marketing  surveillance . Blood pressure decreased significantly from 164.8 ± 14.1/88.2 ± 10.3 mmHg to 137.0 ± 13.5/75.6 ± 9.5 mmHg and the percentage of patients who achieved BP < 140/90 mmHg was 57.2 % after 3 years . The incidence of cardiovascular events was 7.54/1,000 patient-years . Subgroups of patients stratified by on-treatment systolic blood pressure ( SBP ) were analyzed . Baseline BP , body mass index ( BMI ) , the dose of benidipine , the mean number of anti-hypertensive drugs , and the incidence of cardiovascular events were higher in patients with on-treatment SBP ≥160 mmHg than in those with an SBP of < 130 mmHg . In patients aged 65 to 74 years ( n = 5,092 ) and patients aged ≥75 years ( n = 3,805 ) , the percentages of patients who achieved the BP target of < 140/90 mmHg were 57.5 % and 56.6 % after 3 years , respectively , and the incidence of cardiovascular events was higher in patients with on-treatment SBP ≥160 mmHg in both age subgroups . The results of the J-BRAVE study show that on-treatment SBP ≥160 mmHg is associated with a higher incidence of cardiovascular events in elderly hypertensive patients BACKGROUND Whether the treatment of patients with hypertension who are 80 years of age or older is beneficial is unclear . It has been suggested that antihypertensive therapy may reduce the risk of stroke , despite possibly increasing the risk of death . METHODS We r and omly assigned 3845 patients from Europe , China , Australasia , and Tunisia who were 80 years of age or older and had a sustained systolic blood pressure of 160 mm Hg or more to receive either the diuretic indapamide ( sustained release , 1.5 mg ) or matching placebo .  The angiotensin-converting-enzyme inhibitor perindopril ( 2 or 4 mg ) , or matching placebo , was added if necessary to achieve the target blood pressure of 150/80 mm Hg . The primary end point was fatal or nonfatal stroke . RESULTS The active-treatment group ( 1933 patients ) and the placebo group ( 1912 patients ) were well matched ( mean age , 83.6 years ; mean blood pressure while sitting , 173.0/90.8 mm Hg ) ; 11.8 % had a history of cardiovascular disease . Median follow-up was 1.8 years . At 2 years , the mean blood pressure while sitting was 15.0/6.1 mm Hg lower in the active-treatment group than in the placebo group . In an intention-to-treat analysis , active treatment was associated with a 30 % reduction in the rate of fatal or nonfatal stroke ( 95 % confidence interval [ CI ] , -1 to 51 ; P=0.06 ) , a 39 % reduction in the rate of death from stroke ( 95 % CI , 1 to 62 ; P=0.05 ) , a 21 % reduction in the rate of death from any cause ( 95 % CI , 4 to 35 ; P=0.02 ) , a 23 % reduction in the rate of death from cardiovascular causes ( 95 % CI , -1 to 40 ; P=0.06 ) , and a 64 % reduction in the rate of heart failure ( 95 % CI , 42 to 78 ; P<0.001 ) . Fewer serious adverse events were reported in the active-treatment group ( 358 , vs. 448 in the placebo group ; P=0.001 ) . CONCLUSIONS The results provide evidence that antihypertensive treatment with indapamide ( sustained release ) , with or without perindopril , in persons 80 years of age or older is beneficial . ( Clinical Trials.gov number , NCT00122811 [ Clinical Trials.gov ] . ) 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 BACKGROUND Observational epidemiological studies have shown a positive association between hypertension and risk of incident dementia ; however , the effects of antihypertensive therapy on cognitive function in controlled trials have been conflicting , and meta-analyses of the trials have not provided clear evidence of whether antihypertensive treatment reduces dementia incidence . The Hypertension in the Very Elderly trial ( HYVET ) was design ed to assess the risks and benefits of treatment of hypertension in elderly patients and included an assessment of cognitive function . METHODS Patients with hypertension ( systolic pressure 160 - 200 mm Hg ; diastolic pressure < 110 mm Hg ) who were aged 80 years or older were enrolled in this double-blind , placebo-controlled trial . Participants were r and omly assigned to receive 1.5 mg slow release indapamide , with the option of 2 - 4 mg perindopril , or placebo . The target systolic blood pressure was 150 mm Hg ; the target diastolic blood pressure was 80 mm Hg . Participants had no clinical diagnosis of dementia at baseline , and cognitive function was assessed at baseline and annually with the mini-mental state examination ( MMSE ) . Possible cases of incident dementia ( a fall in the MMSE score to < 24 points or a drop of three points in 1 year ) were assessed by st and ard diagnostic criteria and expert review . The trial was stopped in 2007 at the second interim analysis after treatment result ed in a reduction in stroke and total mortality . Analysis was by intention to treat . The trial is registered with Clinical Trials.gov , number NCT00122811 . FINDINGS 3336 HYVET participants had at least one follow-up assessment ( mean 2.2 years ) and were included : 1687 participants were r and omly assigned to the treatment group and 1649 to the placebo group . Only five reports of adverse effects were attributed to the medication : three in the placebo group and two in the treatment group . The mean decrease in systolic blood pressure between the treatment and placebo groups at 2 years was systolic -15 mm Hg , p<0.0001 ; and diastolic -5.9 mm Hg , p<0.0001 . There were 263 incident cases of dementia . The rates of incident dementia were 38 per 1000 patient-years in the placebo group and 33 per 1000 patient-years in the treatment group . There was no significant difference between treatment and placebo groups ( hazard ratio [ HR ] 0.86 , 95 % CI 0.67 - 1.09 ) ; however , when these data were combined in a meta- analysis with other placebo-controlled trials of antihypertensive treatment , the combined risk ratio favoured treatment ( HR 0.87 , 0.76 - 1.00 , p=0.045 ) . INTERPRETATION Antihypertensive treatment  in elderly patients does not statistically reduce incidence of dementia . This negative finding might have been due to the short follow-up , owing to the early termination of the trial , or the modest effect of treatment . Nevertheless , the HYVET findings , when included in a meta- analysis , might support antihypertensive treatment to reduce incident dementia Abstract Background : In Japan , when pharmaceutical companies launch a new drug , they are obligated to conduct a post-marketing survey to evaluate the safety and efficacy of the drug in accordance with Good Post-Marketing Surveillance Practice under Article 14 - 4 ( re-examination ) of the Pharmaceutical Affairs Law at contracted medical institutions . We report the results of a long-term special survey that we conducted as a post-marketing survey . Objective : The results of a prospect i ve post-marketing survey that was conducted to assess the safety and efficacy of the b-adrenergic receptor antagonist ( β-blocker ) Artist ® tablets 10 mg , 20 mg ( carvedilol ) in patients with hypertension in Japan , were investigated in order to examine the safety and efficacy of the drug during long-term treatment ( 18 months ) . Patients : Patients were carvedilol-naive and had essential hypertension or renal parenchymal hypertension . Methods : We performed this survey as a prospect i ve cohort study ( special survey ) utilizing a central ized registration method over 3 years ( starting from April 1994 ) , for an observation period of 18 months of carvedilol treatment . Results : Sixty-one medical institutions across Japan collected 380 case report forms of patients who received long-term administration of carvedilol , with 363 and 341 cases evaluated for safety and efficacy , respectively . The discontinuation rate was 7.2 % and the incidence of adverse drug reactions was 5.23 % ( 19 of 363 ) in the safety population . There was no significant change in fasting plasma glucose levels from baseline ( 118.1 ± 46.5mg/dL ) to after carvedilol treatment ( 114.6 ± 43.3 mg/dL ) [ n = 141 ; p = 0.310].In 341 evaluable patients in the efficacy population , decreases in both blood pressure and pulse rate were statistically significant at all assessment points in comparison with baseline data ( p < 0.001 ) . Similarly , in hypertensive patients with diabetes  mellitus , decreases in blood pressure were statistically significant at all assessment points in comparison with baseline data ( p < 0.001 ) . Conclusions : The results of this study show that carvedilol exerted stable antihypertensive effects leading to favorable blood pressure control throughout long-term treatment , without showing any safety concerns . It was concluded that there were no clinical ly significant issues in terms of safety or efficacy with the long-term treatment of carvedilol in patients with hypertension OBJECTIVES The aim of this study was to test the hypothesis that the angiotensin II type 1 receptor blocker ( ARB ) c and esartan can reduce the risk of stroke in elderly patients with isolated systolic hypertension ( ISH ) . BACKGROUND Isolated systolic hypertension is the predominant form of hypertension in the elderly , and stroke is the most common cardiovascular ( CV ) complication . METHODS In the Study on Cognition and Prognosis in the Elderly ( SCOPE ) , 4,964 patients age 70 to 89 years were r and omly assigned to double-blind c and esartan or placebo with open-label antihypertensive therapy ( mostly thiazide diuretics ) added as needed to control blood pressure . Of the 4,964 patients , 1,518 had ISH ( systolic blood pressure > 160 mm Hg and diastolic blood pressure < 90 mm Hg ) . The present study is a predefined subgroup analysis of outcome results in the ISH patients . RESULTS Of the ISH patients , 754 were r and omized to the c and esartan group and 764 to the control group . Over the study period , blood pressure was reduced by 22/6 mm Hg in the c and esartan group and by 20/5 mm Hg in the control group ( difference between treatments 2/1 mm Hg ; p = 0.101 and 0.064 ) . A total of 20 fatal/non-fatal strokes occurred in the c and esartan group ( 7.2/1,000 patient-years ) and 35 in the control group ( 12.5/1,000 patient-years ) ; relative risk ( RR ) was 0.58 ( 95 % confidence interval 0.33 to 1.00 ) , that is , a RR reduction of 42 % ( p = 0.050 unadjusted , p = 0.049 adjusted for baseline risk ) . There were no marked or statistically significant differences between the treatment groups in other CV end points or all-cause mortality . CONCLUSIONS In elderly patients with ISH , antihypertensive treatment based on the ARB c and esartan result ed in a significant 42 % RR reduction in stroke in comparison with other antihypertensive treatment , despite little difference in blood pressure reduction Background The prognostic benefits of blood pressure lowering treatment in elderly hypertensive patients were established more than a decade ago , but are less clear in those with mildly to moderately elevated blood pressure . Objective To assess whether c and esartan-based antihypertensive treatment in elderly patients with mildly to moderately elevated blood pressure confers a reduction in cardiovascular events , cognitive decline and dementia . Design Prospect i ve , double-blind , r and omized , parallel-group study conducted in 1997–2002 . Setting and participants The study was of 4964 patients aged 70–89 years , with systolic blood pressure 160–179 mmHg , and /or diastolic blood pressure 90–99 mmHg , and a Mini Mental State Examination ( MMSE ) test score ⩾ 24 . A total of 527 centres in 15 countries participated in the study . Intervention Patients were assigned r and omly to receive the angiotensin receptor blocker c and esartan or placebo , with open-label active antihypertensive therapy added as needed . As a consequence , active antihypertensive therapy was extensively used in the control group ( 84 % of patients ) . Mean follow-up was 3.7 years . Main outcome measures The primary outcome measure was major cardiovascular events , a composite of cardiovascular death , non-fatal stroke and non-fatal myocardial infa rct ion . Secondary outcome measures included cardiovascular death , non-fatal and fatal stroke and myocardial infa rct ion , cognitive function measured by the MMSE and dementia . Results Blood pressure fell by 21.7/10.8 mmHg in the c and esartan group and by 18.5/9.2 mmHg in the control group . A first major cardiovascular event occurred in 242 c and esartan patients and in 268 control patients ; risk reduction with c and esartan was 10.9 % [ 95 % confidence interval ( CI ) , −6.0 to 25.1 , P = 0.19 ] . C and esartan-based treatment reduced non-fatal stroke by 27.8 % ( 95 % CI , 1.3 to 47.2 , P = 0.04 ) , and all stroke by 23.6 % ( 95 % CI , −0.7 to 42.1 , P = 0.056 ) . There were no significant differences in myocardial infa rct ion and cardiovascular mortality . Mean MMSE score fell from 28.5 to 28.0 in the c and esartan group and from 28.5 to 27.9 in the control group ( P = 0.20 ) . The proportions of patients who had a significant cognitive decline or developed dementia were not different in the two treatment groups . Conclusions In elderly hypertensive patients , a slightly more effective blood pressure reduction during c and esartan-based therapy , compared with control therapy , was associated with a modest , statistically non-significant , reduction in major cardiovascular events and with a marked reduction in non-fatal stroke . Cognitive function was well maintained in both treatment groups in the presence of substantial blood pressure reductions . Both treatment regimens were generally well tolerated Objective : To compare the blood pressure‐lowering efficacy , the frequency of side effects and changes in laboratory values of three & bgr;‐blockers and a potassium‐sparing diuretic combination in elderly hypertensive patients . Design : The Swedish Trial in Old Patients with Hypertension ( STOP‐Hypertension ) was a prospect i ve , r and omized , double‐blind , multicentre trial comparing active antihypertensive treatment with placebo in patients aged 70‐84 years . Methods : The study group consisted of 1627 elderly hypertensive patients ( mean ± SD age 75.7 ± 3.7 years ; 37 % males , 63 % females ) . Supine and st and ing blood pressure , heart rate and side effects were recorded at each visit . Blood was drawn for routine analysis . The mean length of follow‐up was 25 months ( range 6‐65 ) . No patient was lost to follow‐up . Results : After 2‐months ' single‐drug therapy , all four active drugs were found to be equally effective in reducing diastolic blood pressure ( DBP ) . However , there were differences in their efficacy in reducing systolic blood pressure ( SBP ) ; the diuretic was significantly more effective than the & bgr;‐receptor blockers . The results of a series of multiple linear regression analyses showed that the observed differences in effect on SBP could not be explained by the different effects of the drugs on heart rate . More than two‐thirds of the patients were given supplementary treatment , most of them already by the 2‐month visit , after which there was no significant difference in blood pressure among the treatment regimens . The changes in laboratory values and in the prevalence of symptoms were minor for all four regimens . Conclusion : Metoprolol ( controlled release ) , atenolol , pindolol and the combination hydrochlorothiazide + amiloride were equally effective as single drugs in reducing DBP . There were differences in their efficacy in reducing SBP , the diuretic being more effective than the & bgr;‐blockers . After addition of supplementary treatment ( & bgr;‐blocker to diuretic , or vice versa ) there were no significant differences in blood pressure reduction among the groups . The changes in laboratory values and in the prevalence of symptoms were minor for all active treatment regimens . Thus , the satisfactory effect on cardiovascular morbidity and mortality was not impaired by low tolerability of the drugs Objective : To perform a subgroup analysis on those patients in STOP‐Hypertension‐2 who had isolated systolic hypertension . Design and methods : The STOP‐Hypertension‐2 study evaluated cardiovascular mortality and morbidity in elderly hypertensives comparing treatment with conventional drugs ( diuretics , beta‐blockers ) with that of newer ones [ angiotensin‐converting enzyme ( ACE ) inhibitors , calcium antagonists ] . In all , 6614 elderly patients with hypertension ( mean age 76.0 years , range 70–84 years at baseline ) were included in STOP‐Hypertension‐2 . In the present subgroup analysis of STOP‐Hypertension‐2 , isolated systolic hypertension was defined as systolic blood pressure at least 160 mmHg and diastolic blood pressure below 95 mmHg , in accordance with the Syst‐Eur and Syst‐China study criteria . In total , 2280 patients in STOP‐Hypertension‐2 met these criteria . In the study , patients were r and omized to one of three treatment groups : “ conventional ” antihypertensive therapy with beta‐blockers or diuretics ( atenolol 50 mg , metoprolol 100 mg , pindolol 5 mg , or fixed‐ratio hydrochlorothiazide 25 mg plus amiloride 2.5 mg daily ) ; ACE inhibitors ( enalapril 10 mg or lisinopril 10 mg daily ) ; or calcium antagonists ( felodipine 2.5 mg or isradipine 2.5 mg daily ) . Analysis was by intention to treat . Results : The blood pressure lowering effect in patients with systolic hypertension was similar with all three therapeutic regimens : 35/13 mmHg in the conventional group ( n = 717 ) , 34/12 mmHg in the ACE inhibitor group ( n = 724 ) , and 35/13 mmHg in the calcium antagonist group ( n = 708 ) . Prevention of cardiovascular mortality , the primary endpoint of the study , did not differ between the three treatment groups . All stroke events , i.e. fatal and non‐fatal stroke together , were significantly reduced by 25 % in the newer‐drugs group compared with the conventional group ( 95 % CI 0.58–0.97 ; p = 0.027 ) . This difference was attributable to reduction of non‐fatal stroke while fatal stroke events did not differ between groups . New cases of atrial fibrillation were significantly increased by 43 % ( 95 % CI 1.02–1.99 ; p = 0.037 ) on “ newer ” drugs compared with “ conventional ” therapy , mainly attributable to the calcium antagonists . There were no significant differences between the three treatment groups with respect to the risks of myocardial infa rct ion , sudden death or congestive heart failure . Conclusions : The analysis demonstrated that “ newer ” therapy ( ACE inhibitors/calcium antagonists ) was significantly better ( 25 % ) than “ conventional ” ( diuretics/beta‐blockers ) in preventing all stroke in elderly patients with isolated systolic hypertension 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 The benefits of lowering a systolic blood pressure below 140 mmHg in elderly hypertension remain controversial . This study is a prospect i ve , r and omized , open-label study with blinded assessment of endpoints to compare the 2-year effect of strict treatment to maintain systolic blood pressure below 140 mmHg with that of mild treatment to maintain systolic blood pressure below 160 but at or above 140 mmHg in elderly hypertensive patients . Patients with essential hypertension ( 65–85 years old , with a pretreatment systolic blood pressure of above 160 mmHg ) were r and omly assigned to receive strict treatment ( n=2,212 ) or mild treatment ( n=2,206 ) . The baseline drug was efonidipine hydrochloride , a long-acting calcium antagonist . The primary endpoint was the combined incidence of cardiovascular disease and renal failure , and the secondary endpoints were total deaths and any safety problems . Although final blood pressures ( systolic/diastolic ) were significantly lower in the strict-treatment group compared with the mild-treatment group ( 135.9/74.8 vs. 145.6/78.1 mmHg ; p<0.001 ) , the incidence of the primary endpoint was similar in the two groups ( 86 patients in each group ; p=0.99 ) . Total deaths were 54 in the strict-treatment group vs. 42 in the mild-treatment group ( p=0.22 ) , and treatment was withdrawn because of adverse events in 36 patients in each group ( p=0.99 ) . An interaction between age and treatment for the primary endpoints ( p=0.03 ) was seen . Complex clinical features associated with aging seem to have obscured the difference in effect between the two treatments . Further studies are needed to assess the optimal treatment strategy for hypertension in the elderly BACKGROUND Is cancer related to hypertension and blood pressure ? Do antihypertensive drugs promote cancer ? Do antihypertensive drugs protect against cancer ? We previously analysed the frequency of  cardiovascular mortality and morbidity in elderly people who participated in the Swedish Trial in Old Patients with Hypertension 2 ( STOP-Hypertension-2 ) . We have also looked at the frequency of cancer in these patients . METHODS We r and omly assigned 6614 elderly patients with hypertension ( mean age 76 years , median time of follow-up 5.3 years ) to one of three treatment strategies : conventional drugs ( diuretics or b-blockers ) , calcium antagonists , or ACE inhibitors . We matched the patients to the Swedish Cancer Registry and compared our findings with expected values based on age , sex , and calendar-year-specific reference frequencies for the general Swedish population . We also compared the number of cancers between the three treatment groups . FINDINGS At baseline , 607 ( 9 % ) patients had previous malignant disease . Diagnoses were closely similar to the distribution of cancer types that might be seen in elderly patients . During follow-up , there were 625 new cases of cancer in 590 patients . The frequency of cancer did not differ significantly between the treatment strategies , including all cancers and those at individual sites . The st and ardised incidence ratios ( SIRs ) for all cancers were also close to unity : 0.92 ( 95 % CI 0.80 - 1.06 ) for conventional drugs , 0.96 ( 0.83 - 1.10 ) for calcium antagonists , and 0.99 ( 0.86 - 1.13 ) for ACE inhibitors . INTERPRETATIONS No difference in cancer risk was seen between patients r and omly assigned to conventional drugs , calcium antagonists , or ACE inhibitors . Thus , the general message to the practising physician is that more attention should be given to getting the blood pressure down than to the risk of cancer Background The benefits of treating hypertension in elderly diabetic patients , in terms of achieving reductions in cardiovascular morbidity and mortality , have been documented in several recent prospect i ve trials . There has , however , been some controversy regarding the effect of different antihypertensive drugs on the frequency of myocardial infa rct ion in this group of patients . Design STOP Hypertension-2 was a prospect i ve , r and omized , open trial with blinded endpoint evaluation . Methods We studied 6614 elderly patients aged 70–84 years ; 719 of them had diabetes mellitus at the start of the study ( mean age 75.8 years ) . Patients were r and omly assigned to one of three treatment strategies : conventional antihypertensive drugs ( diuretics or β-blockers ) , calcium antagonists , or angiotensin converting enzyme ( ACE ) inhibitors . Results Reduction in blood pressure was similar in the three treatment groups of diabetics . The prevention of cardiovascular mortality was also similar ; the frequency of this primary endpoint did not differ significantly between the three groups . There were , however , significantly fewer ( P = 0.025 ) myocardial infa rct ions during ACE inhibitor treatment ( n = 17 ) than during calcium antagonist treatment ( n = 32 ; relative risk 0.51 , 95 % confidence interval 0.28–0.92 ) ; but a ( non-significant ) tendency to more strokes during ACE inhibitor treatment ( n = 34 compared with n = 29 ; relative risk 1.16 , 95 % confidence interval 0.71–1.91 ) . Conclusion Treatment of hypertensive diabetic patients with conventional antihypertensive drugs ( diuretics , β-blockers , or both ) seemed to be as effective as treatment with newer drugs such as calcium antagonists or ACE inhibitors BACKGROUND fractures may have serious implication s in an elderly individual , and fracture prevention may include a careful choice of medications . DESIGN the Hypertension in the Very Elderly Trial ( HYVET ) was a double-blind placebo-controlled trial of a thiazide-like diuretic ( indapamide 1.5 mg SR ) with the optional addition of the angiotensin-converting enzyme ( ACE ) inhibitor ( perindopril 2 - 4 mg ) . Fracture was a secondary end point of the trial . SETTING HYVET recruited participants from Eastern and Western Europe , China , Australasia , and Tunisia . SUBJECTS all participants were > or = 80 years of age and hypertensive . METHODS participants were r and omised to receive a thiazide-like diuretic ( indapamide 1.5 mg SR ) + /- ACE inhibitor ( perindopril 2 - 4 mg ) or matching placebos .  Incident fractures were vali date d and analysed based on time to first fracture . RESULTS there were 3,845 participants in HYVET and a total 102 reported fractures  ( 42 in the active and 60 in the placebo group ) . When taking only vali date d first fractures , 90 were included in the analyses ( 38 in the active and 52 in the placebo group ) . Cox proportional hazard regression , adjusted for key baseline risk factors , result ed in a point estimate of 0.58 ( 95 % CI 0.33 - 1.00 , P = 0.0498 ) . CONCLUSIONS despite the lowering of blood pressure , treatment with a thiazide-like diuretic and an ACE inhibitor does not increase and may decrease fracture rate OBJECTIVE --To establish whether treatment with diuretic or beta blocker in hypertensive older adults reduces risk of stroke , coronary heart disease , and death . DESIGN --R and omised , placebo controlled , single blind trial . SETTING --226 general practice s in the MRC general practice research framework . SUBJECTS--4396 patients aged 65 - 74 r and omised to receive diuretic , beta blocker , or placebo . Patients had mean systolic pressures of 160 - 209 mm Hg and mean diastolic pressures less than 115 mm Hg during an eight week run in and were not taking antihypertensive treatment . INTERVENTION-- Patients were r and omised to atenolol 50 mg daily ; hydrochlorothiazide 25 mg or 50 mg plus amiloride 2.5 mg or 5 mg daily ; or placebo . The regimens were adjusted to achieve specified target pressures . Mean follow up was 5.8 years . MAIN OUTCOME MEASURES --Strokes , coronary events , and deaths from all causes . RESULTS --Both treatments reduced blood pressure below the level in the placebo group . Compared with the placebo group , actively treated subjects ( diuretic and beta blocker groups combined ) had a 25 % ( 95 % confidence interval 3 % to 42 % ) reduction in stroke ( p = 0.04 ) , 19 % ( -2 % to 36 % ) reduction in coronary events ( p = 0.08 ) , and 17 % ( 2 % to 29 % ) reduction in all cardiovascular events ( p = 0.03 ) . After adjusting for baseline characteristics the diuretic group had significantly reduced risks of stroke ( 31 % ( 3 % to 51 % ) p = 0.04 ) , coronary events ( 44 % ( 21 % to 60 % ) , p = 0.0009 ) , and all cardiovascular events ( 35 % ( 17 % to 49 % ) , p = 0.0005 ) compared with the placebo group . The beta blocker group showed no significant reductions in these end points . The reduction in strokes was mainly in non-smokers taking the diuretic . CONCLUSION --Hydrochlorothiazide and amiloride reduce the risk of stroke , coronary events , and all cardiovascular events in older hypertensive adults The Hypertension Optimal Treatment ( HOT ) Study is an ongoing prospect i ve , r and omized , multicenter trial conducted in 26 countries . Its two main aims are to evaluate the relationship between three levels of target diastolic blood pressure ( < or = 90 , < or = 85 or < or = 80 mmHg ) and the incidence of cardiovascular morbidity and mortality in hypertensive patients and the effects on morbidity and mortality of a low dose , 75 mg daily , of acetylsalicylic acid ( ASA , aspirin ) compared with placebo .  Altogether 19,193 patients have been recruited and r and omized and one-year data are now available for all patients . This is a report on the blood pressures achieved , the tolerability and other available data after 12 months of follow-up of all patients . Special reference will be given to the subgroup of elderly patients ( > or = 65 years , n = 6,113 ) as compared to younger patients ( < 65 years , n = 13,080 ) . On average , the target group < or = 90 mmHg in diastolic blood pressure has reached 86 mmHg , the target group < or = 85 mmHg has reached 83 mmHg and the target group < or = 80 mmHg has reached 81 mmHg . The percentage of patients that has obtained their target blood pressures is 84 % in the target group < or = 90 mmHg , 72 % in the target group < or = 85 mmHg and 57 % in the target group < or = 80 mmHg at 12 months of follow-up . In the elderly subgroup ( > or = 65 years of age ) the percentage of patients at target is higher for all target groups , being 86 , 76 and 61 % , respectively , at 12 months . Antihypertensive treatment is initiated with a calcium antagonist , felodipine , at a dose of 5 mg once daily . If target blood pressure is not reached , additional antihypertensive therapy , with either an angiotensin converting enzyme ( ACE ) inhibitor or a beta-adrenoceptor blocking agent , is given . Further dose adjustments are made in accordance with a set protocol . As a fifth and final step a diuretic may be added . Side effects have been relatively few in this large multinational series of intensively treated hypertensive patients . Only ankle edema , 2.6 % and 3.0 % , and coughing , 1.3 % and 0.8 % , in young and elderly patients , respectively , exceed a frequency of 1 % , and 88 % of all patients are still taking their baseline therapy felodipine after one year . The one-year data presented here indicate that it should be possible to fulfill the primary aims of the HOT Study BACKGROUND It is unknown whether high-dose angiotensin II receptor blocker therapy or angiotensin II receptor blocker + calcium channel blocker combination therapy is better in elderly hypertensive patients with high cardiovascular risk . The objective of the study was to compare the efficacy of these treatments in elderly , high-risk Japanese hypertensive patients . METHODS The OlmeSartan and Calcium Antagonists R and omized ( OSCAR ) study was a multicenter , prospect i ve , r and omized , open-label , blinded-end point study of 1164 hypertensive patients aged 65 to 84 years with type 2 diabetes or cardiovascular disease . Patients with uncontrolled hypertension during treatment with olmesartan 20 mg/d were r and omly assigned to receive 40 mg/d olmesartan ( high-dose angiotensin II receptor blocker ) or a calcium channel blocker + 20 mg/d olmesartan ( angiotensin II receptor blocker + calcium channel blocker ) . The primary end point was a composite of cardiovascular events and noncardiovascular death . RESULTS During a 3-year follow-up , blood pressure was significantly lower in the angiotensin II receptor blocker + calcium channel blocker group than in the high-dose angiotensin II receptor blocker group . Mean blood pressure at 36 months was 135.0/74.3 mm Hg in the high-dose angiotensin II receptor blocker group and 132.6/72.6 mm Hg in the angiotensin II receptor blocker + calcium channel blocker group . More primary end points occurred in the high-dose angiotensin II receptor blocker group than in the angiotensin II receptor blocker + calcium channel blocker group ( 58 vs 48 events , hazard ratio [ HR ] , 1.31 , 95 % confidence interval , 0.89 - 1.92 ; P=.17 ) . In patients with cardiovascular disease at baseline , more primary events occurred in the high-dose angiotensin II receptor blocker group ( HR , 1.63 , P=.03 ) ; in contrast , fewer events were observed in the subgroup without cardiovascular disease ( HR , 0.52 , P=.14 ) . This treatment-by-subgroup interaction was significant ( P=.02 ) . CONCLUSION The angiotensin II receptor blocker and calcium channel blocker combination lowered blood pressure more than the high-dose angiotensin II receptor blocker and reduced the incidence of primary end points more than the high-dose angiotensin II receptor blocker in patients with cardiovascular disease . The addition of a second antihypertensive agent is more effective at lowering blood pressure than simply doubling the dose of an existing agent ABCD : Appropriate Blood pressure Control in Diabetes ABI : ankle – brachial index ABPM : ambulatory blood pressure monitoring ACCESS : Acute C and esartan Cilexetil Therapy in Stroke Survival ACCOMPLISH : Avoiding Cardiovascular Events in Combination Therapy in Patients Living with Systolic Hypertension ACCORD : Action to Control Cardiovascular Risk in Diabetes ACE : angiotensin-converting enzyme ACTIVE I : Atrial Fibrillation Clopidogrel Trial with Irbesartan for Prevention of Vascular Events ADVANCE : Action in Diabetes and Vascular Disease : Preterax and Diamicron-MR Controlled Evaluation AHEAD : Action for HEAlth in Diabetes ALLHAT : Antihypertensive and Lipid-Lowering Treatment to Prevent Heart ATtack ALTITUDE : ALiskiren Trial In Type 2 Diabetes Using Cardio-renal Endpoints ANTIPAF : ANgioTensin II Antagonist In Paroxysmal Atrial Fibrillation APOLLO : A R and omized Controlled Trial of Aliskiren in the Prevention of Major Cardiovascular Events in Elderly People ARB : angiotensin receptor blocker ARIC : Atherosclerosis Risk In Communities ARR : aldosterone renin ratio ASCOT : Anglo-Sc and inavian Cardiac Outcomes Trial ASCOT-LLA : Anglo-Sc and inavian Cardiac Outcomes Trial — Lipid Lowering Arm ASTRAL : Angioplasty and STenting for Renal Artery Lesions A-V : atrioventricular BB : beta-blocker BMI : body mass index BP : blood pressure BSA : body surface area CA : calcium antagonist CABG : coronary artery bypass graft CAPPP : CAPtopril Prevention Project CAPRAF : C And esartan in the Prevention of Relapsing Atrial Fibrillation CHD : coronary heart disease CHHIPS : Controlling Hypertension and Hypertension Immediately Post-Stroke CKD : chronic kidney disease CKD-EPI : Chronic Kidney Disease — EPIdemiology collaboration CONVINCE : Controlled ONset Verapamil INvestigation of CV Endpoints CT : computed tomography CV : cardiovascular CVD : cardiovascular disease D : diuretic DASH : Dietary Approaches to Stop Hypertension DBP : diastolic blood pressure DCCT : Diabetes Control and Complications Study DIRECT : DIabetic REtinopathy C and esartan Trials DM : diabetes mellitus DPP-4 : dipeptidyl peptidase 4 EAS : European Atherosclerosis Society EASD : European Association for the Study of Diabetes ECG : electrocardiogram EF : ejection fraction eGFR : estimated glomerular filtration rate ELSA : European Lacidipine Study on Atherosclerosis ESC : European Society of Cardiology ESH : European Society of Hypertension ESRD : end-stage renal disease  EXPLOR : Amlodipine – Valsartan Combination Decreases Central Systolic Blood Pressure more Effectively than the Amlodipine – Atenolol Combination FDA : U.S. Food and Drug Administration FEVER : Felodipine EVent Reduction study GISSI-AF : Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico-Atrial Fibrillation HbA1c : glycated haemoglobin HBPM : home blood pressure monitoring HOPE : Heart Outcomes Prevention Evaluation HOT : Hypertension Optimal Treatment HRT : hormone replacement therapy HT : hypertension HYVET : HYpertension in the Very Elderly Trial IMT : intima-media thickness I-PRESERVE : Irbesartan in Heart Failure with Preserved Systolic Function INTERHEART : Effect of Potentially Modifiable Risk Factors associated with Myocardial Infa rct ion in 52 Countries INVEST : INternational VErapamil SR/T Tr and olapril ISH : Isolated systolic hypertension JNC : Joint National Committee JUPITER : Justification for the Use of Statins in Primary Prevention : an Intervention Trial Evaluating Rosuvastatin LAVi : left atrial volume index LIFE : Losartan Intervention For Endpoint Reduction in Hypertensives LV : left ventricle/left ventricular LVH : left ventricular hypertrophy LVM : left ventricular mass MDRD : Modification of Diet in Renal Disease MRFIT : Multiple Risk Factor Intervention Trial MRI : magnetic resonance imaging NORDIL : The Nordic Diltiazem Intervention study OC : oral contraceptive OD : organ damage ONTARGET : ONgoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial PAD : peripheral artery disease PATHS : Prevention And Treatment of Hypertension Study PCI : percutaneous coronary intervention PPAR : peroxisome proliferator-activated receptor PREVEND : Prevention of REnal and Vascular ENdstage Disease PROFESS : Prevention Regimen for Effectively Avoiding Secondary Strokes PROGRESS : Perindopril Protection Against Recurrent Stroke Study PWV : pulse wave velocity QALY : Quality adjusted life years RAA : renin-angiotensin-aldosterone RAS : renin-angiotensin system RCT : r and omized controlled trials RF : risk factor ROADMAP : R and omized Olmesartan And Diabetes MicroAlbuminuria Prevention SBP : systolic blood pressure SCAST : Angiotensin-Receptor Blocker C and esartan for Treatment of Acute STroke SCOPE : Study on COgnition and Prognosis in the Elderly SCORE : Systematic COronary Risk Evaluation SHEP : Systolic Hypertension in the Elderly Program STOP : Swedish Trials in Old Patients with Hypertension STOP-2 : The second Swedish Trial in Old Patients with Hypertension SYSTCHINA : SYSTolic Hypertension in the Elderly : Chinese trial SYSTEUR : SYSTolic Hypertension in Europe TIA : transient ischaemic attack TOHP : Trials Of Hypertension Prevention TRANSCEND : Telmisartan R and omised AssessmeNt Study in ACE iNtolerant subjects with cardiovascular Disease UKPDS : United Kingdom Prospect i ve Diabetes Study VADT : Veterans ' Affairs Diabetes Trial VALUE : Valsartan Antihypertensive Long-term Use Evaluation WHO : World Health Organization # # # 1.1 Principles The 2013 guidelines on hypertension of the European Society of Hypertension ( ESH ) and the European Society of Cardiology Hypertension is the most common condition seen in primary care and leads to myocardial infa rct ion , stroke , renal failure , and death if not detected early and treated appropriately . Patients want to be assured that blood pressure ( BP ) treatment will reduce their disease burden , while clinicians want guidance on hypertension management using the best scientific evidence . This report takes a rigorous , evidence -based approach to recommend treatment thresholds , goals , and medications in the management of hypertension in adults . Evidence was drawn from r and omized controlled trials , which represent the gold st and ard for determining efficacy and effectiveness . Evidence quality and recommendations were grade d based on their effect on important outcomes . There is strong evidence to support treating hypertensive persons aged 60 years or older to a  BP goal  of less than 150/90 mm Hg and hypertensive persons 30 through 59 years of age to a diastolic goal of less than 90 mm Hg ; however , there is insufficient evidence in hypertensive persons younger than 60 years for a systolic goal , or in those younger than 30 years for a diastolic goal , so the panel recommends a BP of less than 140/90 mm Hg for those groups based on expert opinion . The same thresholds and goals are recommended for hypertensive adults with diabetes or nondiabetic chronic kidney disease ( CKD ) as for the general hypertensive population younger than 60 years . There is moderate evidence to support initiating drug treatment with an angiotensin-converting enzyme inhibitor , angiotensin receptor blocker , calcium channel blocker , or thiazide-type diuretic in the nonblack hypertensive population , including those with diabetes . In the black hypertensive population , including those with diabetes , a calcium channel blocker or thiazide-type diuretic is recommended as initial therapy . There is moderate evidence to support initial or add-on antihypertensive therapy with an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker in persons with CKD to improve kidney outcomes . Although this guideline provides evidence -based recommendations for the management of high BP and should meet the clinical needs of most patients , these recommendations are not a substitute for clinical judgment , and decisions about care must carefully consider and incorporate the clinical characteristics and circumstances of each individual patient
target: Strict control [ systolic BP ( SBP ) < 140 mmHg ] was not consistently better than mild control ( SBP < 150 mmHg ) for adults aged ≥65 years .
  Mild SBP control benefitted subjects in all age ranges over 65 years .
  Conclusions In this review , older adults with hypertension had decreased cardiovascular morbidity and mortality  with antihypertensives compared with no treatment .
  Strict control was not consistently better than mild control in older adults .
  The current evidence is insufficient to determine the safest , most beneficial hypertension regimen in older adults
background: Background Hypertension increases with increasing age .
  Optimal treatment of hypertension is important to reduce cardiovascular disease .
  Recent guidelines for hypertension have made recommendations for older adults but are supported by evidence that includes younger individuals .
  This systematic review evaluates the benefits and harms of antihypertensive agents in adults aged ≥65 years .