title: Effects of Angiotensin-Converting Enzyme Inhibition in Low-Risk Patients Early After Coronary Artery Bypass Surgery Effect of long-acting nifedipine on mortality and cardiovascular morbidity in patients with stable angina requiring treatment (ACTION trial): randomised controlled trial Randomized, placebo-controlled trial of the angiotensin-converting enzyme inhibitor, ramipril, in patients with coronary or other occlusive arterial disease. PART-2 Collaborative Research Group. Prevention of Atherosclerosis with Ramipril. Blood pressure and outcomes in very old hypertensive coronary artery disease patients: an INVEST substudy. Efficacy of perindopril in reduction of cardiovascular events among patients with stable coronary artery disease: randomised, double-blind, placebo-controlled, multicentre trial (the EUROPA study). Angiotensin-converting-enzyme inhibition in stable coronary artery disease. 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 — Early after  coronary artery bypass surgery ( CABG ) , activation of numerous neurohumoral and endogenous vasodilator systems occurs that could be influenced favorably by angiotensin-converting enzyme inhibitors . Methods and Results — The Ischemia Management with Accupril post – bypass Graft via Inhibition of the coNverting Enzyme ( IMAGINE ) trial tested whether early initiation ( ≤7 days ) of an angiotensin-converting enzyme inhibitor after CABG reduced cardiovascular events in stable patients with left ventricular ejection fraction ≥40 % . The trial was a double-blind , placebo-controlled study of 2553 patients r and omly assigned to quinapril , target dose 40 mg/d , or placebo , who were followed up to a maximum of 43 months . The mean ( SD ) age was 61 ( 10 ) years . The incidence of the primary composite end point ( cardiovascular death , resuscitated cardiac arrest , nonfatal myocardial infa rct ion , coronary revascularization , unstable angina or heart failure requiring hospitalization , documented angina , and stroke ) was 13.7 % in the quinapril group and 12.2 % in the placebo group ( hazard ratio 1.15 , 95 % confidence interval 0.92 to 1.42 , P=0.212 ) over a median follow-up of 2.95 years . The incidence of the primary composite end point increased significantly in the first 3 months after CABG in the quinapril group ( hazard ratio 1.52 , 95 % confidence interval 1.03 to 2.26 , P=0.0356 ) . Adverse events also increased in the quinapril group , particularly during the first 3 months after CABG . Conclusions — In patients at low risk of cardiovascular events after CABG , routine early initiation of angiotensin-converting enzyme inhibitor therapy does not appear to improve clinical outcome up to 3 years after CABG ; however , it increases the incidence of adverse events , particularly early after CABG . Thus , early after CABG , initiation of angiotensin-converting enzyme inhibitor therapy should be individualized and continually reassessed over time according to risk BACKGROUND Calcium antagonists are widely prescribed for angina pectoris but their effect on clinical outcome is controversial . We aim ed to investigate the effect of the calcium antagonist nifedipine on long-term outcome in patients with stable angina pectoris . METHODS We r and omly assigned 3825 patients with treated stable symptomatic coronary disease to double-blind addition of nifedipine GITS  ( gastrointestinal therapeutic system ) 60 mg once daily and 3840 to placebo . The primary endpoint was the combination of death , acute myocardial infa rct ion , refractory angina , new overt heart failure , debilitating stroke , and peripheral revascularisation . Mean follow-up was 4.9 years ( SD 1.1 ) . Analysis was by intention to treat . FINDINGS 310 patients allocated nifedipine  died ( 1.64 per 100 patient-years ) compared with 291 people allocated placebo  ( 1.53 per 100 patient-years ; hazard ratio 1.07 [ 95 % CI 0.91 - 1.25 ] , p=0.41 ) . Primary endpoint rates were 4.60 per 100 patient-years for nifedipine and 4.75 per 100 patient-years for placebo ( 0.97 [ 0.88 - 1.07 ] , p=0.54 ) . With nifedipine , rate of death and any cardiovascular event or procedure was 9.32 per 100 patient-years versus 10.50 per 100 patient-years for placebo ( 0.89 [ 0.83 - 0.95 ] , p=0.0012 ) . The difference was mainly attributable to a reduction in the need for coronary angiography and interventions in patients assigned nifedipine , despite an increase in peripheral revascularisation . Nifedipine had no effect on the rate of myocardial infa rct ion . INTERPRETATION Addition of nifedipine GITS to conventional treatment of angina pectoris has no effect on major cardiovascular event-free survival .  Nifedipine GITS is safe and reduces the need for coronary angiography and interventions OBJECTIVES The primary objective of this study was to investigate the effects of the angiotensin-converting enzyme ( ACE ) inhibitor , ramipril , on carotid atherosclerosis in patients with coronary , cerebrovascular or peripheral vascular disease . BACKGROUND Angiotensin-converting enzyme inhibitors have been shown to reduce the risk of coronary events in various patient groups and to prevent the development of atherosclerosis in animal models . It has been hypothesized that the clinical benefits of ACE inhibitors may , therefore , be mediated by effects on atherosclerosis . METHODS Six hundred seventeen patients were r and omized in equal proportions to ramipril ( 5 - 10 mg daily ) or placebo . At baseline , two years and four years , carotid atherosclerosis was assessed by B-mode ultrasound , and left ventricular mass was assessed by M-mode echocardiography . RESULTS Blood pressure ( BP ) was reduced by a mean of 6 mm Hg systolic and 4 mm Hg diastolic in the ramipril group compared with the placebo group ( p<0.001 ) . There was no difference between groups in the changes in common carotid artery wall thickness ( p = 0.58 ) or in carotid plaque ( p = 0.93 ) . Left ventricular mass index decreased by 3.8 g/m2 ( 4 % ) in the ramipril group compared with the placebo group ( 2p = 0.04 ) . CONCLUSIONS The results provide no support for the hypothesis that reduced atherosclerosis is responsible for the beneficial effects of ACE inhibitors on major coronary events . It is more likely that the benefits are due to lower BP , reduced left ventricular mass or other factors such as reversal of endothelial dysfunction BACKGROUND Our underst and ing of the growing population of very old patients ( aged > or=80 years ) with coronary artery disease and hypertension is limited , particularly the relationship between blood pressure and adverse outcomes . METHODS This was a secondary analysis of the INternational VErapamil SR-Tr and olapril STudy ( INVEST ) , which involved 22,576 clinical ly stable hypertensive coronary artery disease patients aged > or=50 years . The patients were grouped by age in 10-year increments ( aged > or=80 , n=2180 ; 70-<80 , n=6126 ; 60-<70 , n=7602 ; < 60 , n=6668 ) . Patients were r and omized to either verapamil SR- or atenolol-based treatment strategies , and primary outcome was first occurrence of all-cause death , nonfatal myocardial infa rct ion , or nonfatal stroke . RESULTS At baseline , increasing age was associated with higher systolic blood pressure , lower diastolic blood pressure , and wider pulse pressure ( P < .001 ) . Treatment decreased systolic , diastolic , and pulse pressure for each age group . However , the very old retained the widest pulse pressure and the highest proportion ( 23.6 % ) with primary outcome . The adjusted hazard ratio for primary outcomes showed a J-shaped relationship among each age group with on-treatment systolic and diastolic pressures . The systolic pressure at the hazard ratio nadir increased with increasing age , highest for the very old ( 140 mm Hg ) . However , diastolic pressure at the hazard ratio nadir was only somewhat lower for the very old ( 70 mm Hg ) . Results were independent of treatment strategy . CONCLUSION Optimal management of hypertension in very old coronary artery disease patients may involve targeting specific systolic and diastolic blood pressures that are higher and somewhat lower , respectively , compared with other age groups BACKGROUND Treatment with angiotensin-converting-enzyme ( ACE ) inhibitors reduces the rate of cardiovascular events among patients with left-ventricular dysfunction and those at high risk of such events . We assessed whether the ACE inhibitor perindopril reduced cardiovascular risk in a low-risk population with stable coronary heart disease and no apparent heart failure . METHODS We recruited patients from October , 1997 , to June , 2000 . 13655 patients were registered with previous myocardial infa rct ion ( 64 % ) , angiographic evidence of coronary artery disease ( 61 % ) , coronary revascularisation ( 55 % ) , or a positive stress test only ( 5 % ) . After a run-in period of 4 weeks , in which all patients received perindopril , 12218 patients were r and omly assigned perindopril 8 mg once daily ( n=6110 ) , or matching placebo ( n=6108 ) . The mean follow-up was 4.2 years , and the primary endpoint was cardiovascular death , myocardial infa rct ion , or cardiac arrest . Analysis was by intention to treat . FINDINGS Mean age of patients was 60 years ( SD 9 ) , 85 % were male , 92 % were taking platelet inhibitors , 62 % beta blockers , and 58 % lipid-lowering therapy . 603 ( 10 % ) placebo and 488 ( 8 % ) perindopril patients experienced the primary endpoint , which yields a 20 % relative risk reduction ( 95 % CI 9 - 29 , p=0.0003 ) with perindopril . These benefits were consistent in all predefined subgroups and secondary endpoints . Perindopril was well tolerated . INTERPRETATION Among patients with stable coronary heart disease without apparent heart failure , perindopril can significantly improve outcome . About 50 patients need to be treated for a period of 4 years to prevent one major cardiovascular event . Treatment with perindopril , on top of other preventive medications , should be considered in all patients with coronary heart disease BACKGROUND Angiotensin-converting-enzyme ( ACE ) inhibitors are effective in reducing the risk of heart failure , myocardial infa rct ion , and death from cardiovascular causes in patients with left ventricular systolic dysfunction or heart failure . ACE inhibitors have also been shown to reduce atherosclerotic complications in patients who have vascular disease without heart failure . METHODS In the Prevention of Events with Angiotensin Converting Enzyme Inhibition ( PEACE ) Trial , we tested the hypothesis that patients with stable coronary artery disease and normal or slightly reduced left ventricular function derive therapeutic benefit from the addition of ACE inhibitors to modern conventional therapy . The trial was a double-blind , placebo-controlled study in which 8290 patients were r and omly assigned to receive either  tr and olapril  at a target dose of  4 mg  per  day ( 4158 patients ) or matching placebo ( 4132 patients ) . RESULTS The mean ( + /-SD ) age of the patients was 64+/-8 years , the mean blood pressure 133+/-17/78+/-10 mm Hg , and the mean left ventricular ejection fraction 58+/-9 percent . The patients received intensive treatment , with 72 percent having previously undergone coronary revascularization and 70 percent receiving lipid-lowering drugs . The incidence of the primary end point -- death from cardiovascular causes , myocardial infa rct ion , or coronary revascularization -- was 21.9 percent in the tr and olapril group , as compared with 22.5 percent in the placebo group ( hazard ratio in the tr and olapril group , 0.96 ; 95 percent confidence interval , 0.88 to 1.06 ; P=0.43 ) over a median follow-up period of 4.8 years . CONCLUSIONS In patients with stable coronary heart disease and preserved left ventricular function who are receiving " current st and ard " therapy and in whom the rate of cardiovascular events is lower than in previous trials of ACE inhibitors in patients with vascular disease , there is no evidence that the addition of an ACE inhibitor provides further benefit in terms of death from cardiovascular causes , myocardial infa rct ion , or coronary revascularization 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: These results suggest that reducing DBP to 80 mmHg or less would significantly reduce coronary revascularization and heart failure but at the expense of causing hypotension in CAD patients .
background: The target of diastolic blood pressure ( DBP ) remains controversial in patients with coronary artery disease ( CAD ) .