Physicians' Academy for Cardiovascular Education

ACE Inhibitors or ARB's are beneficial in normotensive atherosclerotic patients

Literature - McAlister FA, et al , Eur Heart J. 2011 Oct 31

Angiotensin-converting enzyme inhibitors or angiotensin receptor blockers are beneficial in normotensive atherosclerotic patients: a collaborative meta-analysis of randomized trials.

McAlister FA; for the Renin Angiotensin System Modulator Meta-Analysis Investigators.
Eur Heart J. 2011 Oct 31. [Epub ahead of print]


It is unclear whether angiotensin-converting enzyme inhibitors (ACE-I) or angiotensin receptor blockers (ARB) are beneficial in individuals with, or at increased risk for, atherosclerotic vascular disease who are normotensive.

Methods and results

Two investigators independently searched MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials from 1980 to 2011, bibliographies, and contacted primary study authors for randomized placebo-controlled outcome trials evaluating ACE-I or ARB which enrolled at least 1000 patients with, or at increased risk for, atherosclerotic vascular disease and followed them for at least 12 months. We approached all eligible trials to obtain data stratified by baseline systolic pressures. We pooled data from 13 trials of 80 594 patients; outcomes included 9043 all-cause deaths, 5674 cardiovascular deaths, 3106 myocardial infarctions, and 4452 strokes. Angiotensin-converting enzyme inhibitors or ARB reduced the composite primary outcome of cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke by 11% (95% confidence interval 7-15%), with no variation in efficacy across baseline systolic blood pressure strata. In patients with baseline systolic pressure <130 mmHg, ACE-I or ARB reduced the composite primary outcome by 16% (10-23%) and all-cause mortality by 11% (4-18%)-this benefit was consistent across all subgroups examined including those without systolic heart failure (OR: 0.81, 95% CI: 0.75-0.88) and those without diabetes (OR: 0.79, 95% CI: 0.70-0.89).


Angiotensin-converting enzyme inhibitors or ARB are beneficial in patients with, or at increased risk for, atherosclerotic disease even if their systolic pressure is <130 mmHg before treatment.


Although many guidelines endorse the cardioprotective effects of ACE inhibitors (ACE-I) and ARBs in patients with or at increased risk of atherosclerosis, there is a discrepancy between the guidelines as to whether these drugs should be prescribed to people with normal blood pressure (SBP <130 mmHg) [1,2]. Although several studies with ACE-I and ARBs showed that the cardiovascular effects were similar whether or not patients had hypertension at baseline, the definition of hypertension varied by study and sometimes different types of drugs, including combinations, were compared [3-7]. Therefore the question whether ACE-I or ARB are beneficial in individuals with or at risk of, atherosclerotic disease who have normal SBP (<130 mm Hg) remains unanswered. This study attempted to answer this question.

Main results

There were 13 studies included with information on 80,594 patients. 9043 results include deaths from all causes and 11,005 cases of the primary composite outcome of cardiovascular death, nonfatal myocardial infarction or nonfatal stroke.
The relative benefits of ACE-I or ARBs on the primary composite outcome did not differ between blood pressure strata. Meta-regression analysis on all 80,954 patients showed that age, baseline SBP, degree of systolic blood pressure reduction during the study, and duration of the study were not significantly associated with the magnitude of the effect on the primary outcome with ACE-I or ARBs. Outcome-specific analysis confirmed the benefits of ACE-I and ARBs for each part of the primary outcome and for death from all causes. Although the magnitude of the effects for some outcomes differed between baseline SBP strata, the benefits were generally greater in patients with SBP <130 mmHg at baseline, the inter-trial heterogeneity in these patients was the smallest. The benefits were consistent across subgroups defined a priori, including patients without systolic heart failure or diabetes.


ACE-I and ARBs are effective in preventing cardiovascular events and mortality in normotensive high-risk patients. The prescription of these drugs should therefore be based on the cardiovascular risk of a patient and not just on his blood pressure.


1. Graham I, Atar D, et al. European guidelines on cardiovascular disease prevention in clinical practice. Fourth Joint Task Force of the European Society of Cardiology and other societies on Cardiovascular Disease Prevention in Clinical Practice. Eur Heart J 2007;28:2375–2414.
2. Chobanian AV, Bakris GL, et al.The Seventh Report of the Joint National Commission on prevention, detection, evaluation, and treatment of high blood pressure. The JNC 7 Report. JAMA 2003;289:2560–2572.
3. Sleight P, Yusuf S, Pogue J, Tsuyuki R, Diaz R, Probstfield J. Blood-pressure reduction and cardiovascular risk in HOPE study. Lancet 2001;358:2130–2131.
4. Anand IS, Rector TS, et al. Effect of baseline and changes in systolic blood pressure over time on the effectiveness of valsartan in the Valsartan Heart Failure Trial. Circ Heart Fail 2008;1:34–42.
5. Remme WJ, Deckers JW, et al. Secondary prevention of coronary disease with ACE Inhibition—does blood pressure reduction with perindopril explain the benefits in EUROPA? Cardiovasc Drugs Ther 2009;23:161–170.
6. Brugts JJ, Ninomiya T, et al. The consistency of the treatment effect of an ACE-inhibitor based treatment regimen in patients with vascular disease or high risk of vascular disease: a combined analysis of individual data of ADVANCE, EUROPA, and PROGRESS trials. Eur Heart J 2009;30:1385–1394.
7. Thompson AM, Hu T, et al. Antihypertensive treatment and secondary prevention of cardiovascular disease events among persons without hypertension. A meta-analysis. JAMA 2011;305:913–922.

Share this page with your colleagues and friends: