Angiotensin-Converting Enzyme Inhibitors or Angiotensin Receptor Blockers Are Beneficial in Normotensive Atherosclerotic Patients: A Collaborative Meta-Analysis of Randomized Trials

Study Questions:

Are angiotensin-converting enzyme inhibitors (ACE-Is) or angiotensin-receptor blockers (ARBs) beneficial in individuals with, or at increased risk for, atherosclerotic vascular disease who are normotensive?


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-Is or ARBs, which enrolled at least 1,000 patients with, or at increased risk for, atherosclerotic vascular disease, and followed them for at least 12 months. All eligible trials were approached to obtain data stratified by baseline systolic pressures.


Pooled data included 13 trials of 80,594 patients; outcomes included 9,043 all-cause deaths, 5,674 cardiovascular deaths, 3,106 myocardial infarctions, and 4,452 strokes. ACE-Is or ARBs reduced the composite primary outcome of cardiovascular death, nonfatal myocardial infarction, or nonfatal 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 mm Hg, ACE-Is or ARBs 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 (odds ratio [OR], 0.81; 95% confidence interval [CI], 0.75-0.88) and those without diabetes (OR, 0.79; 95% CI, 0.70-0.89).


The authors concluded that ACE-Is or ARBs are beneficial in patients with, or at increased risk for, atherosclerotic disease even if their systolic pressure is <130 mm Hg before treatment.


The findings support treating patients with coronary artery disease or diabetes with an ACE-I or ARB when blood pressure is <130 mm Hg. Since this analysis focused on placebo-controlled trials, we do not know if it is blood pressure lowering within the 115-140 mm Hg range or the renin-angiotensin-aldosterone system blockade effect. Also, the suggestion is in conflict with the ACCORD study and the analysis of ONTARGET, in which lowering the blood pressure to <130 mm Hg is no better than 140 mm Hg. Nonetheless, the sum of the evidence suggests there is no need to ‘back off’ if patients are tolerating lower blood pressure levels without side effects.

Clinical Topics: Heart Failure and Cardiomyopathies, Prevention, Atherosclerotic Disease (CAD/PAD), Acute Heart Failure, Hypertension

Keywords: Odds Ratio, Angiotensin Receptor Antagonists, Coronary Artery Disease, Stroke, Myocardial Infarction, Atherosclerosis, Renin-Angiotensin System, Systole, Cause of Death, Heart Failure, Cardiovascular Diseases, Confidence Intervals, Hypertension, Diabetes Mellitus, MEDLINE

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