Vibhuti Singh, MD, MPH
Do angiotensin-converting enzyme inhibitors (ACE-Is) or angiotensin-receptor blockers (ARBs) reduce adverse cardiovascular (CV) outcomes in normotensive patients with or at risk for atherosclerotic vascular disease?
Included studies compared ACE-Is or ARBs given for ≥ 12 months with placebo in patients who had, or were at increased risk for, atherosclerotic vascular disease; enrolled ≥ 1000 patients; and prospectively assessed CV outcomes. Exclusion criteria were use of initial combination therapy or > 1 renin–angiotensin system modulator, and trials done exclusively in patients with hypertension. Outcomes were a composite of CV endpoints (first event of CV mortality, nonfatal myocardial infarction [MI], and nonfatal stroke), CV mortality, MI, stroke, and all-cause mortality.
MEDLINE, EMBASE/Excerpta Medica, Cochrane Central Register of Controlled Trials (all 1980 to Mar 2011); and reference lists were searched for randomized controlled trials (RCTs). Authors were contacted for data stratified by baseline systolic blood pressure (SBP). 13 RCTs (n = 80 594, mean age 55 to 70 y, 41% to 91% men, mean baseline SBP 113 to 152 mm Hg) met inclusion criteria; individual patient data were obtained for 10 RCTs and data stratified by baseline SBP for the other 3 RCTs.
Meta-analysis showed that ACE-Is or ARBs reduced the composite CV endpoint and its components more than placebo; ACE-Is or ARBs had a borderline statistical benefit for all-cause mortality (Table). Results were consistent across baseline SBP levels for the composite CV endpoint, all-cause mortality, MI, and stroke. ACE-Is or ARBs reduced CV mortality in patients with baseline SBP < 130 mm Hg (relative risk reduction [RRR] 16%, 95% CI 8 to 23) but not in those with higher baseline SBP (130 to 139 mm Hg, RRR 7%, CI −6 to 17; ≥ 140 mm Hg, RRR 0%, CI −7 to 7; P = 0.02 for interaction).
Angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers reduce adverse cardiovascular outcomes in patients with, or at risk for, atherosclerosis. Results are consistent for most outcomes regardless of baseline systolic blood pressure.
ACE-Is or ARBs vs placebo in patients with, or at increased risk for, atherosclerosis*
*ACE-I = angiotensin-converting enzyme inhibitor; ARB = angiotensin-receptor blocker; CV = cardiovascular; MI = myocardial infarction; other abbreviations defined in Glossary. RRR, NNT, and CI calculated from odds ratios and control event rates reported in article using a fixed-effect model.
†Interaction across baseline systolic blood pressure levels (< 130 mm Hg, 130 to 139 mm Hg, and ≥ 140 mm Hg) for CV mortality, P = 0.02; no interaction by systolic blood pressure level for other outcomes.
‡First of CV mortality, nonfatal MI, or nonfatal stroke.
Vibhuti Singh. Review: ACE-Is or ARBs reduce adverse CV outcomes regardless of baseline systolic blood pressure. Ann Intern Med. 2012;157:JC1–8. doi: 10.7326/0003-4819-157-2-201207170-02008
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Published: Ann Intern Med. 2012;157(2):JC1-8.
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