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Review
. 2011 Apr 26:342:d2234.
doi: 10.1136/bmj.d2234.

Angiotensin receptor blockers and risk of myocardial infarction: meta-analyses and trial sequential analyses of 147 020 patients from randomised trials

Sripal Bangalore  1 , Sunil Kumar, Jørn Wetterslev, Franz H Messerli
Affiliations
Review

Angiotensin receptor blockers and risk of myocardial infarction: meta-analyses and trial sequential analyses of 147 020 patients from randomised trials

Sripal Bangalore et al. BMJ. .

Abstract

Objectives: To evaluate the cardiovascular outcomes and other outcomes associated with angiotensin receptor blockers.

Design: Systematic review of randomised controlled trials with meta-analysis and trial sequential analysis (TSA).

Data sources and study selection: Pubmed, Embase, and CENTRAL searches for randomised clinical trials, until August 2010, of angiotensin receptor blockers compared with controls (placebo/active treatment) that enrolled at least 100 participants and had a follow-up of at least one year.

Data extraction: Myocardial infarction, death, cardiovascular death, angina pectoris, stroke, heart failure, and new onset diabetes.

Results: 37 randomised clinical trials included 147,020 participants and had a total follow-up of 485,166 patient years. When compared with controls (placebo/active treatment), placebo, or active treatment, angiotensin receptor blockers were not associated with an increase in the risk of myocardial infarction (relative risk 0.99, 95% confidence interval 0.92 to 1.07), death, cardiovascular death, or angina pectoris. Compared with controls, angiotensin receptor blockers were associated with a reduction in the risk of stroke (0.90, 0.84 to 0.98), heart failure (0.87, 0.81 to 0.93), and new onset diabetes (0.85, 0.78 to 0.93), with similar results when compared with placebo or with active treatment. Based on trial sequential analysis, there is no evidence even for an average 5.0-7.5% (upper confidence interval 5-11%) relative increase in myocardial infarction (absolute increase of 0.3%), death, or cardiovascular death with firm evidence for relative risk reduction of stroke (at least 1%, average 10%) (compared with placebo only), heart failure (at least 5%, average 10%), and new onset diabetes (at least 4%, average 10%) with angiotensin receptor blockers compared with controls.

Conclusions: This large and comprehensive analysis produced firm evidence to refute the hypothesis that angiotensin receptor blockers increase the risk of myocardial infarction (ruling out even a 0.3% absolute increase). Compared with controls, angiotensin receptor blockers reduce the risk of stroke, heart failure, and new onset diabetes.

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Conflict of interest statement

Competing interests: All authors have completed the Unified Competing Interest form at www.icmje.org/coi_disclosure.pdf (available available on request from the corresponding author) and declare: no support from any organisation for the submitted work; FHM has been an occasional consultant/speaker for Novartis, Daiichi Sankyo, Sanofi, and Savient Pharmaceuticals and has received grants from Novartis, Forest, and Boehringer Ingelheim; no other relationships or activities that could appear to have influenced the submitted work.

Figures

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Fig 1 Study identification, selection, and exclusions
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Fig 2 Angiotensin receptor blockers (ARBs) and myocardial infarction, stratified by comparison group (placebo v active treatment)
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Fig 3 Angiotensin receptor blockers (ARBs) and all cause mortality, stratified by comparison group (placebo v active treatment)
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Fig 4 Angiotensin receptor blockers (ARBs) and cardiovascular mortality, stratified by comparison group (placebo v active treatment)
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Fig 5 Angiotensin receptor blockers (ARBs) and angina pectoris, stratified by comparison group (placebo v active treatment)
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Fig 6 Angiotensin receptor blockers (ARBs) (ARBs) and stroke, stratified by comparison group (placebo v active treatment)
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Fig 7 Angiotensin receptor blockers (ARBs) and heart failure, stratified by comparison group (placebo v active treatment)
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Fig 8 Angiotensin receptor blockers (ARBs) and new onset diabetes mellitus, stratified by comparison group (placebo v active treatment)
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