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Review
. 2017 Jan 19:356:j4.
doi: 10.1136/bmj.j4.

Renin angiotensin system inhibitors for patients with stable coronary artery disease without heart failure: systematic review and meta-analysis of randomized trials

Sripal Bangalore  1 , Robert Fakheri  2 , Simon Wandel  3 , Bora Toklu  4 , Jasmin Wandel  5 , Franz H Messerli  6   7   8
Affiliations
Review

Renin angiotensin system inhibitors for patients with stable coronary artery disease without heart failure: systematic review and meta-analysis of randomized trials

Sripal Bangalore et al. BMJ. .

Abstract

Objective: To critically evaluate the efficacy of renin angiotensin system inhibitors (RASi) in patients with coronary artery disease without heart failure, compared with active controls or placebo.

Design: Meta-analysis of randomized trials.

Data sources: PubMed, EMBASE, and CENTRAL databases until 1 May 2016.

Eligibility criteria for selecting studies: Randomized trials of RASi versus placebo or active controls in patients with stable coronary artery disease without heart failure (defined as left ventricular ejection fraction ≥40% or without clinical heart failure). Each trial had to enroll at least 100 patients with coronary artery disease without heart failure, with at least one year's follow-up. Studies were excluded if they were redacted or compared use of angiotensin converting enzyme inhibitors with angiotensin receptor blockers. Outcomes were death, cardiovascular death, myocardial infarction, angina, stroke, heart failure, revascularization, incident diabetes, and drug withdrawal due to adverse effects.

Results: 24 trials with 198 275 patient years of follow-up were included. RASi reduced the risk of all cause mortality (rate ratio 0.84, 95% confidence interval 0.72 to 0.98), cardiovascular mortality (0.74, 0.59 to 0.94), myocardial infarction (0.82, 0.76 to 0.88), stroke (0.79, 0.70 to 0.89), angina, heart failure, and revascularization when compared with placebo but not when compared with active controls (all cause mortality, 1.05, 0.94 to 1.17; Pinteraction=0.006; cardiovascular mortality, 1.08, 0.93 to 1.25, Pinteraction<0.001; myocardial infarction, 0.99, 0.87 to 1.12, Pinteraction=0.01; stroke, 1.10, 0.93 to 1.31; Pinteraction=0.002). Bayesian meta-regression analysis showed that the effect of RASi when compared with placebo on all cause mortality and cardiovascular mortality was dependent on the control event rate, such that RASi was only beneficial in trials with high control event rates (>14.10 deaths and >7.65 cardiovascular deaths per 1000 patient years) but not in those with low control event rates.

Conclusions: In patients with stable coronary artery disease without heart failure, RASi reduced cardiovascular events and death only when compared with placebo but not when compared with active controls. Even among placebo controlled trials in this study, the benefit of RASi was mainly seen in trials with higher control event rates but not in those with lower control event rates. Evidence does not support a preferred status of RASi over other active controls.

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Conflict of interest statement

All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare: no support from any organisation for the submitted work; SB declares honorariums from Daiichi-Sankyo, Pfizer, Abbott, Merck, Boerhinger-Ingelheim, Gilead, and Abbott-Vascular; SW is employed and hold shares at Novartis Pharma AG (Basel, Switzerland); FHM declares honorariums from Daiichi-Sankyo, Pfizer, Abbott, Servier, WebMD, Ipca, American College of Cardiology, Menarini, and Relypsa; the remaining authors have no relevant disclosures; none of the authors received any compensation for their work on this manuscript.

Figures

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Fig 1 Forest plot showing effect of renin angiotensin system inhibitors (RASi) versus placebo or active controls on all cause mortality in patients with stable coronary artery disease without heart failure. D+L=DerSimonian and Laird; I-V=inverse variance; CHD=coronary heart disease
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Fig 2 Bayesian meta-regression analysis of the influence of baseline risk (control event rate) on the effect size of RASi versus placebo on all cause mortality
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Fig 3 Forest plot showing effect of renin angiotensin system inhibitors (RASi) versus placebo or active controls on cardiovascular mortality in patients with stable coronary artery disease without heart failure. D+L=DerSimonian and Laird; I-V=inverse variance; CHD=coronary heart disease
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Fig 4 Bayesian meta-regression analysis of the influence of baseline risk (control event rate) on the effect size of RASi versus placebo on cardiovascular mortality
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Fig 5 Forest plot showing effect of renin angiotensin system inhibitors (RASi) versus placebo or active controls on myocardial infarction in patients with stable coronary artery disease without heart failure. D+L=DerSimonian and Laird; I-V=inverse variance; CHD=coronary heart disease
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Fig 6 Bayesian meta-regression analysis of the influence of baseline risk (control event rate) on the effect size of RASi versus placebo on myocardial infarction
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Fig 7 Forest plot showing effect of of renin angiotensin system inhibitors (RASi) versus placebo or active controls on stroke in patients with stable coronary artery disease without heart failure. CHD=coronary heart disease
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Fig 8 Forest plot showing effect of renin angiotensin system inhibitors (RASi) versus placebo or active controls on angina pectoris in patients with stable coronary artery disease without heart failure. CHD=coronary heart disease
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Fig 9 Forest plot showing effect of renin angiotensin system inhibitors (RASi) versus placebo or active controls on heart failure in patients with stable coronary artery disease without heart failure on trial entry
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References

    1. Yusuf S, Sleight P, Pogue J, Bosch J, Davies R, Dagenais G. The Heart Outcomes Prevention Evaluation Study Investigators. Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. N Engl J Med 2000;342:145-53. 10.1056/NEJM200001203420301 pmid:10639539. - DOI - PubMed
    1. Fox KM. EURopean trial On reduction of cardiac events with Perindopril in stable coronary Artery disease Investigators. 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). Lancet 2003;362:782-8. 10.1016/S0140-6736(03)14286-9 pmid:13678872. - DOI - PubMed
    1. Yusuf S, Lonn E.Anti-ischaemic effects of ACE inhibitors: review of current clinical evidence and ongoing clinical trials. Eur Heart J 1998;19 (Suppl J):J36-44. - PubMed
    1. Braunwald E, Domanski MJ, Fowler SE, et al. PEACE Trial Investigators. Angiotensin-converting-enzyme inhibition in stable coronary artery disease. N Engl J Med 2004;351:2058-68. 10.1056/NEJMoa042739 pmid:15531767. - DOI - PMC - PubMed
    1. Pitt B, O’Neill B, Feldman R, et al. QUIET Study Group. The QUinapril Ischemic Event Trial (QUIET): evaluation of chronic ACE inhibitor therapy in patients with ischemic heart disease and preserved left ventricular function. Am J Cardiol 2001;87:1058-63. 10.1016/S0002-9149(01)01461-8 pmid:11348602. - DOI - PubMed

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