This generally well-conducted review assessed angiotensin-converting enzyme (ACE) inhibitors in patients with coronary heart disease and absence of heart failure or left ventricular systolic dysfunction. The authors concluded that ACE inhibitor therapy significantly reduced mortality and major cardiovascular events compared with placebo. This conclusion was likely to be reliable.

To assess whether long-term medication with angiotensin-converting enzyme (ACE) inhibitors decreases major cardiovascular events and mortality in patients with coronary artery disease and absence of heart failure or left ventricular systolic dysfunction.

EMBASE, International Pharmaceutical Abstracts and Cochrane Controlled Trials Register were searched from inception to 2004. MEDLINE was searched from 1990 to 2004. Search terms were reported. The reference lists of relevant publications were also screened. National and international colleagues were contacted for relevant studies. Conference proceedings of the American Heart Association, American College of Cardiology and European Society of Cardiology were searched for 2003 and 2004.

Randomised controlled trials (RCTs) that compared ACE inhibitors to a placebo, with a follow-up of 2 years or longer, in patients with stable coronary artery disease and either no signs/symptoms of heart failure or no documented left ventricular dysfunction were eligible for inclusion. The primary review outcomes were all-cause mortality, cardiovascular death and myocardial infarction (MI). Additional outcomes were stroke, cardiac arrest, myocardial revascularisation, hospitalisation because of unstable angina and heart failure, and onset of diabetes mellitus.

Included studies assessed five ACE inhibitors: ramipril, quinapril hydrochloride, enalapril maleate, perindopril and Trandolapril. Studies included patients with either documented coronary artery disease or a high proportion with coronary artery disease or other forms of atherosclerotic disease or high risk of cardiovascular disease.

The authors stated neither how the papers were selected for the review nor how many reviewers performed the selection.

The quality of studies was assessed using the following criteria: adequacy of allocation concealment; blindness of patients and physicians to the treatment; and blinded assessment.

Two reviewers independently performed the validity assessment. The authors did not state how disagreements were resolved.

It appeared that the authors extracted the data on the point estimates for: all-cause mortality; cardiovascular death; MI; stroke; cardiac arrest; hospitalisation because of unstable angina; myocardial revascularisation; hospitalisation because of heart failure; and onset of diabetes mellitus. Intention-to-treat data were extracted where possible. It appeared that the authors estimated odds ratios (ORs) with 95% confidence intervals (CIs).

The authors stated neither how the data were extracted for the review nor how many reviewers performed the data extraction.

The studies were combined in meta-analyses using a fixed-effect model. Pooled ORs with 95% CIs were calculated. The studies were weighted using the inverse variance method. Statistical heterogeneity was investigated using Chi² statistics. Sensitivity analyses using a number of alternative analyses were conducted. Publication bias was visualised using funnel plots and assessed using the method of Begg and Mazumdar.

Seven RCTs (n= 33,960) were included in the meta-analysis. The sample size varied from 460 to 12,218. All studies were scored 5 using the measures of quality assessment. The mean follow-up duration of included studies was 4.4 years (range 2 to 5 years).

When the studies were pooled, ACE inhibitors were significantly associated with a reduction in all-cause mortality compared with control group (OR 0.86, 95% confidence interval, CI: 0.79, 0.93, p<0.001; seven RCTs), a reduction in cardiovascular death (OR: 0.81, 95% CI: 0.73, 0.90, p<0.001; seven RCTs), a reduction in MI (OR 0.82, 95% CI: 0.75, 0.89, p<0.001; seven RCTs), and a reduction in the occurrence of stroke (OR 0.77, 95% CI: 0.66, 0.88, p<0.001; seven RCTs).

Results for the secondary outcomes of the reduction of hospitalisation because of heart failure, myocardial revascularisation and new onset of diabetes mellitus were also reported.

There was no evidence of statistically significant heterogeneity for the outcome measures. Sensitivity analyses did not materially affect the results. No evidence of publication bias was found according to the visual scanning of funnel plots and the test of Begg and Mazumdar.

ACE inhibitor medications were associated with a reduction in all-cause mortality and major cardiovascular events in patients without heart failure or left ventricular systolic dysfunction.

This review's inclusion criteria were clear. Several relevant databases were searched. Efforts were made to find published and unpublished studies to minimise the potential for publication bias. Publication bias was evaluated and little evidence of it was found, but funnel plots were not presented in the report. The authors did not state whether language restrictions were applied in the search, which made it difficult to assess the risk of language bias. Steps were taken to minimise bias by having more than one reviewer undertake the validity assessment, but it was unclear whether the processes of study selection and data extraction were also performed in duplicate. Adequate details of the primary studies were provided. Relevant criteria were used to examine the study quality. Statistical heterogeneity was assessed and appropriate statistical methods were used to pool the results. This review was generally well conducted. The authors' conclusions reflected the evidence presented and were likely to be reliable.

Practice: The authors stated that ACE inhibitor therapy should be systematically used in all patients with documented coronary artery disease.

Research: The authors did not state any implications for research.

No external funding. A number of financial relationships with pharmaceutical companies were disclosed.

This is a critical abstract of a systematic review that meets the criteria for inclusion on DARE. Each critical abstract contains a brief summary of the review methods, results and conclusions followed by a detailed critical assessment on the reliability of the review and the conclusions drawn.