The most critical question when reading a meta-analysis report: Is it comparing apples with apples or apples with oranges?

OBJECTIVE While the number of meta-analyses published has increased recently, most of them have problems in the design, analysis, and/or presentation. An example of meta-analyses with a study selection bias is a meta-analysis of over 160,000 patients in 20 clinical trials, published in Eur Heart J in 2012 by van Vark, which concluded that the significant effect of renin-angiotensin-aldosterone system (RAAS) inhibition on all-cause mortality was limited to the class of angiotensin-converting enzyme inhibitors (ACEIs), whereas no mortality reduction could be demonstrated with angiotensin receptor blockers (ARBs). Here, we aimed to discuss how to select studies for a meta-analysis and to present our results of a re-analysis of the van Vark data. METHODS The data were re-analyzed in three steps: firstly, only ACEI/ARB-based studies (4 ACEI and 12 ARB studies) were included; secondly, placebo-controlled studies were excluded, and 10 studies left were analyzed; and thirdly, 2 studies that were retracted after the manuscript of van Vark had been published were excluded. The final analysis included 8 studies with ~65,000 patients (3 ACEI and 5 ARB studies). RESULTS The hazard ratios for all-cause mortality and cardiovascular mortality were 0.992 (95% CI 0.899-1.095; p=0.875) and 1.017 (0.932-1.110; p=0.703) for the ACEI versus control group and 1.007 (0.958-1.059; p=0.778) and 0.967 (0.911-1.025; p=0.258) for the ARB versus control group in the first step. The results were similar in the second and third steps. CONCLUSION The studies to be included in meta-analyses, particularly comparing ACEIs and ARBs, should be chosen carefully.