Postconditioning in ST-elevation myocardial infarction: a systematic review, critical appraisal, and meta-analysis of randomized clinical trials

M Abdelnoor,1,2 I Sandven,1 S Limalanathan,3 J Eritsland3 1Centre of Epidemiology and Biostatistics, 2Centre of Clinical Heart Research, 3Department of Cardiology, Oslo University Hospital, Ullevål, NorwayObjective: We aimed to summarize the evidence from randomized clinical trials studies examining the efficacy of ischemic postconditioning (IPost) in ST-elevation myocardial infarction. Design: The study was a systematic review and critical appraisal, with meta-analysis of randomized clinical trials. Materials and methods: We searched the literature. A total of 21 randomized clinical trials were identified. Both fixed effect and random effects models were used to synthesize the results of individual studies. Heterogeneity between studies was examined by subgroup and random effects meta-regression analyses, considering ptient-related and study-level variables. Publication bias, or “small-study effect”, was evaluated. Results: Substantial heterogeneity was present. The random effects model pooled estimate for the outcome infarct size assessed by cardiac magnetic resonance was estimated by the standardized mean difference (SMD) =−0.06, 95% confidence interval (CI): −0.34 to 0.21, ie, no effect of IPost. For the end point infarct size, estimated by biomarkers of myocardial necrosis, an overall pooled effect was SMD =−0.58, 95% CI: −0.96 to −0.19. This effect disappeared in powered and nonbiased studies (SMD =0.03, 95% CI: −0.48 to 0.55). Finally, for the outcome left ventricular ejection fraction, SMD =0.47 95% CI: 0.20 to 0.74. Unfortunately, selection bias (small-study effect) was present. For this outcome, the meta-regression showed that both presence of hypertension and the inclusion of nonbiased studies explained 28.3% of the heterogeneity among the studies. Simulation by the “trim and fill” method, which controlled for selection bias using random effects model, diluted the effect (SMD =0.17 95% CI: −0.13 to 0.48). No effects by IPost on ST-segment resolution or on the majority of adverse clinical events were observed during follow up, except the incidence of congestive heart failure was found. Conclusion: Evidence from this study suggests no cardioprotection from IPost, on surrogate and the majority of clinical end points. A possible beneficial effect on the incidence of congestive heart failure needs to be replicated by a large clinical trial. Keywords: ischemic postconditioning, acute myocardial infarction, percutaneous coronary interventio