BACKGROUND: Infarct size (IS) is a major determinant of patient outcome after acute ST-segment elevation myocardial infarction (STEMI). Interventions aimed at reducing reperfusion injury, such as cardiac ischaemic postconditioning (IPost), may reduce IS and improve clinical outcomes. IPost has been shown to be feasible in patients with STEMI treated by primary percutaneous coronary intervention (PPCI). AIMS: To provide an updated summary of the efficacy of IPost, assessed by analysing accurate surrogate markers of IS. METHODS: We performed a meta-analysis of randomized controlled trials that evaluated the efficacy of IPost in STEMI patients undergoing PPCI. The main outcome was area under the curve of serum creatine kinase release (CK-AUC). Secondary outcomes were other surrogate biomarkers of IS, complete ST-segment resolution, direct measurement of IS by single-photon emission computed tomography and estimation of IS by cardiac magnetic resonance (CMR-IS). RESULTS: Eleven studies were retrieved, including 1313 STEMI patients undergoing PPCI with or without IPost. Compared with controls, we observed a significant reduction in CK-AUC (standard mean difference [SMD] -2.84 IU/L, 95% CI -5.43 to -0.25 IU/L; P=0.03). Other surrogate markers, such as CMR-IS (SMD -0.36, 95% CI -0.88 to 0.15; P=0.16), showed a non-significant IS reduction in the IPost group. CONCLUSIONS: This meta-analysis, dealing with accurate surrogate markers of IS, suggests that IPost reduces IS. However, results should be interpreted cautiously because of limited sample sizes and significant heterogeneity. Whether this translates into improvements in cardiac function and patient prognosis still needs to be demonstrated in larger prospective randomized controlled studies that are powered sufficiently.
The protective effect of ischaemic postconditioning (short cycles of reperfusion and reocclusion of a previously occluded vessel) was identified over a decade ago commanding intense interest as an approach for modifying reperfusion injury which contributes to infarct size in acute myocardial infarction. Elucidation of the major mechanisms of postconditioning has identified potential pharmacological targets for limitation of reperfusion injury. These include ligands for membrane-associated receptors, activators of phosphokinase survival signalling pathways and inhibitors of the mitochondrial permeability transition pore. In experimental models, numerous agents that target these mechanisms have shown promise as postconditioning mimetics. Nevertheless, clinical studies of ischaemic postconditioning and pharmacological postcondition in gmimetics are equivocal. The majority of experimental research is conducted in animal models which do not fully portray the complexity of risk factors and comorbidities with which patients present and which we now know modify the signalling pathways recruited in postconditioning. Cohort size and power, patient selection, and deficiencies in clinical infarct size estimation may all represent major obstacles to assessing the therapeutic efficacy of postconditioning. Furthermore, chronic treatment of these patients with drugs like ACE inhibitors, statins and nitrates may modify signalling, inhibiting the protective effect of postconditioning mimetics, or conversely induce a maximally protected state wherein no further benefit can be demonstrated. Arguably, successful translation of postconditioning cannot occur until all of these issues are addressed, that is, experimental investigation requires more complex models that better reflect the clinical setting, while clinical investigation requires bigger trials with appropriate patient selection and standardization of clinical infarct size measurements.