Abstract
Previous experimental and clinical trials suggest that cyclosporine A (CsA) reduces myocardial ischemia-reperfusion injury (IRI) but its clinical benefits are uncertain. To assess CsA effect on IRI evaluated by cardiac biomarkers. Pubmed, Cochrane, Web of Science and Embase databases were screened for randomized controlled trials assessing at least one cardiac biomarker and comparing CsA to placebo in situations at risk of IRI: acute myocardial infarction (AMI), cardiac surgery and successfully resuscitated cardiac arrest. Main outcome was troponin, creatine kinase (CK) and CK MB fraction (CK-MB) peak and area under the curve (AUC). Secondary outcomes were ST-segment resolution, left ventricular ejection fraction (LVEF), left ventricular end-diastolic volume (LVEDV) and major adverse cardiovascular events (MACE). Risk ratios (RR) for dichotomous data and standard mean differences (SMD) for continuous data were reported with their 95% confidence intervals (CI). Heterogeneity was assessed by sub-group and sensitivity analysis. Six trials were selected totalling 1677 patients with AMI and elective cardiac surgery receiving an intra-venous bolus of CsA or placebo at the time of reperfusion. CsA did not reduce troponin (SMD −0.44, 95% CI [−0.93, 0.05]; P = 0.08) and CK (SMD −0.75, 95% CI [−2.41, 0.91]; P = 0.37) AUC nor troponin (SMD −0.30, 95% CI [−0.72,0.13]; P = 0.17), CK (SMD −0.09, 95% CI [−0.37, 0.20]; P = 0.56) and CK-MB (SMD −0.20, 95% CI [−0.50, 0.09]; P = 0.18) peak in random-effect model (REM), with high heterogeneity. CsA was not associated with significant ST-segment resolution, LVEF improvement or MACE reduction but was associated with an increased LVEDV (SMD 0.13, 95% CI [0.01, 0.25]; P = 0.03) assessed by echography in studies of 100 patients or more, using a REM, with no heterogeneity. Results suggest no benefit from CsA to reduce IRI and potential long-term adverse left ventricular remodelling.
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