Pioglitazone for Secondary Stroke Prevention: A Systematic Review and Meta-Analysis

Background and Purpose Pioglitazone reduced major vascular events after ischemic stroke in a recent randomized controlled trial. The purpose of this study was to conduct a meta-analysis of randomized controlled trials to evaluate the effect of pioglitazone therapy in reducing the risk of recurrent stroke in stroke patients. Methods Pubmed, EMBASE, Medline, and Cochrane Central Register of Controlled Trials from 1966 to March 2016 were searched to identify relevant studies. We included randomized controlled trials that included comparison of pioglitazone versus control and trials in which quantitative estimates of the hazard ratio and 95% confidence interval for recurrent stroke associated with pioglitazone therapy among stroke patients were reported. Hazard ratios with 95% confidence intervals were used as a measure of the association between use of pioglitazone and risks of recurrent stroke (ischemic and hemorrhagic) and major vascular events (nonfatal stroke, nonfatal myocardial infarction, and cardiovascular death) after pooling data across trials. Between-study heterogeneity was assessed using the I-2 statistic. Results Three randomized controlled trials with 4980 participants were identified. Use of pioglitazone in stroke patients with insulin resistance, prediabetes, and diabetes mellitus was associated with lower risk of recurrent stroke (hazard ratio 0.68; 95% confidence interval, 0.50-0.92; P=0.01) and future major vascular events (hazard ratio 0.75; 95% confidence interval, 0.64-0.87; P=0.0001). There was no heterogeneity across trials. There was no evidence of an effect on all-cause mortality and heart failure. Conclusions Pioglitazone reduces recurrent stroke and major vascular events in ischemic stroke patients with insulin resistance, prediabetes, and diabetes mellitus.