Abstract TMP21: Cilostazol for Prevention of Cerebral Vasospasm and Cerebral Ischemia in Patients With Aneurysmal Subarachnoid Hemorrhage: A Meta-Analysis of Randomized Controlled Clinical Trials

Abstract

Introduction: Cilostazol, a selective inhibitor of phosphodiesterase 3, may reduce symptomatic vasospasm and associated cerebral ischemia and improve outcomes in patients with aneurysmal subarachnoid hemorrhage (aSAH) due to its anti-platelet, anti-proliferative, and vasodilatory effects. Due to recent publication of randomized controlled clinical trials, a meta-analysis was performed to identify the common treatment effect. Methods: We performed a meta-analysis of four randomized controlled clinical trials. The primary endpoint of interest was cerebral ischemia related to vasospasm. Secondary endpoints were angiographic vasospasm, new cerebral infarct, mortality, and death or disability at the 90 days following randomization. Using random-effects models with study as a random effect, relative risks (RR) and 95% confidence intervals (CI) were generated Results: A total of 405 subjects (200 randomized to oral cilostazol 100 mg twice per day) were included in the meta-analysis. The proportion of subjects with cerebral ischemia related to vasospasm was significantly lower in those who were assigned to cilostazol treatment (RR 0.46; 95% CI 0.21-1.00; p< 0.050) without any heterogeneity between the trials (Cochran’s Q statistic 1.52, df 2; P = .468, I 2 =0.0%). The proportion of subjects who had new cerebral infarction was significantly lower in subjects who were assigned to cilostazol treatment (RR 0.40, 95% CI 0.32-0.49, p=0.0009). There was a lower rate of death or disability at 90 days in subjects who were assigned to cilostazol treatment (RR 0.44, 95% 0.28-0.70, p=0.011) without any heterogeneity between the trials (Cochran’s Q statistics 1.49, df 3; P = .685, I 2 =0.0%). The proportion of subjects who had any adverse events was not significantly different in subjects who were assigned to cilostazol treatment (RR 1.24, 95% 0.68-2.25, p=0.26). Conclusion: The reduction in rates of cerebral ischemia related to vasospasm and death or disability at follow-up support further evaluation of oral cilostazol in patients with aSAH in a phase III large randomized clinical trial.