Efficacy of Cilostazol in Prevention of Delayed Cerebral Ischemia after Aneurysmal Subarachnoid Hemorrhage: A Meta-Analysis

J Stroke Cerebrovasc Dis. 2018 Nov;27(11):2979-2985. doi: 10.1016/j.jstrokecerebrovasdis.2018.06.027. Epub 2018 Aug 6.

Abstract

Objectives: Cilostazol, a selective inhibitor of phosphodiesterase 3, may reduce symptomatic vasospasm and improve outcome in patients with aneurysmal subarachnoid hemorrhage considering its anti-platelet and vasodilatory effects. We aimed to analyze the effects of cilostazol on symptomatic vasospasm and clinical outcome among patients with aneurysmal subarachnoid hemorrhage (aSAH).

Patients and methods: We searched PubMed and Embase databases to identify 1) prospective randomized trials, and 2) retrospective trials, between May 2009 and May 2017, that investigated the effect of cilostazol in patients with aneurysmal aSAH. All patients were enrolled after repair of a ruptured aneurysm by clipping or endovascular coiling within 72hours of aSAH. fixed-effect models were used to pool data. We used the I2 statistic to measure heterogeneity between trials.

Results: Five studies were included in our meta-analysis, comprised of 543 patients with aSAH (cilostazol [n=271]; placebo [n=272], mean age, 61.5years [SD, 13.1]; women, 64.0%). Overall, cilostazol was associated with a decreased risk of symptomatic vasospasm (0.31, 95% CI 0.20 to 0.48; P<0.001), cerebral infarction (0.32, 95% CI 0.20 to 0.52; P <0.001) and poor outcome (0.40, 95% CI 0.25 to 0.62; P<0.001). We observed no evidence for publication bias. Statistical heterogeneity was not present in any analysis.

Conclusion: Cilostazol is associated with a decreased risk of symptomatic vasospasm and may be clinically useful in the treatment of delayed cerebral vasospasm in patients with aSAH. Our results highlight the need for a large multi-center trial to confirm the observed association.

Keywords: Cilostazol—Aneurysmal subarachnoid hemorrhage—Vasospasm—Delayed Cerebral Ischemia..

Publication types

  • Meta-Analysis
  • Review

MeSH terms

  • Aged
  • Brain Ischemia / diagnosis
  • Brain Ischemia / etiology
  • Brain Ischemia / physiopathology
  • Brain Ischemia / prevention & control*
  • Chi-Square Distribution
  • Cilostazol / adverse effects
  • Cilostazol / therapeutic use*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Odds Ratio
  • Phosphodiesterase 3 Inhibitors / adverse effects
  • Phosphodiesterase 3 Inhibitors / therapeutic use*
  • Platelet Aggregation Inhibitors / adverse effects
  • Platelet Aggregation Inhibitors / therapeutic use*
  • Risk Factors
  • Subarachnoid Hemorrhage / complications
  • Subarachnoid Hemorrhage / diagnosis
  • Subarachnoid Hemorrhage / drug therapy*
  • Subarachnoid Hemorrhage / physiopathology
  • Treatment Outcome
  • Vasodilator Agents / adverse effects
  • Vasodilator Agents / therapeutic use*
  • Vasospasm, Intracranial / diagnosis
  • Vasospasm, Intracranial / etiology
  • Vasospasm, Intracranial / physiopathology
  • Vasospasm, Intracranial / prevention & control*

Substances

  • Phosphodiesterase 3 Inhibitors
  • Platelet Aggregation Inhibitors
  • Vasodilator Agents
  • Cilostazol