Cilostazol Mono and Combination Treatments in Ischemic Stroke: An Updated Systematic Review and Meta-Analysis

Background and Purpose— We performed a systematic review and meta-analysis to explore the efficacy and safety of cilostazol as a mono or combination (plus aspirin or clopidogrel) treatments compared to conventional single antiplatelet therapy (SAPT, mainly aspirin) for secondary stroke prevention. Methods— Randomized controlled trial studies were searched across multiple comprehensive databases (MEDLINE, EMBASE, and Cochrane) for review. The primary outcome was recurrent stroke comprising ischemic and hemorrhagic stroke. Secondary outcomes included ischemic stroke, hemorrhagic stroke, myocardial infarction, and composite outcomes. We performed an updated systematic review and meta-analysis of the identified reports, including 2 recently published randomized controlled trials. In addition, network meta-analysis was performed to compare the relative effects of mono versus combination cilostazol treatments. Results— Ten studies were included in this review, 5 of which were assigned to the cilostazol mono group (n=5429) and the other 5 to the combination group (n=2456). The relative risks of recurrent stroke, ischemic stroke, and composite outcomes with cilostazol mono as well as combination treatments were significantly lower than with SAPT without any significant heterogeneity. An indirect comparison of these 3 outcomes revealed the cilostazol combination approach to be superior. The cilostazol mono treatment diminished hemorrhagic stroke more significantly than SAPT and the cilostazol combination did not increase hemorrhagic stroke compared to SAPT. The outcomes from the 2 cilostazol regimens were comparable to SAPT in the case of myocardial infarction. Conclusions— Cilostazol is a more effective and safer treatment option than SAPT approaches using mainly aspirin. Cilostazol regimens can also be modified to clinical situations as this drug reduces recurrent and ischemic stroke more efficiently as a combination therapy but is more beneficial for hemorrhagic stroke as a monotherapy.