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Efficacy and Safety of Adjunctive Cilostazol to Dual Antiplatelet Therapy After Stent Implantation

Background: Aspirin and clopidogrel dual antiplatelet therapy (DAT) reduce ischemic events in patients with cardiovascular disease. However, recurrent ischemic event occurrence during DAT remains a major concern. This systematic review assesses the efficacy and safety of adjunctive cilostazol to DAT in combination with DAT on reducing clinical adverse events. Methods: We searched randomized controlled trials (RCTs) in PubMed, Embase, Cochrane library, clinicaltrial.gov, and Chinese Biomedical Database through July 2011. Pooled risk ratio (RR) with 95% confidence intervals (CIs) was calculated. Two independent reviewers evaluated the included studies. The extracted data were analyzed by Review Manager 5.1.2 (The Cochrane Collaboration, Oxford, UK) and GRADEprofiler 3.6 (GRADE Working Group). Results: A total of 7 RCTs (4351 patients) were included in the analysis, with a follow-up period of 6 to 12 months. Pooled analysis showed that cilostazol was associated with a significant reduction in major adverse cardiac events (MACEs; pooled RR 0.69, 95% CI 0.52-0.91; P = .008) and repeat revascularization (RR 0.74, 95% CI 0.61-0.89; P = .002); however, cilostazol was not associated with a reduction in the risk of stent thrombosis (RR 1.00, 95% CI 0.41-2.45; P = 1.00). Cilostazol seems to be safe, with no significant increase in the risk of bleeding (RR 1.06, 95% CI 0.72-1.56; P = .77). The 4 outcomes were low-quality evidence for MACE, moderate-quality evidence for repeat revascularization, and high-quality evidence for bleeding and stent thrombosis. Conclusions: When compared to the currently recommended DAT, triple antiplatelet therapy with cilostazol can reduce repeat revascularization with no increase in the risk of bleeding.