Stroke Prevention by Cilostazol in Patients with Atherothrombosis: Meta-analysis of Placebo-controlled Randomized Trials

• Published in: Journal of stroke and cerebrovascular diseases 2009-11, Vol.18 (6), p.482-490
• Main Authors: Uchiyama, Shinichiro, MD, Demaerschalk, Bart M., MD, Goto, Shinya, MD, Shinohara, Yukito, MD, Gotoh, Fumio, MD, Stone, William M., MD, Money, Samuel R., MD, Kwon, Sun Uck, MD
• Format: Article
• Language: English
• Subjects: Aged; Atherosclerosis - complications; Atherosclerosis - drug therapy; Atherosclerosis - mortality; atherothrombosis; Cardiovascular; cerebrovascular disorders; cilostazol; Evidence-Based Medicine; Female; Heart Diseases - etiology; Heart Diseases - prevention & control; Hemorrhage - chemically induced; Humans; Male; Meta-analysis; Middle Aged; Neurology; phosphodiesterase inhibitor; platelet aggregation inhibitor; Platelet Aggregation Inhibitors - adverse effects; Platelet Aggregation Inhibitors - therapeutic use; prevention; Randomized Controlled Trials as Topic; Risk Assessment; stroke; Stroke - etiology; Stroke - mortality; Stroke - prevention & control; Tetrazoles - adverse effects; Tetrazoles - therapeutic use; Thrombosis - complications; Thrombosis - drug therapy; Thrombosis - mortality; Treatment Outcome; vascular endothelium
• ISSN: 1052-3057; 1532-8511
• DOI: 10.1016/j.jstrokecerebrovasdis.2009.07.010

Background Cilostazol is an antiplatelet agent that inhibits phosphodiesterase III in platelets and vascular endothelium. Previous randomized controlled trials of cilostazol for prevention of cerebrovascular events have garnered mixed results. We performed a systematic review and meta-analysis of the randomized clinical trials in patients with atherothrombotic diseases to determine the effects of cilostazol on cerebrovascular, cardiac, and all vascular events, and on all major hemorrhagic events. Methods Relevant trials were identified by searching MEDLINE, EMBASE, and the Cochrane Controlled Trial Registry for titles and abstracts. Data from 12 randomized controlled trials, involving 5674 patients, were analyzed for end points of cerebrovascular, cardiac, and major bleeding events. Searching, determination of eligibility, data extraction, and meta-analyses were conducted by multiple independent investigators. Results Data were available in 3782, 1187, and 705 patients with peripheral arterial disease, cerebrovascular disease, and coronary stenting, respectively. Incidence of total vascular events was significantly lower in the cilostazol group compared with the placebo group (relative risk [RR], 0.86; 95% confidence interval [CI], 0.74-0.99; P =.038). This was particularly influenced by a significant decrease of incidence of cerebrovascular events in the cilostazol group (RR, 0.58; 95% CI, 0.43-0.78; P < .001). There was no significant intergroup difference in incidence of cardiac events (RR, 0.99; 95% CI, 0.83-1.17; P =.908) and serious bleeding complications (RR, 1.00; 95% CI, 0.66-1.51; P =.996). Conclusions This first meta-analysis of cilostazol in patients with atherothrombosis demonstrated a significant risk reduction for cerebrovascular events, with no associated increase of bleeding risk.