Stroke prevention by cilostazol in patients with atherothrombosis: meta-analysis of placebo-controlled randomized trials.
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.
Uchiyama
Shinichiro
S
Department of Neurology, Tokyo Women's Medical University School of Medicine, Shinjuku-ku, Tokyo, Japan. suchiyam@nij.twmu.ac.jp
Demaerschalk
Bart M
BM
Goto
Shinya
S
Shinohara
Yukito
Y
Gotoh
Fumio
F
Stone
William M
WM
Money
Samuel R
SR
Kwon
Sun Uck
SU
D000368:Aged; D050197:Atherosclerosis / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D000077407:Cilostazol; D019317:Evidence-Based Medicine; D005260:Female; D006331:Heart Diseases / Q000209:etiology / Q000517:prevention & control; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D008297:Male; D008875:Middle Aged; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D018570:Risk Assessment; D020521:Stroke / Q000209:etiology / Q000401:mortality / Q000517:prevention & control*; D013777:Tetrazoles / Q000009:adverse effects / Q000627:therapeutic use*; D013927:Thrombosis / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D016896:Treatment Outcome
D010975:Platelet Aggregation Inhibitors; D013777:Tetrazoles; D000077407:Cilostazol