Cilostazol added to aspirin and clopidogrel reduces revascularization without increases in major adverse events in patients with drug-eluting stents: a meta-analysis of randomized controlled trials.
BACKGROUND
The effects of cilostazol added to aspirin and clopidogrel (triple antiplatelet therapy: TAT) on clinical outcomes after drug-eluting stent (DES) implantation are unknown.


METHODS
We conducted a meta-analysis of randomized controlled trials (RCTs) comparing TAT with aspirin and clopidogrel (dual antiplatelet therapy: DAT) in DES patients. Clinical end points were target lesion (TLR) and/or vessel (TVR) revascularization, death, myocardial infarction (MI), stent thrombosis (ST), bleeding, rash, gastrointestinal (GI) side effects, and drug discontinuation. We calculated the pooled estimate based on a fixed-effects model using Peto odds ratio (OR) for rare events. If heterogeneity was observed across an individual RCT, an analysis based on a random-effects model was performed.


RESULTS
Eight RCTs were included in this meta-analysis, involving 3590 patients (TAT:DAT=1800:1790). Up to 24 months, TAT showed a significant reduction in TLR (OR: 0.58, 95% confidence interval (CI): 0.43 to 0.78, p<0.001) and TVR (OR: 0.58, 95% CI: 0.40 to 0.83, p=0.003) compared with DAT. The incidence of death, MI, ST, or overall or major bleeding was comparable between the 2 groups, whereas the proportion of rash (OR: 2.50, 95% CI: 1.52 to 4.10, p<0.001), GI side effects (OR: 3.14, 95% CI: 1.79 to 5.50, p<0.001), or drug discontinuation (OR: 6.81, 95% CI: 2.12 to 21.86, p<0.001) was higher in TAT than DAT.


CONCLUSIONS
In this meta-analysis, TAT was associated with significantly effective outcomes for TLR and TVR without any increase in major adverse events but was associated with tolerance issues compared with DAT after DES implantation.
Department of Planning, Information and Management, The University of Tokyo Hospital, Tokyo, Japan.
Ryota
R
Sakurai
Bon-Kwon
BK
Koo
Hideaki
H
Kaneda
Heidi N
HN
Bonneau
Ryozo
R
Nagai
D001241:Aspirin / Q000008:administration & dosage* / Q000009:adverse effects; D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000628:therapy; D000077407:Cilostazol; D000077144:Clopidogrel; D023903:Coronary Restenosis / Q000453:epidemiology / Q000517:prevention & control*; D004359:Drug Therapy, Combination; D054855:Drug-Eluting Stents / Q000009:adverse effects; D006801:Humans; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000009:adverse effects; D016032:Randomized Controlled Trials as Topic / Q000379:methods; D013777:Tetrazoles / Q000008:administration & dosage* / Q000009:adverse effects; D013988:Ticlopidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*
D010975:Platelet Aggregation Inhibitors; D013777:Tetrazoles; D000077144:Clopidogrel; D000077407:Cilostazol; D013988:Ticlopidine; D001241:Aspirin