January 1, 2011Journal of the American College of Cardiology
Multicenter Randomized Trial Evaluating the Efficacy of Cilostazol on Ischemic Vascular Complications After Drug-Eluting Stent Implantation for Coronary Heart Disease
Key result
Triple antiplatelet therapy with cilostazol did not show superiority over dual antiplatelet therapy in reducing adverse cardiovascular outcomes after DES implantation (8.5% vs 9.2%; HR 0.90, p=0.74).
Why the study?
The addition of cilostazol to dual antiplatelet therapy reduces platelet reactivity, but its clinical benefits in real-world patients receiving intracoronary drug-eluting stents needed evaluation.
Does the addition of cilostazol to dual antiplatelet therapy (aspirin and clopidogrel) reduce the composite of cardiac death, nonfatal myocardial infarction, ischemic stroke, or target lesion revascularization in patients receiving drug-eluting stents?
Key Points
- To assess the efficacy of cilostazol in reducing ischemic vascular complications following drug-eluting stent implantation in patients with coronary heart disease.
- Multicenter randomized trial design
- Patients undergoing drug-eluting stent implantation were assigned to receive cilostazol or placebo
- Primary endpoints included rates of ischemic vascular complications over a specified follow-up period.
Study Design
Type
RCT (n=960)
Randomization
randomized
Multicenter
Yes
Structured PICO
Does the addition of cilostazol to dual antiplatelet therapy (aspirin and clopidogrel) reduce the composite of cardiac death, nonfatal myocardial infarction, ischemic stroke, or target lesion revascularization in patients receiving drug-eluting stents?
P
Population
960 patients who received intracoronary drug-eluting stents, randomized to dual or triple antiplatelet therapy for 6 months.
I
Intervention
Triple antiplatelet therapy (TAT) consisting of aspirin, clopidogrel, and cilostazol for 6 months
C
Comparator
Dual antiplatelet therapy (DAT) consisting of aspirin and clopidogrel for 6 months
O
Outcome
Composite of cardiac death, nonfatal myocardial infarction, ischemic stroke, or target lesion revascularization (TLR) at 6 monthscomposite
Main Result
Hazard Ratio: 0.9 (95% CI 0.54–1.52)
Absolute Event Rate: 8.5% vs 9.2%
p-value: p=0.74
Adding cilostazol to conventional dual antiplatelet therapy after drug-eluting stent implantation reduces platelet reactivity but does not improve clinical cardiovascular outcomes at 6 months.
Key expert perspectives
Captured external expert commentary on this paper, strongest first. Original sources are linked where available.
“I think there probably is some antiproliferative effect of cilostazol—a number of studies have suggested this. The meta-analysis shows with some confidence that there's a reduction in TLR, but there's no effect on hard events like MI and death, and then you pay a price in terms of tolerability.”
“the accumulation of minor side effects may cause a critical situation due to cilostazol termination in a larger number of patients in real-world settings”
Implication
Does not support cilostazol addition to DAPT after DES; challenges earlier reports of ischemic benefit.
Abstract
OBJECTIVES: We aimed to test whether cilostazol has beneficial effects in the real-world patients treated with intracoronary drug-eluting stents (DES). BACKGROUND: The addition of cilostazol on the conventional dual antiplatelet therapy has been reported to reduce platelet reactivity and to improve clinical outcomes after percutaneous coronary intervention in previous studies. METHODS: In a randomized multicenter trial, we enrolled 960 patients who received DES. They were randomized to receive either dual antiplatelet therapy (DAT) (aspirin and clopidogrel) or triple antiplatelet therapy (TAT) (aspirin, clopidogrel, and cilostazol) for 6 months. Primary end point was the composite of cardiac death, nonfatal myocardial infarction, ischemic stroke, or target lesion revascularization (TLR). Secondary end points were P2Y₁₂ reaction unit (PRU) measured with the VerifyNow P2Y12 assay (Accumetrics, San Diego, California) at discharge and at 6 months after the index procedure. All-cause death, stent thrombosis, and each component of the primary end point at 6 months were other secondary end points. Analysis was done on an intention-to-treat basis. RESULTS: At 6 months' follow-up, there was no difference in the primary end point between the 2 groups (8.5% in TAT vs. 9.2% in DAT, p = 0.74). In secondary end point analysis, the TAT group achieved lower PRU levels than the DAT group both at discharge (206.6 ± 90.3 PRU vs. 232.2 ± 80.3 PRU, p < 0.001) and at 6 months (210.7 ± 87.9 PRU vs. 255.7 ± 73.7 PRU, p < 0.001). In the Cox proportional hazards analysis, lesion length (≥28 mm, hazard ratio [HR]: 2.10, 95% confidence interval [CI]: 1.25 to 3.52), and PRU level at discharge (every increase in tertile, HR: 1.61, 95% CI: 1.16 to 2.25) were predictors of the primary end point, but not the use of cilostazol (HR: 0.90, 95% CI: 0.54 to 1.52). CONCLUSIONS: Despite the greater reduction of platelet reactivity by addition of cilostazol to conventional DAT, TAT did not show superiority in reducing the composite of adverse cardiovascular outcomes after DES implantation. (The Efficacy of CILostazol ON Ischemic Complications After DES Implantation [CILON-T]; NCT00776828).
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Cite This Study
Suh et al. (2011) conducted an RCT in Coronary Heart Disease (n=960). Triple antiplatelet therapy (aspirin, clopidogrel, and cilostazol) vs. Dual antiplatelet therapy (aspirin and clopidogrel) was evaluated on Composite of cardiac death, nonfatal myocardial infarction, ischemic stroke, or target lesion revascularization (TLR) (HR 0.90, 95% CI 0.54 to 1.52, p=0.74). Triple antiplatelet therapy with cilostazol did not show superiority over dual antiplatelet therapy in reducing adverse cardiovascular outcomes after DES implantation (8.5% vs 9.2%; HR 0.90, p=0.74).