CILostazol-based triple anti-platelet therapy ON Ischemic Complication after drug-eluting stenT implantation - CILON-T


Multiple recent studies have demonstrated that hypo- or non-responsiveness to clopidogrel is associated with adverse clinical outcomes after percutaneous coronary intervention (PCI). Cilostazol is a phosphodiesterase IIIA enzyme antagonist that has been shown to reduce clinical events in small studies of patients undergoing PCI. The current trial sought to investigate whether triple antiplatelet therapy (TAT) with cilostazol, aspirin, and clopidogrel is superior to dual antiplatelet therapy (DAT) in reducing clinical events in patients undergoing PCI. It also sought to assess the efficacy of cilostazol in overcoming clopidogrel hypo- or non-responsiveness.


TAT would be superior to DAT in reducing clopidogrel hypo- or non-responsiveness (as assessed by the VerifyNow assay), as well as clinical events, in real-world patients undergoing PCI.

Study Design

  • Factorial

Patients Enrolled: 915
Mean Follow Up: 6 months
Mean Patient Age: 62.8 years
Female: 32

Patient Populations:

  • Age 18-80 years
  • All-comers: patients with native de-novo coronary artery lesions for which DES implantation was feasible


  • Hepatic dysfunction (SGOT/SGPT >3x upper limit of normal)
  • Renal dysfunction (serum creatinine >2.0 mg/dl or on dialysis)
  • Left ventricular dysfunction (ejection fraction <30%)
  • Uncontrolled hematological disease
  • Patients taking warfarin or other antiplatelet agents
  • Allergy to study medications

Primary Endpoints:

  • Composite of clinical outcomes within 6 months (cardiac death, MI, ischemic stroke, and TLR)

Secondary Endpoints:

  • PRU level measured at discharge and 6 months after the index procedure
  • All-cause death, stent thrombosis, and each component of the primary endpoint at 6 months
  • Bleeding complications according to TIMI criteria
  • The incidence of drug discontinuation
  • Heart rate

Drug/Procedures Used:

Patients were randomized to either TAT with aspirin, clopidogrel, and cilostazol or DAT with aspirin and clopidogrel, for a duration of 6 months following PCI. Aspirin was used at a dose of 100-200 mg daily, whereas clopidogrel was given as a 300-600 mg loading dose, followed by 75 mg daily as maintenance therapy. Cilostazol was given as a 200 mg loading dose, followed by 100 mg BID as maintenance therapy.

Concomitant Medications:

Statin (99%), beta-blocker (52%), angiotensin-converting enzyme inhibitor (41%), proton pump inhibitor (2.5%)

Principal Findings:

A total of 915 patients were randomized, 457 to TAT, and 458 to DAT. Baseline characteristics were fairly similar between the two arms. About 33% of the patients were diabetic, 7.5% had undergone prior PCI, and 2% had undergone prior coronary artery bypass grafting (CABG). About 40% of the patients had stable angina, and 10.3% had a myocardial infarction (MI). Ostial lesions were noted in about 24% of the patients, whereas bifurcation lesions were noted in 30%. About 8% of the patients had thrombus on initial angiography. The mean lesion length was 21.1 mm, with a mean reference vessel diameter of 2.95 mm. The mean number of stents per lesion was 1.2, and about 35% of the patients underwent multivessel PCI. The majority of stents used were either PES (49.5%) or ZES (44%).

The mean P2Y12 reaction unit (PRU), as assessed by the VerifyNow assay, was significantly reduced with TAT as compared with DAT, both at discharge (206.6 vs. 232.1) and after 6 months (210.7 vs. 255.7) (p < 0.001 for both). The primary endpoint of cardiovascular death death, nonfatal MI, ischemic stroke, and target vessel revascularization (TLR) was similar between the TAT and DAT arms (8.5% vs. 9.2%, p = 0.73). Secondary outcomes, including all-cause mortality (0.9% vs. 1.3%, p = 0.75), nonfatal MI (0.9% vs. 0.7%, p = 0.73), ischemic stroke (1.1% vs. 0.9%, p = 0.75), TLR (6.6% vs. 7.2%, p = 0.79), and definite stent thrombosis (0.7% vs. 1.1%, p = 0.73) were similar between the TAT and DAT arms, respectively.

Bleeding complications, including major (0.4% vs. 0.2%) and minor (0.2% vs. 0%), were similar between the two arms (p = 0.51). Drug discontinuation was significantly higher in the TAT arm (6.6% vs. 0.7%, p < 0.001). Platelet assay studies demonstrated that despite a reduction in PRU with cilostazol, there were still a substantial portion of patients who were hypo- or non-responsive, as demonstrated by higher PRUs. These patients had a higher clinical event rate, irrespective of antiplatelet regimen.


The results of this trial indicate that TAT with cilostazol, aspirin, and clopidogrel is not superior to DAT with aspirin and clopidogrel in reducing clinical events 6 months after PCI, even though TAT is associated with a significant decrease in the PRUs, as compared with DAT. However, this trial does demonstrate the potential for utilizing platelet assay studies in routine practice after PCI, since patients with higher PRUs had more clinical events, irrespective of antiplatelet strategy. Other strategies (higher loading doses, BID clopidogrel) and agents (prasugrel) have shown some promise in clinical trials in reducing PRUs and clinical events.


Presented by Dr. Hyo-Soo Kim at the ACC.10/i2 Summit, Atlanta, GA, March 2010.

Suh JW, Lee SP, Park KW, et al. Multicenter randomized trial evaluating the efficacy of cilostazol on ischemic vascular complications after drug-eluting stent implantation for coronary heart disease: results of the CILON-T (influence of CILostazol-based triple antiplatelet therapy ON ischemic complication after drug-eluting stenT implantation) trial. J Am Coll Cardiol. 2011 Jan 18;57(3):280-9.

Clinical Topics: Cardiac Surgery, Invasive Cardiovascular Angiography and Intervention, Stable Ischemic Heart Disease, Aortic Surgery, Cardiac Surgery and SIHD, Chronic Angina

Keywords: Myocardial Infarction, Stroke, Platelet Aggregation Inhibitors, Angina, Stable, Coronary Disease, Ticlopidine, Blood Platelets, Piperazines, Phosphoric Diester Hydrolases, Tetrazoles, Stents, Percutaneous Coronary Intervention, Thrombosis, Coronary Vessels, Coronary Artery Bypass, Diabetes Mellitus

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