Study design and rationale of 'Influence of Cilostazol-based triple anti-platelet therapy on ischemic complication after drug-eluting stent implantation (CILON-T)' study: A multicenter randomized trial evaluating the efficacy of Cilostazol on ischemic vascular complications after drug-eluting stent implantation for coronary heart disease.

Abstract

BACKGROUND:

Current guidelines recommend dual anti-platelet therapy, aspirin and clopidogrel, for patients treated with drug-eluting stent for coronary heart disease. In a few small trials, addition of cilostazol on dual anti-platelet therapy (triple anti-platelet therapy) showed better late luminal loss. In the real-world unselected patients with coronary heart disease, however, the effect of cilostazol on platelet reactivity and ischemic vascular events after drug-eluting stent implantation has not been tested. It is also controversial whether there is a significant interaction between lipophilic statin and clopidogrel.

METHODS/DESIGN:

CILON-T trial was a prospective, randomized, open-label, multi-center, near-all-comer trial to demonstrate the superiority of triple anti-platelet therapy to dual anti-platelet therapy in reducing 6 months' major adverse cardiovascular/cerebrovascular events, composite of cardiac death, nonfatal myocardial infarction, target lesion revascularization and ischemic stroke. It also tested whether triple anti-platelet therapy is superior to dual anti-platelet therapy in inhibiting platelet reactivity in patients receiving percutaneous coronary intervention with drug-eluting stent. Total 960 patients were randomized to receive either dual anti-platelet therapy or triple anti-platelet therapy for 6 months and also, randomly stratified to either lipophilic statin (atorvastatin) or non-lipophilic statin (rosuvastatin) indefinitely. Secondary endpoints included all components of major adverse cardiovascular/cerebrovascular events, platelet reactivity as assessed by VerifyNow P2Y12 assay, effect of statin on major adverse cardiovascular/cerebrovascular events, bleeding complications, and albumin-to-creatinine ratio to test the nephroprotective effect of cilostazol. Major adverse cardiovascular/cerebrovascular events will also be checked at 1, 2, and 3 years to test the 'legacy' effect of triple anti-platelet therapy that was prescribed for only 6 months after percutaneous coronary intervention.

DISCUSSION:

CILON-T trial will give powerful insight into whether triple anti-platelet therapy is superior to dual anti-platelet therapy in reducing ischemic events and platelet reactivity in the real-world unselected patients treated with drug-eluting stent for coronary heart disease. Also, it will verify the laboratory and clinical significance of drug interaction between lipophilic statin and clopidogrel.

TRIAL REGISTRATION:

National Institutes of Health Clinical Trials Registry (ClinicalTrials.gov identifier# NCT00776828).

• Authors: Seung-Pyo Lee, Jung-Won Suh, Kyung Woo Park, Hae-Young Lee, Hyun-Jae Kang, Bon-Kwon Koo, In-Ho Chae, Dong-Ju Choi, Seung-Woon Rha, Jang-Whan Bae, Myeong-Chan Cho, Taek-Geun Kwon, Jang-Ho Bae, Hyo-Soo Kim, CILON-T investigators
• Journal: Trials (Trials) Vol. 11 Pg. 87 (Aug 24 2010) ISSN: 1745-6215 [Electronic] England
• PMID: 20735821 (Publication Type: Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Hydroxymethylglutaryl-CoA Reductase Inhibitors
• Platelet Aggregation Inhibitors
• Tetrazoles
• Clopidogrel
• Cilostazol
• Ticlopidine
• Aspirin

Topics

• Angioplasty, Balloon, Coronary (adverse effects, instrumentation, mortality)
• Aspirin (therapeutic use)
• Brain Ischemia (etiology, mortality, prevention & control)
• Cilostazol
• Clinical Protocols
• Clopidogrel
• Drug Interactions
• Drug Therapy, Combination
• Drug-Eluting Stents
• Humans
• Hydroxymethylglutaryl-CoA Reductase Inhibitors
• Myocardial Infarction (etiology, prevention & control)
• Myocardial Ischemia (etiology, mortality, prevention & control)
• Platelet Aggregation Inhibitors (adverse effects, therapeutic use)
• Prospective Studies
• Prosthesis Design
• Republic of Korea
• Research Design
• Stroke (etiology, prevention & control)
• Tetrazoles (adverse effects, therapeutic use)
• Ticlopidine (analogs & derivatives, therapeutic use)
• Time Factors
• Treatment Outcome