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.
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
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.


CONCLUSIONS
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.


BACKGROUND
National Institutes of Health Clinical Trials Registry (ClinicalTrials.gov identifier# NCT00776828).
Lee
Seung-Pyo
SP
Cardiovascular Center, Seoul National University Hospital, Seoul, Korea. jhbae@kyuh.co.kr.
Suh
Jung-Won
JW
Park
Kyung Woo
KW
Lee
Hae-Young
HY
Kang
Hyun-Jae
HJ
Koo
Bon-Kwon
BK
Chae
In-Ho
IH
Choi
Dong-Ju
DJ
Rha
Seung-Woon
SW
Bae
Jang-Whan
JW
Cho
Myeong-Chan
MC
Kwon
Taek-Geun
TG
Bae
Jang-Ho
JH
Kim
Hyo-Soo
HS
D015906:Angioplasty, Balloon, Coronary / Q000009:adverse effects / Q000295:instrumentation* / Q000401:mortality; D001241:Aspirin / Q000627:therapeutic use; D002545:Brain Ischemia / Q000209:etiology / Q000401:mortality / Q000517:prevention & control*; D000077407:Cilostazol; D002985:Clinical Protocols; D000077144:Clopidogrel; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D054855:Drug-Eluting Stents; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D009203:Myocardial Infarction / Q000209:etiology / Q000517:prevention & control; D017202:Myocardial Ischemia / Q000209:etiology / Q000401:mortality / Q000517:prevention & control*; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D011446:Prospective Studies; D011474:Prosthesis Design; D056910:Republic of Korea; D012107:Research Design; D020521:Stroke / Q000209:etiology / Q000517:prevention & control; D013777:Tetrazoles / Q000009:adverse effects / Q000627:therapeutic use*; D013988:Ticlopidine / Q000031:analogs & derivatives / Q000627:therapeutic use; D013997:Time Factors; D016896:Treatment Outcome
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D010975:Platelet Aggregation Inhibitors; D013777:Tetrazoles; D000077144:Clopidogrel; D000077407:Cilostazol; D013988:Ticlopidine; D001241:Aspirin