Triple Versus Dual Antiplatelet Therapy After ABT578-Eluting Stent

Official Title: “Comparison of Triple Versus Dual Antiplatelet Therapy After ABT578-Eluting Stent Implantation For Long Coronary Lesions”

To evaluate whether the cilostazol reduce neointimal hyperplasia after ZES (Zotarolimus-eluting stents) implantation, the investigators performed double-blind,randomized, multicenter, prospective study compared triple antiplatelet therapy (aspirin plus clopidogrel plus cilostazol) and dual antiplatelet therapy (aspirin plus clopidogrel) for 8 months in patients with long coronary lesion treated with ZES.

Use of drug-eluting stent (DES) has reduced the incidence of restenosis rate and the need for repeat revascularization compared to using bare metal stents. DES implantation also significantly reduced the angiographic restenosis in patients with long coronary lesions.However, although the use of DES has decreased the effect of lesion length on restenosis, the restenosis after DES implantation of long coronary lesions remain at a higher risk of restenosis.

Cilostazol, a phosphodiesterase III inhibitor, has been known to reduce smooth muscle proliferation and intimal hyperplasia after endothelial injury and restenosis after balloon angioplasty and bare-metal stent (BMS) implantation when compared with aspirin and clopidogrel or ticlopidine. Recently, the impact of 6-month cilostazol treatment in addition to aspirin and clopidogrel on neointimal hyperplasia after sirolimus-(SES) or paclitaxel-eluting stent (PES) implantation for long-coronary lesions has been evaluated in our institution. It reported that cilostazol treatment achieved primary end point (in-stent late loss) and reduced need of target lesion revascularization without significant adverse drug-side effects with open-label design, which suggest that 6-month treatment of cilostazol effectively inhibits the neointimal hyperplasia after DES implantation and can be safely applied to the patients or lesions with higher risk of restenosis such as diabetes and long lesions.However, our study was done in unblinded manner and might underestimate the angiographic results due to relatively short-term follow-up angiographic follow-up(6-month.

Recently commercially available new-DES, zotarolimus-eluting stent (ZES) demonstrated significant reduction of restenosis and cardiac events during 9-month. However, it has not been tested that 8-month treatment of cilostazol also effectively inhibits the neointimal hyperplasia after ZES implantation in patients with long coronary lesions. Therefore, to evaluate whether the cilostazol reduce neointimal hyperplasia after ZES implantation, the investigators performed double-blind, randomized, multicenter, prospective study compared triple antiplatelet therapy (aspirin plus clopidogrel plus cilostazol) and dual antiplatelet therapy (aspirin plus clopidogrel) for 8 months in patients with long coronary lesion treated with ZES.

Intervention(s) in this Clinical Trial

• Drug: cilostazol
  • cilostazol 200mg loading dose within 1 hours after successful stenting, followed by 100mg bid for 8 months
• Drug: placebo
  • placebo 200mg loading dose within 1 hours after successful stenting, followed by 100mg bid for 8 months

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: cilostazol
  • Cilostazol 200mg loading dose within 1 hours after successful stenting, followed by 100mg bid for 8 months
• Placebo Comparator: placebo
  • Control placebo 200mg loading dose within 1 hours after successful stenting, followed by 100mg bid for 8 months

Primary Measures

• Angiographic in-stent late loss
  • Time Frame: 8-months after randomization
    Safety Issue?: No

Secondary Measures

• Composite of death, MI, and target lesion or vessel revascularization at 12 months, In-stent and in-stent restenosis at 8 months, In-segment late loss at 8 months Adverse side effects during treatment
  • Time Frame: 12 months
    Safety Issue?: Yes

Inclusion Criteria:

• 1. Clinical 1) Patients with angina and documented ischemia or patients with documented silent ischemia 2) Patients who are eligible for intracoronary stenting 3) Age >18 years, <75 ages
• 2. Angiographic 1) De novo lesion 2) Percent diameter stenosis ≥50% 3) Reference vessel size >2.5 mm by visual estimation 4) Lesion length >25 mm by visual estimation that is required for long Endeavor stent implantation (planned total stent length >30mm)

Exclusion Criteria:

• 1. History of bleeding diathesis or coagulopathy
• 2. Pregnant
• 3. Known hypersensitivity or contra-indication to contrast agent, heparin, sirolimus and paclitaxel
• 4. Limited life-expectancy (less than 1 year) due to combined serious disease
• 5. ST-elevation acute myocardial infarction
• 6. Characteristics of lesion 1) Left main disease 2) In-stent restenosis 3) Graft vessels
• 7. Hematological disease (Neutropenia <3000/mm3, Thrombocytopenia <100,000/mm3)
• 8. Hepatic dysfunction, liver enzyme (ALT and AST) elevation >3 times normal
• 9. Renal dysfunction, creatinine >2.0mg/dL
• 10. Contraindication to aspirin, clopidogrel or cilostazol
• 11. planned bifurcation stenting

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 75 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Investigator: CardioVascular Research Foundation, Korea Other

Overall Clinical Trial Officials and Contacts

Seung-Wook Park, MD,PhD Principal Investigator Department of Medicine, Asan Medical Center, University of Ulsan College of Medicine  

Information obtained from ClinicalTrials.gov on February 12, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00589927

Study ID Number: 2007-0003

ClinicalTrials.gov Identifier: NCT00589927

Health Authority: South Korea: Korea Food and Drug Administration (KFDA)