Additional Benefit of Cilostazol to Dual Antiplatelet Therapy After Biolimus-eluting Stent Implantation
- Conditions
- Coronary Artery Disease
- Interventions
- Registration Number
- NCT01192724
- Lead Sponsor
- Yonsei University
- Brief Summary
Because there is limited data about long-term efficacy and safety about short-term use of cilostazol adding to dual antiplatelet therapy in patients with long or multivessel coronary artery disease after 2nd generation DES implantation, especially in biodegradable polymer stent, the investigators will evaluate whether a 3-month use of cilostazol in addition to dual antiplatelet therapy effectively reduces clinical adverse outcome at 1 year in subject with long or multivessel coronary artery disease after biolimus-eluting stent implantation.
- Detailed Description
Previous randomized trials have shown the efficacy of drug-eluting stent (DES) such as sirolimus-eluting stent (CYPHERTM, Cordis, Warren, NJ, USA), paclitaxel-eluting stent (TAXUSTM, BostonScientific, Natick, MA, USA), and zotarolimus-eluting stent (Endeavor,Medtronic,Minneapolis, MN, USA) over bare metal stents (BMS) in reducing neointimal hyperplasia, late luminal loss, and angiographic restenosis leading to decreased target lesion revascularization.1-4 In addition, Among patients with off-label indications, the use of DESs reduced a rate of repeat revascularization without increasing the risk of death or myocardial infarction, as compared with bare-metal stents.5 But, compared with on-label use, off-label use of DESs is associated with a higher rate of adverse outcomes such as death, myocardial infarction and target vessel revascularization. Furthermore, stent thrombosis (ST) occurred predominantly in patients who underwent off-label DES implantation.6 It is known that the risk of adverse cardiac events and ST after DES implantation is related to stent length.7 Cilostazol is a potent phosphodiesterase III inhibitor preventing the hydrolysis of cAMP in platelets and vascular smooth muscle cell. The novel mechanism of action of cilostazol reduces the number of circulating, partially activated, or preconditioned platelets, by reducing the surface expression of adhesive molecules in endothelial cells interacting with circulating platelets. The agent also directly inhibits platelet aggregation induced by a variety of stimuli, including arachidonic acid, ADP, collagen, thrombin, and high shear stress.8 In current guidelines, a 12-month duration of dual antiplatelet therapy with aspirin and clopidogrel is recommended after DES implantation.9 But, recent meta-analyses showed a potential benefit of cilostazol in addition to dual antiplatelet therapy in reducing angiographic restenosis and improved clinical outcomes after BMS or DES implantation.10, 11 Actually, additional cilostazol to dual antiplatelet therapy showed reduced restenosis and late loss in patients with long coronary lesion and diabetes with multivessel coronary artery disease and it also showed beneficial effect on stent thrombosis after DES implantation.12-14 Although most studies showed no difference in bleeding according to additional cilostazol to dual antiplatelet therapy, the rate of early cessation of cilostazol due to adverse effect including headache, palpitation, skin rash and hepatic dysfunction was about 15%.12-14 Because of relatively higher side effect rate and no definitive duration of addition cilostazol use, we expect that cilostazol with short duration can be easily accepted to patient. Although almost studies about cilostazol after stent implantation used a 6- month duration of cilostazol, one study showed that use of cilostazol for 3 months after percutaneous transluminal coronary balloon angioplasty reduced restenosis and revascularization, as compared with use of aspirin.15 So, we expect a 3-month use of additional cilostazol to dual antiplatelet therapy can reduce the adverse outcome and ST after stent implantation without increasing early cessation of cilostazol.
The BioMatrixTM stent system (Biosensors Interventional Technologies Pte., Ltd, Singapore) consist of a stainless steel, quadrature-link design, balloon expandable S-StentTM, and a polylactic acid (PLA) polymer and BiolimusA9® coating mounted on a low-profile delivery catheter.16, 17 It is expected that abluminal biodegradable coating of BioMatrixTM stent can lead to more targeted drug release, reduced systemic exposure and early BMS-like endothelial coverage.18 The first-in-man, randomized controlled SEALTH I trial demonstrate higher efficacy of BioMatrixTM stent by showing lower late lumen loss and in-stent restenosis as compared with BMS, S-stent at 6-month follow-up.19 In LEADERS trial, BioMatrixTM stent showed similar efficacy and safety as compared with sirolimus-eluting stent in patients with chronic stable coronary artery disease and acute coronary syndromes.20 But significantly lower uncovered and malapposed struts was detected by optical coherence tomography study.21 This means more complete coverage of struts and we can expect lower late ST after BioMatrixTM stent implantation.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 630
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Triple antiplatelet therapy (TAPT) group Cilostazol 3-month use of cilostazol in addition to dual antiplatelet agent Triple antiplatelet therapy (TAPT) group Aspirin 3-month use of cilostazol in addition to dual antiplatelet agent Dual antiplatelet therapy (DAPT) group Aspirin Aspirin and clopidogrel (dual antiplatelet therapy, DAPT) for 1 year Dual antiplatelet therapy (DAPT) group Clopidogrel Aspirin and clopidogrel (dual antiplatelet therapy, DAPT) for 1 year Triple antiplatelet therapy (TAPT) group Clopidogrel 3-month use of cilostazol in addition to dual antiplatelet agent
- Primary Outcome Measures
Name Time Method Device-oriented composite One year Device-oriented composite was defined as a composite of cardiac death, MI (not clearly attributable to a non-target vessel), and clinically indicated target lesion revascularization (TLR).
- Secondary Outcome Measures
Name Time Method Patient-oriented composite One year Patient-oriented composite was defined as a composite of all-cause mortality, any MI (includes non-target vessel territory), and any repeat revascularization (includes all target and non-target vessel).
Each component of device- and patient-oriented composite One year All-cause mortality, cardiac death, any myocardial infarction (MI), MI (not clearly attributable to a non-target vessel), clinically indicated target lesion revascularization (TLR), and any repeat revascularization (includes all target and non-target vessel)
Academic Research Consortium (ARC) defined stent thrombosis One year definite, probable, and possible stent thrombosis / acute, subacute, and late stent thrombosis
Safety assessments One year Safety assessments will be performed for bleeding complication according to Thrombolysis In Myocardial Infarction (TIMI) criteria, medication compliance, side effect of drug, and heart rate.
Trial Locations
- Locations (1)
Wonju Christian Hospital
🇰🇷Wonju, Gangwon, Korea, Republic of