Adjunctive Cilostazol Versus Double Dose
Clopidogrel After PCI with Drug Eluting Stent : The HOST-ASSURE Randomized Trial
Hyo-Soo Kim, MD/PhD Kyung-Woo Park, Si-Hyuck Kang, Kwang-Soo Cha, Byoung-Eun Park, Jay-Young Rhew, Hui-Kyung Jeon, In-Ho Chae On Behalf of The HOST-ASSURE Trial Investigators Seoul National University Hospital, Seoul, Korea
Case 66/M NSTEMI, Killip class III Left main coronary artery disease
Case Do you think DAT is enough?
Aspirin 100 mg
Clopidogrel 75 mg
Case 4 days after successful PCI with TaxusTM : Subacute stent thrombosis
DAT was not enough to protect this patient.
Aspirin 100 mg
Clopidogrel 75 mg
Then, what is your choice?
What is your choice? DDAT Double-Dose Clopidogrel Dual Antiplatelet Therapy
+
vs.
TAT Triple Antiplatelet Therapy (aspirin + clopidogrel + cilostazol)
+
cilostazol
This is theme of HOST-ASSURE-RCT.
Background • Inhibition of platelet reactivity in the first month post-PCI is critical in preventing thrombotic events. • One-week duration of doubling the dose of clopidogrel was shown to improve outcome at one month compared with conventional dose in ACS patients undergoing PCI.
• Yet in Asia, the adjunctive use of cilostazol to dual antiplatelet therapy (triple antiplatelet therapy, TAT) is used more commonly than doubling the dose of clopidogrel (double-dose dual antiplatelet therapy, DDAT) in high-risk patients. • However, there has been no large scale head-to-head comparison of TAT with DDAT to date with regard to clinical outcome.
Objectives 2x2 Factorial Design
Platelet arm
Stent arm
Triple Antiplatelet Therapy (TAT)
PtCr-EES (PromusTM ElementTM)
vs.
Double-Dose Clopidogrel Dual Antiplatelet Therapy (DDAT)
vs.
CoCr-ZES (Endeavor® Resolute)
Objectives 2x2 Factorial Design
Triple Antiplatelet Therapy (TAT)
vs.
Double-Dose Clopidogrel Dual Antiplatelet Therapy (DDAT)
[Hypothesis] TAT is non-inferior to DDAT regarding net clinical outcome at 1 month
Study Design Prospective, single-blinded, randomized multi-center trial 3,750 All Comers Receiving PCI
40 Centers in Korea
2x2 Factorial Design
Aspirin 300 mg + Clopidogrel 300-600 mg Loading
PtCr-EES arm (N=2,500)
Stent Arm 2:1 Randomization
CoCr-ZES arm (N=1,250)
TAT arm
Anti-Platelet Arm 1:1 Randomization
DDAT arm
(N=1,875)
(N=1,875)
Percutaneous Coronary Intervention 200 mg Cilostazol Loading
No Cilostazol Loading
Aspirin 100 mg QD Clopidogrel 75 mg QD Cilostazol 100mg BID
Aspirin 100 mg QD Clopidogrel 150 mg QD
Net Clinical Outcome at 1 Month Post-PCI (Intention-To-Treat Analysis)
Enrollment Criteria General Inclusion Criteria
Exclusion Criteria
• Age ≥18 years • Ability to verbally confirm understandings of risks, benefits and treatment alternatives with written informed consent prior to any study-related procedure • Significant lesion (>50% by visual estimate) in any of the coronary arteries, venous or arterial bypass grafts • Evidence of myocardial ischemia or diameter stenosis > 70%
• Known hypersensitivity/contraindication to heparin, aspirin, clopidogrel, cilostazol, everolimus, zotarolimus, or contrast media • Systemic (intravenous) Everolimus or Zotarolimus use ≤ 12 months • Female of childbearing potential • History of bleeding diathesis, known coagulopathy (including HIT), abnormal CBC (Hb < 10 g/dL or PLT < 100k /μL) or refusal of blood transfusions • GI or GU bleeding ≤ 3 months or major surgery ≤ 2 months • Life expectancy