Appropriate Duration of Anti-Platelet and Thrombotic Strategy After 12 Months in Patients With Atrial Fibrillation Treated With Drug Eluting Stents

Study Overview
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Brief Summary
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Atrial fibrillation patients with risk factors for stroke and systemic embolism require long-term anticoagulant therapy. Recently, non-vitamin K antagonist oral anticoagulant (NOAC) has shown their excellent safety and efficacy, and thus are widely accepted in clinical practice. Meanwhile, after percutaneous coronary intervention (PCI) using the drug-eluting stents due to coronary artery disease, the administration of one or more antiplatelets is essential to prevent the recurrence of stent thrombosis and myocardial infarction. Combined administration of anticoagulants and antiplatelets significantly lowers the incidence of ischemic events such as stroke and myocardial infarction, however, it also significantly increases the likelihood of bleeding leading to hospitalization, and or even death, thereby significantly affecting the clinical course of the AF patients who underwent PCI. Nevertheless, due to the very high mortality rate of stent thrombosis, the current standard of care guidelines recommend triple therapy with anticoagulants and double antiplatelet therapy (DAPT) in patients with atrial fibrillation for 1 month after coronary intervention, followed by co-administration of NOAC with single antiplatelet agent for 1 year. However, little is known after the optimal therapeutic strategy after 1 year. The purpose of this study is to compare the clinical results of single anticoagulant and clopidogrel combination therapy for maintenance therapy after 1 year in patients with atrial fibrillation.

Detailed Description
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AF patients who had undergone PCI with DES implantation at least 12 months ago will be enrolled in this study. Decision for the antiplatelet agent discontinuation would be determined by randomization. Apixaban or Rivaroxaban would be prescribed to reduced the risk stroke or systemic embolism evoked by AF, and the administration of Warfarin, a vitamin-K dependent anticoagulant, would also be allowed according to attending physician's decision. The following criteria should be followed for the reduction of dosages according to the patient's renal function and other systemic conditions. Warfarin is administered to patients with creatinine clearance < 15 ml/min or dialysis. The drugs used in this study correspond to the international treatment guidelines after coronary intervention in patients with atrial fibrillation.NOAC and antiplatelet agents would be prescribed upon an outpatient visit. Clinical outcome would be followed for 2 years after study enrollment and randomization. Screening Baseline Serum AST/ALT level Creatinine clearance (mL/min) Concurrent administration of CYP3A4 agents: Ketoconazole, Itraconazole, Iopinavir/ritonavir, indinavir/ritonavir, conviaptan # Apixaban Dose Adjustment (patients meeting 2 of 3 criteria): 15 mL/min ≤ eGFR < 30 mL/min or ESRD patients Body weight under 60 kg age over 80 years old. # Rivaroxaban Dose Adjustment (patients with eGFR from 15-49 mg/min): 15 mg for NOAC monotherapy group 10 mg for Dual antithrombotic therapy group

Official Title
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Appropriate Duration of Anti-Platelet and Thrombotic Strategy After 12 Months in Patients With Atrial Fibrillation Treated With Drug Eluting Stents (ADAPT AF-DES)

Conditions
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Atrial Fibrillation

Intervention / Treatment
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* Drug: NOAC monotherapy
* Drug: Dual therapy with apixaban and clopidogrel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: over 19 years old Patient who underwent PCI with DES more than 12 months ago Non-valvular atrial fibrillation patients requiring long-term anticoagulation Exclusion Criteria: Over 85 years old Pregnancy or Potential Pregnancy Life expectancy within 1 year Patients who refuse or do not understand the written consent form Requiring anticoagulation due to history of mechanical valve replacement, mitral stenosis or deep vein thrombosis Coagulopathy, continuous bleeding, or Hb level below 10 g/dL Intracerebral hemorrhage within 2 months Patients with gastrointestinal hemorrhage within three months of registration Patients diagnosed with a gastrointestinal tumor that requires continuous treatment Patients treated with 1st generation drug-eluting stents (Cypher, Taxus, or Endeavor Sprint)

Ages Eligible for Study
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Minimum Age: 19 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Anticoagulation mono therapy<br> | Drug: NOAC monotherapy<br>* Patients enrolled in the anticoagulation mono therapy arm would be administered with apixaban 5 mg twice daily or rivaroxaban 20 mg once daily for 2 years after randomization. In case of renal impairment, reduced dose of apixaban (2.5 mg twice daily) or rivaroxaban (15 mg once daily) or Warfarin would be considered.<br>|
| Active Comparator: Dual antithrombotic therapy<br> | Drug: Dual therapy with apixaban and clopidogrel<br>* Patients enrolled in the dual antithrombotic therapy arm would be administered with apixaban 5 mg twice daily or rivaroxaban 15 mg once daily and clopidogrel 75 mg daily for 2 years after randomization. In case of renal impairment, reduced dose of apixaban (2.5 mg twice daily) or rivaroxaban (10 mg once daily) or Warfarin would be considered.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Net adverse clinical event (NACE) | Death, myocardial infarction, stent thrombosis, stroke, systemic embolism, major or clinically relevant non-major bleeding defined by International Society on Thrombosis and Haemostasis (ISTH) | at 12 months (1 year) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of each component of NACE | -NACE includes all-cause death, myocardial infarction, definite, probable, or possible stent thrombosis, stroke, systemic embolism, and ISTH major or clinically relevant non-major bleeding | Day 1 to 24 months (2 years) | 
| Major or clinically relevant non-major bleeding defined by International Society on Thrombosis and Haemostasis (ISTH) |  | Day 1 to 24 months (2 years) | 
| All-cause death, myocardial infarction, stent thrombosis, stroke, systemic embolism, and ISTH major bleeding |  | Day 1 to 24 months (2 years) | 
| All-cause or cardiovascular death |  | Day 1 to 24 months (2 years) | 
| Major adverse cardiac event (MACE) | -MACE includes all-cause death, myocardial infarction, definite, probable, or possible stent thrombosis, ischemic stroke, and systemic embolism | Day 1 to 24 months (2 years) | 
| Incidence of each component of primary and secondary endpoints |  | Day 1 to 24 months (2 years) |