Atrial Fibrillation
Conditions
Brief summary
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
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 reduce 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 \# Dose Adjustment Criteria for Apixaban @ Meeting 2 of 3 following criteria * Serum creatinine level \> 1.5 mg/dL * Body weight under 60 kg * age over 80 years old \# Dose Adjustment Criteria for Rivaroxaban * eGFR from 15-49 mg/min
Interventions
DRUGNOAC monotherapy
Patients enrolled in the NOAC monotherapy arm would be administered with apixaban 5 mg twice daily or rivaroxaban 20 mg once daily for 2 years after randomization. Reduced dose of apixaban (2.5 mg twice daily) or rivaroxaban (15 mg once daily) will be used in patients meeting the pre-defined criteria for dose reduction. Warfarin is allowed to use at the physicians' discretion.
DRUGDual antithrombotic therapy with NOAC and clopidogrel
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. Reduced dose of apixaban (2.5 mg twice daily) or rivaroxaban (10 mg once daily) will be used in patients meeting the pre-defined criteria for dose reduction. Warfarin is allowed to use at the physicians' discretion.
Sponsors
Yonsei University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
19 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
1. over 19 years old 2. Patient who underwent PCI with DES more than 12 months ago 3. Non-valvular atrial fibrillation patients requiring long-term anticoagulation
Exclusion criteria
1. Over 85 years old 2. Pregnancy or Potential Pregnancy 3. Life expectancy within 1 year 4. Patients who refuse or do not understand the written consent form 5. Requiring anticoagulation due to history of mechanical valve replacement, mitral stenosis or deep vein thrombosis 6. Coagulopathy, continuous bleeding, or Hb level below 10 g/dL 7. Intracerebral hemorrhage within 2 months 8. Patients with gastrointestinal hemorrhage within three months of registration 9. Patients diagnosed with a gastrointestinal tumor that requires continuous treatment 10. Patients treated with 1st generation drug-eluting stents (Cypher, Taxus, or Endeavor Sprint)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Net adverse clinical event (NACE) | at 12 months (1 year) | All-cause death, myocardial infarction, stent thrombosis, stroke, systemic embolism, major or clinically relevant non-major bleeding defined by International Society on Thrombosis and Haemostasis (ISTH) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Each component of NACE | Day 1 to 12 months (1 year) | 1\) all-cause death; 2) myocardial infarction; 3) stent thrombosis; 4) stroke; 5) systemic embolism; 6) ISTH major bleeding; 7) ISTH clinically relevant non-major bleeding |
| ISTH major or clinically relevant non-major bleeding | Day 1 to 12 months (1 year) | — |
| All-cause death, myocardial infarction, stent thrombosis, stroke, systemic embolism, and ISTH major bleeding | Day 1 to 12 months (1 year) | — |
| Cardiovascular death | Day 1 to 12 months (1 year) | — |
| Cardiovascular death, myocardial infarction, stent thrombosis, ischemic stroke, and systemic embolism | Day 1 to 12 months (1 year) | — |
| Primary outcome (NACE) at 2 years | Day 1 to 24 months (2 years) | — |
Countries
South Korea
Outcome results
None listed