AF - Atrial Fibrillation, Myocardial Infarction (MI), NSTEMI - Non-ST-Segment Elevation Myocardial Infarction, ST-Segment Elevation Myocardial Infarction(STEMI)
Conditions
Keywords
AF, Myocardial infarction, STEMI, NSTEMI, DOAC, NOAC, OAC alone
Brief summary
The aim of the study is to compare clinical outcomes between direct oral anticoagulant (DOAC) monotherapy versus dual antithrombotic therapy (DOAC plus clopidogrel) in patients with atrial fibrillation and acute myocardial infarction after percutaneous coronary intervention (PCI).
Detailed description
Advancements in device technologies for PCI and adjunct pharmacotherapy have recently shifted research focus toward balancing bleeding risk reduction with the management of ischemic events through novel antithrombotic strategies. These trends are particularly relevant for patients with atrial fibrillation (AF) who require lifelong oral anticoagulation to prevent embolic events. Traditionally, the combination of vitamin K antagonists (such as warfarin) with antiplatelet agents has been regarded as the standard approach to mitigate ischemic risk following PCI in patients with AF. However, previous studies have consistently demonstrated that dual antithrombotic therapy (DAT) utilizing direct oral anticoagulants (DOACs) results in reduced bleeding complications compared to triple antithrombotic therapy based on warfarin. For long-term maintenance, DOAC monotherapy is recommended, as a Class I, after 6 to 12 months post-PCI for patients with stable coronary artery disease (CAD) and AF. Recent randomized clinical trials corroborate these recommendations. The AFIRE (Atrial Fibrillation and Ischemic Events with Rivaroxaban in Patients with Stable Coronary Artery Disease) study showed that rivaroxaban monotherapy was non-inferior to DAT in terms of both bleeding and ischemic outcomes. The EPIC-CAD (Edoxaban versus Edoxaban with Antiplatelet Agent in Patients with Atrial Fibrillation and Chronic Stable Coronary Artery Disease) trial further extended this evidence, indicating that edoxaban monotherapy reduced the risk of net adverse clinical events (NACE)-a composite of death, myocardial infarction, stroke, systemic embolism, unplanned urgent revascularization, and major or clinically relevant nonmajor bleeding-compared to DAT. Recently, the ADAPT AF-DES (Appropriate Duration of Antiplatelet and Thrombotic Strategy after 12 Months in Patients with Atrial Fibrillation Treated with Drug-Eluting Stents) trial demonstrated that DOAC monotherapy was non-inferior, and even superior, to combination therapy with a DOAC and clopidogrel regarding NACE reduction in patients with AF and stable CAD following PCI. However, these studies have primarily focused on patients with stable CAD who inherently have a lower ischemic risk. Despite limited evidence supporting DOAC monotherapy as a maintenance strategy for acute myocardial infarction (AMI) patients, recent guidelines have also recommended this approach after 1 year (Class I) or 6 months (Class IIB) following PCI in AMI setting. Furthermore, in real-world data, the DAT remained effective in reducing ischemic events without increasing the risk of bleeding compared with DOAC monotherapy. Additionally, DOAC monotherapy showed a lower risk of NACE at 3 years, but was not significantly effective at 1 year after PCI. To address this critical evidence gap in clinical practice, we have developed the Heart-team for Evidence-based Revascularization: Abbreviated Antithrombotic Therapy After Percutaneous Coronary Intervention in Patients with Atrial Fibrillation and Acute Myocardial Infarction (HERO-AF-AMI). This study aims to evaluate the impact of DOAC monotherapy compared to DAT (DOAC plus clopidogrel) in patients with AF and AMI undergoing PCI.
Interventions
DRUGDAT (DOAC+clopidogrel)
Patients allocated to the DAT group receive either apixaban 5 mg twice daily, edoxaban 60 mg once daily, or rivaroxaban 15 mg once daily with clopidogrel 75 mg once daily.
DRUGDOAC monotherapy
Patients allocated to the DOAC monotherapy group receive either apixaban 5 mg twice daily, edoxaban 60 mg once daily, or rivaroxaban 20 mg once daily.
Sponsors
Chonnam National University Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Intervention model description
A prospective, multi-center, open label, randomized controlled, superiority trial to compare clinical outcomes between direct oral anticoagulants (DOAC) monotherapy versus DOAC and clopidogrel as maintenance strategies in AF and AMI patients after percutaneous coronary intervention (PCI)
Eligibility
Sex/Gender
ALL
Age
19 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Patients aged 19 years old 2. Patients with AF and CHA2DS2-VA score ≥2. 3. ST-segment elevation myocardial infarction (STEMI) or Non-ST-segment elevation myocardial infarction (NSTEMI) * STEMI: ST-segment elevation ≥0.1 mV in ≥2 contiguous leads or documented newly developed left bundle-branch block.12 * NSTEMI: NSTEMI is defined as a combination of criteria with mandated elevation of a cardiac biomarker, preferably high-sensitive cardiac troponin with at least one value above 99th percentile of the upper reference limit and at least one of the following:12 1. Symptoms of ischemia. 2. New or presumed new significant ST-T wave changes 3. Development of pathological Q waves on electrocardiography. 4. Imaging evidence of new or presumed new loss of viable myocardium or regional wall motion abnormality. 5. Intracoronary thrombus detected on angiography. 4. Patients underwent PCI for AMI (STEMI or NSTEMI) at least 6 months before enrollment.
Exclusion criteria
1. Patients contraindicated for use of DOACs or clopidogrel 2. Mechanical prosthetic valve or moderate-to-severe mitral stenosis requiring vitamin K antagonist 3. Planned cardiac surgery within 1 year after randomization 4. Patients with severe thrombocytopenia or coagulopathy 5. Liver cirrhosis or severe hepatic dysfunction 6. Advanced chronic kidney disease (creatinine clearance \<15 ml/min/1.73 m2) or on dialysis 7. Prior history of intracranial hemorrhage 8. Coexisting conditions related to high risk of life-threatening bleeding 9. Pregnancy or breast feeding 10. Non-cardiac co-morbid conditions are present with life expectancy \<1 year or that may result in protocol non-compliance (per site investigator's medical judgment) 11. Unwillingness or inability to comply with the procedures described in this protocol.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| NACE (net adverse clinical events) | 1 year after the last patient enrollment | a composite of death, non-fatal MI, stroke, systemic embolization, unplanned revascularization, stent thrombosis, major or clinically relevant non-major bleeding by ISTH |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Rate of major bleeding by ISTH | 1 year after the last patient enrollment | major bleeding events by ISTH definition |
| Rate of MACCE (major adverse cardiac and cerebrovascular event) | 1 year after the last patient enrollment | a composite of cardiovascular death, non-fatal MI, ischemic stroke, systemic embolization, unplanned revascularization, and stent thrombosis |
| All-cause death | 1 year after the last patient enrollment | all-cause death |
| Cardiovascular death | 1 year after the last patient enrollment | cardiovascular death |
| Rate of non-fatal MI | 1 year after the last patient enrollment | non-fatal MI, defined by Fourth Universal definition of MI |
| Rate of ischemic stroke | 1 year after the last patient enrollment | ischemic stroke |
| Rate of systemic embolization | 1 year after the last patient enrollment | systemic embolization |
| Rate of unplanned revascularization | 1 year after the last patient enrollment | unplanned revascularization (clinically-driven) |
| Rate of definite stent thrombosis | 1 year after the last patient enrollment | definite stent thrombosis, defined by Academic Research Consortium (ARC) II consensus |
| Rate of cardiovascular death or non-fatal MI | 1 year after the last patient enrollment | a composite of cardiovascular death or non-fatal MI |
| Rate of all-cause death, non-fatal MI, stroke, systemic embolization, stent thrombosis, or ISTH major bleeding | 1 year after the last patient enrollment | a composite of all-cause death, non-fatal MI, stroke, systemic embolization, stent thrombosis, or ISTH major bleeding |
| Rate of major or clinically relevant non-major bleeding by ISTH | 1 year after the last patient enrollment | major or clinically relevant non-major bleeding by ISTH |
| Rate of fatal bleeding by ISTH | 1 year after the last patient enrollment | fatal bleeding by ISTH |
| Rate of clinically relevant non-major bleeding by ISTH | 1 year after the last patient enrollment | clinically relevant non-major bleeding by ISTH |
| Rate of any bleeding by ISTH | 1 year after the last patient enrollment | any bleeding by ISTH |
Countries
South Korea
Contacts
CONTACTSeung Hun Lee, MD, PhD
CONTACTJoon Ho Ahn, MD, PhD
STUDY_CHAIRYoung Joon Hong, MD, PhD
Chonnam National University
Outcome results
None listed