Bleeding, Cardiac Event, Coronary Artery Disease, Peripheral Artery Disease
Conditions
Keywords
Anti-platelet therapy, anticoagulant therapy
Brief summary
The study aims to conduct a randomized controlled trial among adults aged 19 years or older who have experienced acute myocardial infarction at least one year prior, or who have other comorbidities such as peripheral arterial disease or multiple cardiovascular diseases, and have consented to participate in the study. Participants will be randomly assigned to either a group that maintains antiplatelet therapy with aspirin and clopidogrel or clopidogrel alone, or a group that maintains combined antiplatelet and anticoagulant therapy with aspirin and low-dose rivaroxaban in a 1:1 ratio. The study aims to demonstrate that maintaining clopidogrel-based antiplatelet therapy is not clinically inferior to maintaining combined therapy with aspirin and low-dose rivaroxaban.
Detailed description
Rupture of atherosclerotic plaques and resulting thrombotic or embolic events can lead to myocardial infarction, stroke, and death. Particularly after vascular interventions such as percutaneous coronary intervention, stent implantation, or peripheral vascular interventions, it takes more than a year for the damaged endothelial cells to heal completely, leading to frequent thrombotic complications. In addition, clinically undiagnosed atrial fibrillation, stroke caused by thrombosis formation due to venous damage, myocardial infarction, deep vein thrombosis, and pulmonary embolism may occur. Therefore, drug therapy to prevent thrombosis is necessary for these patients, and many studies have been conducted to determine the optimal treatment. Dual antiplatelet therapy (DAPT) with aspirin and clopidogrel is essential for treating patients after percutaneous coronary intervention (PCI). DAPT can minimize ischemic events not only in stent lesions but also in non-reperfused lesions of the coronary artery. However, DAPT increases the risk of bleeding, so a treatment strategy is needed to minimize ischemic events while reducing the risk of bleeding by using dual antiplatelet therapy for a short time after the procedure, administering antiplatelet drugs differently depending on the bleeding risk. In particular, in patients at high risk of bleeding (HBR), the side effects of bleeding due to long-term antiplatelet therapy are closely related to long-term survival, making this issue even more important. Compared to traditional aspirin use, the use of clopidogrel has been reported to reduce mortality, myocardial infarction, stroke, and hospitalization due to acute coronary artery disease while reducing bleeding complications. In addition, a study has reported that combining low-dose anticoagulants with aspirin as a thromboprophylactic agent for stable atherosclerotic patients who were previously treated only with antiplatelet drugs reduces mortality and has superior effects on the prevention of myocardial infarction and stroke compared to aspirin alone. Aspirin and low-dose rivaroxaban combination therapy has been approved for use in patients with multivessel CAD who are over 65 years of age and have experienced acute myocardial infarction for more than one year, as well as patients with peripheral arterial disease (PAD) (history of PTA or bypass, history of foot/leg amputation, intermittent claudication with ABI \<0.9, or over 50% stenosis in peripheral arteries, or over 50% stenosis in coronary arteries or previous coronary stent implantation) who have one of the two conditions: a history of acute myocardial infarction for over one year or multivessel CAD. Ultimately, studies comparing clopidogrel and low-dose rivaroxaban and aspirin combination therapy in similar patient populations have shown the superiority of each treatment strategy, but no studies have compared the two treatment strategies. If clopidogrel monotherapy is more convenient to take, has better compliance, and is not less effective than low-dose rivaroxaban and aspirin combination therapy, it may be considered as a more convenient treatment strategy for many patients.
Interventions
DRUGAspirin and low-dose rivaroxaban
Combination of aspirin and low-dose rivaroxaban
DRUGClopidogrel with or without aspirin
Clopidogrel-based SAPT or DAPT at the clinician's discretion
Sponsors
Seoul National University Bundang Hospital
Korea University Guro Hospital
Korea University Ansan Hospital
Korea University Anam Hospital
Chungnam National University Sejong Hospital
National Health Insurance Service Ilsan Hospital
Ewha Womans University Seoul Hospital
Konyang University Hospital
Seoul National University Hospital
KangWon National University Hospital
Sejong General Hospital
Inha University Hospital
Severance Hospital
Myongji Hospital
Chonnam National University Hospital
Chungnam National University Hospital
Jeju National University Hospital
Kwangju christian hospital
Soonchunhyang University Hospital
Wonju Severance Christian Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Intervention model description
Parallel assignment
Eligibility
Sex/Gender
ALL
Age
19 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients over 65 years of age who have experienced acute myocardial infarction and have multivessel coronary artery disease (CAD) that has been present for over one year * Patients who have peripheral arterial disease (history of PTA or bypass, history of foot/leg amputation, intermittent claudication with ABI \<0.9 or over 50% stenosis in peripheral arteries, or over 50% stenosis in coronary arteries or previous coronary stent implantation) and have a history of acute myocardial infarction for over one year or have one of the two conditions: multivessel CAD. * Subject is able to verbally confirm understandings of risks, benefits and treatment, and he/she or his/her legally authorized representative provides written informed consent prior to study
Exclusion criteria
* History of serious hypersensitivity reactions to aspirin, clopidogrel, or prasugrel. * Patients with coagulation disorders or liver diseases related to coagulation, as well as patients with moderate (Child Pugh B) and severe (Child Pugh C) liver dysfunction. * Severe renal impairment with a creatinine clearance less than 15 mL/min. * Patients who require long-term combination therapy with other anticoagulants such as unfractionated heparin (UFH), low molecular weight heparin (enoxaparin, dalteparin, etc.), heparinoids (fondaparinux, etc.), oral anticoagulants (warfarin, apixaban, dabigatran, etc.). * In cases of active clinical bleeding at the time of study registration. * Patients who require discontinuation of antiplatelet therapy for more than 3 months due to surgery or procedure * Individuals with an expected lifespan of less than 3 years due to reasons other than cardiovascular disease. * Concomitant use of the following contraindicated drugs: other P2Y12 inhibitors (prasugrel or ticagrelor); cytochrome P450 2C19 inhibitors (fluoxetine, fluvoxamine, or voriconazole); probenecid; high-dose methotrexate (≥15 mg/week); lithium. * Pregnant or breastfeeding women. * Inability to provide informed consent
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Patient oriented cardiac event | 36 months | All-cause death, any myocardial infarction, any stroke, any revascularization (coronary or peripheral disease), acute limb ischemia (including all major vascular amputations), any acute thromboembolism, and BARC classification ≥ 2 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Composite of MI, stroke or CV death in CAD and PAD group | 36 months | Myocardial infarction, stroke or cardiovascular death measured by percent of all participants with adverse events |
| Patency of target lesion in PAD intervention group | 36 months | Measured by percent of participants undergone repeat PTA to the previous lesion |
| Composite of major thrombotic events | 36 months | Cardiovascular death, MI, ischemic stroke, stent thrombosis or acute limb ischemia, venous thromboembolism (Deep vein thrombosis or pulmonary embolism) |
| Composite of MI, stroke or CV death in CAD only group | 36 months | Myocardial infarction, stroke or cardiovascular death measured by percent of coronary disease participants with adverse events |
| Patient oriented cardiac event in PAD only group | 36 months | All-cause death, any myocardial infarction, any stroke, any revascularization (coronary or peripheral disease), acute limb ischemia (including all major vascular amputations), any acute thromboembolism, and BARC classification ≥ 2 |
| Composite of MI, stroke or CV death | 36 months | Myocardial infarction, stroke or cardiovascular death measured by percent of participants with adverse events |
| Patient oriented cardiac event in CAD only group | 36 months | All-cause death, any myocardial infarction, any stroke, any revascularization (coronary or peripheral disease), acute limb ischemia (including all major vascular amputations), any acute thromboembolism, and BARC classification ≥ 2 |
Countries
South Korea
Contacts
CONTACTJu Seung Kwun, M.D
CONTACTChang-Hwan Yoon, M.D Ph.D
PRINCIPAL_INVESTIGATORIn-Ho Chae, M.D Ph.D
Seoul National University Bundang Hospital
Outcome results
None listed