What is the Optimal Antithrombotic Strategy in Patients With Atrial Fibrillation Having Acute Coronary Syndrome or Undergoing Percutaneous Coronary Intervention?
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 入组人数
- 2,000
- 试验地点
- 20
- 主要终点
- Primary efficacy endpoint
研究概览
简要总结
The optimal antithrombotic management in patients with coronary artery disease (CAD) and concomitant atrial fibrillation (AF) is unknown. AF patients are treated with oral anticoagulation (OAC) to prevent ischemic stroke and systemic embolism and patients undergoing percutaneous coronary intervention (PCI) are treated with dual antiplatelet therapy (DAPT), i.e. aspirin plus P2Y12 inhibitor, to prevent stent thrombosis (ST) and myocardial infarction (MI). Patients with AF undergoing PCI were traditionally treated with triple antithrombotic therapy (TAT, i.e. OAC plus aspirin and P2Y12 inhibitor) to prevent ischemic complications. However, TAT doubles or even triples the risk of major bleeding complications. More recently, several clinical studies demonstrated that omitting aspirin, a strategy known as dual antithrombotic therapy (DAT) is safer compared to TAT with comparable efficacy.
However, pooled evidence from recent meta-analyses suggests that patients treated with DAT are at increased risk of MI and ST. Insights from the AUGUSTUS trial showed that aspirin added to OAC and clopidogrel for 30 days, but not thereafter, resulted in fewer severe ischemic events. This finding emphasizes the relevance of early aspirin administration on ischemic benefit, also reflected in the current ESC guideline. However, because we consider the bleeding risk of TAT unacceptably high, we propose to use a short course of DAPT (omitting OAC for 1 month). There is evidence from the BRIDGE study that a short period of omitting OAC is safe in patients with AF. In this study, these patients are treated with DAPT, which also prevents stroke, albeit not as effective as OAC. This temporary interruption of OAC will allow aspirin treatment in the first month post-PCI where the risk of both bleeding and stent thrombosis is greatest.
The WOEST 3 trial is a multicentre, open-label, randomised controlled trial investigating the safety and efficacy of one month DAPT compared to guideline-directed therapy consisting of OAC and P2Y12 inhibitor combined with aspirin up to 30 days. We hypothesise that the use of short course DAPT is superior in bleeding and non-inferior in preventing ischemic events. The primary safety endpoint is major or clinically relevant non-major bleeding as defined by the ISTH at 6 weeks after PCI. The primary efficacy endpoint is a composite of all-cause death, myocardial infarction, stroke, systemic embolism, or stent thrombosis at 6 weeks after PCI.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Single (Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients ≥ 18 years
- •Undergoing successful PCI (either ACS or elective PCI)
- •History of or newly diagnosed (<72 hours after PCI/ACS) atrial fibrillation or flutter with a long-term (≥ 1 year) indication for OAC
排除标准
- •Contra indication to edoxaban, aspirin or all P2Y12 inhibitors
- •Current indication for OAC besides atrial fibrillation/flutter (e.g. venous thromboembolism)
- •<12 months after any stroke
- •CHADSVASc score ≥7
- •Moderate to severe mitral valve stenosis (AVA ≤1.5 cm2)
- •Mechanical heart valve prosthesis
- •Intracardiac thrombus or apical aneurysm requiring OAC
- •Poor LV function (LVEF <30%) with proven slow-flow
- •History of intracranial haemorrhage
- •Active bleeding on randomization
- •History of intraocular, spinal, retroperitoneal, or traumatic intra-articular bleeding, unless the causative factor has been permanently resolved
- •Recent (<1 month) gastrointestinal haemorrhage, unless the causative factor has been permanently resolved.
- •Known coagulopathy
- •Severe anaemia requiring blood transfusion or thrombocytopenia <50 × 109/L
- •BMI >40 or bariatric surgery
- •Kidney failure (eGFR <15)
- •Active liver disease (ALT, ASP, AP >3x ULN or active hepatitis A, B or C)
- •Active malignancy excluding non-melanoma skin cancer
- •Life expectancy <1 year
- •Pregnancy or breast-feeding women
研究组 & 干预措施
First month DAPT
30-day DAPT (aspirin + P2Y12 inhibitor). After 30 days all patients will be treated with edoxaban and P2Y12 inhibitor.
Selection of P2Y12 inhibitor is at the discretion of the treating physician, depending on both bleeding and ischemic risk. Dosage of aspirin and P2Y12 inhibitor is according to local guidelines.
NOAC of choice will be edoxaban. Patients will be treated with the recommended dose of 60mg once daily or the reduced dose of 30mg once daily.
干预措施: 30-day DAPT (Drug)
Guideline-directed therapy
Standard guideline-directed therapy (edoxaban + P2Y12 inhibitor, aspirin limited to in-hospital use or up to 30 days in selected high-risk patients). After 30 days all patients will be treated with edoxaban and P2Y12 inhibitor.
Selection of P2Y12 inhibitor is at the discretion of the treating physician, depending on both bleeding and ischemic risk. Dosage of aspirin and P2Y12 inhibitor is according to local guidelines.
NOAC of choice will be edoxaban. Patients will be treated with the recommended dose of 60mg once daily or the reduced dose of 30mg once daily.
干预措施: Guideline-directed therapy (Drug)
结局指标
主要结局
Primary efficacy endpoint
时间窗: 6 weeks
Composite of all-cause death, myocardial infarction, stroke, systemic embolism, or stent thrombosis
Primary safety endpoint
时间窗: 6 weeks
Major or clinically relevant non-major bleeding as defined by the International Society of Thrombosis and Haemostasis
次要结局
- Clinical symptom severity(6 weeks, 3 months, 6 months)
- Bleeding complications(6 months)
- Thrombotic complications(6 months)
- Net clinical benefit(6 weeks, 3 months, 6 months)
- All-cause death(6 weeks, 3 months, 6 months)
- Myocardial infarction(6 weeks, 3 months, 6 months)
- Stroke(6 weeks, 3 months, 6 months)
- Systemic embolism(6 weeks, 3 months, 6 months)
- Stent thrombosis(6 weeks, 3 months, 6 months)
- Major bleeding(6 weeks, 3 months, 6 months)
- Clinically relevant non-major bleeding(6 weeks, 3 months, 6 months)
研究者
Jurriën M. ten Berg, MD, PhD
Professor dr.
St. Antonius Hospital