What is the Optimal Antithrombotic Strategy in Patients Presenting With Acute Coronary Syndrome Having Atrial Fibrillation With Indication for Anticoagulants?

• Status: Not yet recruiting
• Trial end date: 2027-12-01
• Target enrollment: 0
• Participant gender: All

Summary

The optimal antithrombotic management in patients with coronary artery disease (CAD) and concomitant atrial fibrillation (AF) is unknown. Patients with AF are treated with oral anticoagulation (OAC) to prevent ischemic stroke and systemic embolism and patients with acute coronary syndrome (ACS) or those who undergo percutaneous coronary intervention (PCI) are treated with dual antiplatelet therapy (DAPT), i.e. aspirin plus P2Y12 inhibitor (clopidogrel), to prevent stent thrombosis (ST) and myocardial infarction (MI). Patients with AF undergoing PCI were traditionally treated with triple antithrombotic therapy (TAT, i.e. oral anticoagulation (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 myocardial infarction (MI), stent thrombosis (ST) and even cardiovascular (CV) death. 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 (drop the 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 that also prevents stroke, albeit not as effective as OAC. Thus, by omitting OAC in the first month, we make room for aspirin use for optimal prevention of myocardial infarction or stent thrombosis in the first month after ACS or PCI.

The WOEST 3 trial is a multicentre, open-label, randomised controlled trial to investigate the safety and efficacy of one month DAPT compared to standard 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, secondary, non-inferior in preventing ischemic events. The primary endpoint is clinically relevant bleeding (according to the International Society of Thrombosis and Haemostasis definition) after one month. Secondary endpoints include a composite of CV death, MI, ischemic stroke, ST, and systemic embolism after one month, and one year follow-up.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: St. Antonius Hospital

Criteria

Inclusion Criteria:

1. Patients ≥ 18 years

2. Presenting with ACS with elevated cardiac markers (CK/CK-MB, troponin) or undergoing PCI

3. Documented or newly diagnosed non-valvular AF (<72 hours after ACS) treated with OAC or intention to treat >1 year

Exclusion Criteria:

1. History of ischemic stroke

2. Mechanical prosthetic heart valve

3. <3 months after venous thromboembolism

4. CHA2DS2-VASc >5

5. Intracardiac thrombus

6. Rheumatic valve disease

7. Moderate/severe mitral valve stenosis

8. Conditions other than atrial fibrillation that require anticoagulation for which direct oral anticoagulants will not be sufficient (e.g. prosthetic mechanical heart valve, antiphospholipid syndrome)

9. History of known coagulopathy

10. Estimated Glomerular Filtration Rate < 15 mL/min/1.73m^2