What is the Optimal Antithrombotic Strategy in Patients With Atrial Fibrillation Undergoing PCI? (WOEST-3)

St. Antonius Hospital

Status and phase: Enrolling; Phase 4

Conditions: Coronary Artery Disease; Embolism; NSTEMI - Non-ST Segment Elevation MI; Atrial Flutter; Atrial Fibrillation; Stroke; Acute Coronary Syndrome; Myocardial Infarction; STEMI - ST Elevation Myocardial Infarction; Stent Thrombosis; Bleeding

Treatments: Drug: Guideline-directed therapy; Drug: 30-day DAPT

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT04436978

NL81102.100.22

2022-001298-30 (EudraCT Number)

Details and patient eligibility

About

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.

Enrollment: 2,000 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Patients ≥ 18 years
2. Undergoing successful PCI (either ACS or elective PCI)
3. History of or newly diagnosed (<72 hours after PCI/ACS) atrial fibrillation or flutter with a long-term (≥ 1 year) indication for OAC

Exclusion criteria

1. Contra indication to edoxaban, aspirin or all P2Y12 inhibitors
2. Current indication for OAC besides atrial fibrillation/flutter (e.g. venous thromboembolism)
3. <12 months after any stroke
4. CHADSVASc score ≥7
5. Moderate to severe mitral valve stenosis (AVA ≤1.5 cm2)
6. Mechanical heart valve prosthesis
7. Intracardiac thrombus or apical aneurysm requiring OAC
8. Poor LV function (LVEF <30%) with proven slow-flow
9. History of intracranial haemorrhage
10. Active bleeding on randomization
11. History of intraocular, spinal, retroperitoneal, or traumatic intra-articular bleeding, unless the causative factor has been permanently resolved
12. Recent (<1 month) gastrointestinal haemorrhage, unless the causative factor has been permanently resolved.
13. Known coagulopathy
14. Severe anaemia requiring blood transfusion or thrombocytopenia <50 × 109/L
15. BMI >40 or bariatric surgery
16. Kidney failure (eGFR <15)
17. Active liver disease (ALT, ASP, AP >3x ULN or active hepatitis A, B or C)
18. Active malignancy excluding non-melanoma skin cancer
19. Life expectancy <1 year
20. Pregnancy or breast-feeding women

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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2,000 participants in 2 patient groups

First month DAPT

Active Comparator group

Description:

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.

Treatment:

Drug: 30-day DAPT

Guideline-directed therapy

Active Comparator group

Description:

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.

Treatment:

Drug: Guideline-directed therapy