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.

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

Will individual participant data be available? Yes

What data in particular will be shared? Individual participant data that underlie the results reported in this article, after deidentification (text, tables, figures, and appendices).

What other documents will be available? Study Protocol, informed consent form, clinical study report

When will data be available (start and end dates)? Within 1 year following article publication. End date to be determined.

With whom? Researchers who provide a methodologically sound proposal.

For what types of analyses? To achieve aims in the approved proposal.

By what mechanism will data be made available? Proposals should be directed to as.verburg@antoniusziekenhuis.nl. To gain access, data requestors will need to sign a data access agreement.

Within 1 year following article publication. End date to be determined.

Researchers who provide a methodologically sound proposal.