Temporary omission of oral anticoagulation in atrial fibrillation patients undergoing percutaneous coronary intervention: rationale and design of the WOEST-3 randomised trial

Abstract

The optimal antithrombotic management of atrial fibrillation (AF) patients who require oral anticoagulation (OAC) undergoing percutaneous coronary intervention (PCI) remains unclear. Current guidelines recommend dual antithrombotic therapy (DAT; OAC plus P2Y₁₂ inhibitor - preferably clopidogrel) after a short course of triple antithrombotic therapy (TAT; DAT plus aspirin). Although DAT reduces bleeding risk compared to TAT, this is counterbalanced by an increase in ischaemic events. Aspirin provides early ischaemic benefit, but TAT is associated with an increased haemorrhagic burden; therefore, we propose a 30-day dual antiplatelet therapy (DAPT; aspirin plus P2Y₁₂ inhibitor) strategy post-PCI, temporarily omitting OAC. The study aims to compare bleeding and ischaemic risk between a 30-day DAPT strategy following PCI and a guideline-directed therapy in AF patients requiring OAC. WOEST-3 (ClinicalTrials.gov: NCT04436978) is an investigator-initiated, international, open-label, randomised controlled trial (RCT). AF patients requiring OAC who have undergone successful PCI will be randomised within 72 hours after PCI to guideline-directed therapy (edoxaban plus P2Y₁₂ inhibitor plus limited duration of aspirin) or a 30-day DAPT strategy (P2Y₁₂ inhibitor plus aspirin, immediately discontinuing OAC) followed by DAT (edoxaban plus P2Y₁₂ inhibitor). With a sample size of 2,000 patients, this trial is powered to assess both superiority for major or clinically relevant non-major bleeding and non-inferiority for a composite of all-cause death, myocardial infarction, stroke, systemic embolism or stent thrombosis. In summary, the WOEST-3 trial is the first RCT temporarily omitting OAC in AF patients, comparing a 30-day DAPT strategy with guideline-directed therapy post-PCI to reduce bleeding events without hampering efficacy.

Figure 1. Study design and outcome measures.

AF patients with a successful PCI will be randomised in a 1:1 ratio to DAPT (aspirin+P2Y₁₂ inhibitor) versus standard therapy (edoxaban+P2Y₁₂ inhibitor+aspirin up to 30 days) in the first month after PCI, followed by DAT (edoxaban+P2Y₁₂ inhibitor). AF: atrial fibrillation; CRNM: clinically relevant non-major; DAPT: dual antiplatelet therapy; DAT: dual antithrombotic therapy; ISTH: International Society on Thrombosis and Haemostasis; MI: myocardial infarction; PCI: percutaneous coronary intervention; SE: systemic embolism; ST: stent thrombosis