Dual antithrombotic therapy with dabigatran and ticagrelor in patients with acute coronary syndrome and non-valvular atrial fibrillation undergoing percutaneous coronary intervention (ADONIS-PCI): protocol for a randomized controlled pilot trial.

INTRODUCTION: Patients with atrial fibrillation (AF) presenting with acute coronary syndrome (ACS) and undergoing percutaneous coronary intervention (PCI) require protection against both cardioembolic and coronary thrombotic events, while facing a substantial bleeding risk. Oral anticoagulation (OAC) reduces the risk of stroke and systemic embolism but does not adequately address stent-related thrombotic risk. Conversely, dual antiplatelet therapy reduces recurrent coronary ischemic events and stent thrombosis but is insufficient for AF-related thromboembolism. Current antithrombotic strategies therefore rely on abbreviated triple antithrombotic therapy followed by dual antithrombotic therapy; however, the optimal P2Y12 inhibitor and dosing strategy in patients with AF and ACS treated with PCI remain uncertain.

MATERIAL AND METHODS: ADONIS-PCI is an investigator-initiated, prospective, multicenter, randomized, open-label, blindedendpoint, non-inferiority trial (NCT04695106; EUCT number: 2024-515056-20-00). Consecutive patients with nonvalvular AF hospitalized for ACS and successfully treated with PCI are randomized within 120 hours after PCI in a 1:1 ratio to receive either dual antithrombotic therapy with dabigatran (150 mg twice daily or 110 mg twice daily) plus ticagrelor (90 mg twice daily for 1 month, followed by 60 mg twice daily up to 12 months), or standard antithrombotic therapy according to contemporary guideline-based care, consisting of dabigatran (150 mg twice daily or 110 mg twice daily), clopidogrel (75 mg once daily), and aspirin (75 mg once daily), followed by dual therapy according to bleeding and ischemic risk. Study treatment is continued for 12 months. The primary endpoint is the first International Society on Thrombosis and Haemostasis (ISTH) major or clinically relevant non-major bleeding event in a time-to-event analysis. The main secondary endpoint is a composite of thromboembolic events (myocardial infarction, stroke, or systemic embolism), death, or unplanned revascularization (PCI or coronary artery bypass grafting) at 12 months. ADONIS-PCI will evaluate whether a dabigatran-based aspirin-free strategy using ticagrelor dose de-escalation can preserve ischemic protection while reducing the bleeding burden in patients with AF and ACS undergoing PCI.

CONCLUSIONS: ADONIS-PCI is among the first randomized evaluations of a reduced-dose long-term ticagrelor strategy combined with dabigatran in patients with AF and ACS undergoing PCI. The trial addresses an important evidence gap in the selection and dosing of P2Y12 inhibition when aspirin is discontinued early in this high-risk population.