1-month versus 12-month dual antithrombotic therapy after percutaneous coronary intervention in patients with atrial fibrillation (OPTIMA-AF): a multicentre, open-label, hybrid non-inferiority and superiority, randomised, controlled trial.

Abstract (English)

BACKGROUND: The optimal duration of dual antithrombotic therapy after percutaneous coronary intervention (PCI) in patients with atrial fibrillation remains uncertain. We aimed to compare the efficacy and safety of 1-month versus 12-month dual antithrombotic therapy in this population. METHODS: OPTIMA-AF was an active-control, randomised, hybrid non-inferiority and superiority trial in which patients with atrial fibrillation undergoing PCI with intravascular imaging guidance were randomly assigned (1:1) to receive 1-month dual antithrombotic therapy (direct oral anticoagulant [DOAC] plus P2Y12 inhibitor) followed by DOAC monotherapy or 12-month dual therapy followed by DOAC monotherapy, across 75 sites in Japan. Eligible patients were aged 20 years or older with non-valvular atrial fibrillation, a CHADS₂ score of 1 or higher, undergoing PCI for native coronary lesions for chronic coronary syndrome or unstable angina, with planned post-PCI treatment with a DOAC. Randomisation used web-based central allocation stratified by trial centre. Investigators and patients were unmasked; clinical events were adjudicated by an independent committee masked to treatment. The primary efficacy endpoint was a composite of all-cause death or thromboembolic events at 12 months; the primary safety endpoint was major or clinically relevant non-major bleeding at 12 months. The trial used a fixed-sequence testing strategy of non-inferiority for efficacy, superiority for safety, and superiority for efficacy. Analyses used the full analysis set including all patients who underwent PCI, were randomly assigned to treatment, received at least one dose of study drugs, and met prespecified analysis-set criteria. This trial is registered with the Japan Registry of Clinical Trials (jRCTs051190053), and is complete. FINDINGS: From Oct 7, 2019, to Sept 3, 2024, 1101 patients were assessed for eligibility; 1088 were randomly assigned to treatment and 1079 were included in the full analysis set (1-month dual therapy n=542; 12-month dual therapy n=537). Median age was 76 years (IQR 70-81). 225 (21%) of 1079 patients were female and 854 (79%) were male. Median CHADS₂ score was 2 (IQR 2-3). Median follow-up was 540 days (IQR 517-559). The primary efficacy endpoint occurred in 29 patients in the 1-month dual therapy group and 23 patients in the 12-month dual therapy group (Kaplan-Meier estimate 5·4% vs 4·3%; absolute difference 1·1 percentage points [95% CI -1·5 to 3·6]; hazard ratio [HR] 1·25 [95% CI 0·73-2·17]). The primary safety endpoint occurred in 24 patients versus 47 patients (Kaplan-Meier estimate 4·5% vs 8·8%; absolute difference -4·4 percentage points [95% CI -7·3 to -1·4]; HR 0·50 [95% CI 0·30-0·81]; p=0·0041 for superiority). INTERPRETATION: Among patients with atrial fibrillation and predominantly chronic coronary syndrome undergoing PCI with intravascular imaging guidance, 1-month dual antithrombotic therapy followed by DOAC monotherapy was non-inferior to 12-month therapy for death or thromboembolic events and reduced major or clinically relevant non-major bleeding at 12 months, suggesting an overall favourable net clinical profile. Efficacy findings should be interpreted with appropriate caution in light of the lower-than-anticipated event rates and fixed absolute non-inferiority margin. FUNDING: Abbott Medical Japan. TRANSLATIONS: For the Japanese translation of the abstract see Supplementary Materials section.