Major adverse cardiovascular and bleeding outcomes in paroxysmal vs. non-paroxysmal atrial fibrillation: an individual patient-level data analysis of a large cohort of patients from the COMBINE-AF

Abstract Background: We performed an individual patient data analysis of COMBINE AF to assess differences in 14 clinically relevant outcomes between patients with paroxysmal (PAF) vs. non-PAF. Methods: Cox-proportional-hazards models stratified by trial and adjusted for CHA2DS2-VASc elements were constructed. Sensitivity analyses were performed across subgroups. Results: Among 71,466 patients with AF, 16,609 (23 %) had PAF. The overall follow-up period was 157,225 patient-years (median 2.2 years). Compared with non-PAF patients, PAF patients were more likely to be women (43 % vs 35 %), have prior coronary artery disease (35 % vs 31 %), and use aspirin (41 % vs 32 %), but were less likely to be Asian (12 % vs 15 %) or have CHA₂DS₂-VASc ≥4 (59 % vs 60 %) (all p<0.01). In adjusted analyses, PAF was associated with a lower risk of stroke/systemic embolic event (HR, 0.81; 95 % CI, 0.73–0.90; p<0.001) and all-cause death (HR, 0.81; 95 % CI, 0.75–0.86; p<0.001), but higher risk of major or clinically relevant non-major bleeding (HR, 1.07; 95 % CI, 1.02–1.13; p=0.005). Risk of myocardial infarction was numerically higher in PAF (HR, 1.15; 95 % CI, 1.00–1.32; p=0.057). Major bleeding risk was similar between groups (HR, 1.04; 95 % CI, 0.96–1.12; p=0.36). Findings were consistent across subgroups, trials, anticoagulant types, and sensitivity analyses. Conclusions: Compared to non-PAF, adjusted risks in PAF patients were lower for stroke/systemic embolic event and all-cause death, and higher for major or clinically relevant non-major bleeding and myocardial infarction.These findings highlight clinically important differences in outcomes by AF type that may have clinical applications for AF patients.