Patient characteristics and real-world outcomes among atrial fibrillation patients treated with direct oral anticoagulants (DOACs) and vitamin K antagonists (VKAs) in Spain

Abstract Background In Spain, Vitamin K Antagonists (VKAs) remain the first-line therapy for stroke prevention in atrial fibrillation (AF) patients, as prescribing direct oral anticoagulants (DOACs) requires prior authorization to fulfill reimbursement criteria. Despite these reimbursement restrictions, a documented increase in DOAC use for stroke prevention in AF patients has been observed from 2013-2020. Real-world evidence is essential to gain further insights into the clinical outcomes and usage patterns of DOACs and VKAs in AF management. Purpose The goal of this study is to evaluate the effectiveness and safety of DOACs vs. VKAs for stroke prevention in AF patients in routine clinical practice in Spain, including incidence rates of ischemic stroke (IS), systemic embolism (SE), major bleeding (MB), and all-cause mortality. Methods This retrospective observational cohort analysis used Spanish BIG-PAC data from 01/01/2017-31/12/2023, including adult nonvalvular AF patients initially prescribed a DOAC (edoxaban, apixaban, dabigatran, rivaroxaban) or a VKA (index date=first DOAC/VKA prescription). Patients with deep vein thrombosis, pulmonary embolism, mechanical heart valves within 12 months, or hip/knee replacements within 6 weeks before index were excluded. DOAC and VKA cohorts based on index treatment were identified. Effectiveness, safety, and all-cause mortality were compared between cohorts using inverse probability of treatment weighting (IPTW) to adjust for confounding, with hazard ratios (HR) and 95% confidence intervals (CI) calculated to assess outcomes. Sensitivity analyses censored data at 12 months. Results A total of 15,348 patients were included (DOACs, n=8,264; VKAs, n=7,084). After applying IPTW, patient characteristics were balanced across groups. DOACs showed significantly lower risk of MB compared to VKAs (HR [95% CI]: 0.47 [0.42-0.53]) and lower all-cause mortality (HR [95% CI]: 0.63 [0.58-0.68]). Similar results were seen for MB when censored at 12 months (Table 1). Additional analyses compared clinical outcomes between the 4 DOAC cohorts. Compared with edoxaban, dabigatran had a higher risk of IS/SE (HR [95% CI]: 2.12 [1.44–3.14]) and all-cause mortality (HR [95% CI]: 1.39 [1.02-1.89]) and apixaban had a higher risk of IS/SE (HR [95% CI]: 1.56 [1.12–2.18]). No significant differences in outcomes were observed between edoxaban and rivaroxaban, and MB risk did not differ significantly between edoxaban and any of the other DOACs. Conclusions Real-world DOAC use for stroke prevention in Spanish AF patients demonstrated a better safety outcome and lower all-cause mortality with similar effectiveness relative to VKA. Safety profiles and survival rates were similar across DOACs. Patients on edoxaban had a lower risk of IS/SE compared to apixaban or dabigatran, suggesting a favorable benefit-risk profile for stroke prevention in AF.