Trends in Clinical Outcomes of Patients with Incident Atrial Fibrillation; Results from a Nationwide Registry

Background Atrial fibrillation (AF) is associated with the risk of stroke and death. Advancements in patient care, such as direct oral anticoagulant (DOAC) use, are expected to improve AF patients' outcomes. However, real-world data examining this expectation are sparse. Methods We performed a historical population-based study among patients of Israel's largest health-maintenance-organization among patients aged>21 years diagnosed with AF between 01/01/2010 and 01/01/2020. The study population was divided into early-era (2010-2014) and late-era (2015-2020). We compared the time-dependent 5-year risk of stroke, intracranial hemorrhage (ICH), gastrointestinal bleeding (GIB), or death. Results Of 98,241 patients (median-age:76, 51.3% women), 48,852 were in the early-era, and 49,389 were in the late-era. The late-era group had higher rates of OAC than the early-era group (51.3% vs. 33.5%, p<0.001). The predominant OACs were warfarin (28.4%) in the early-era and DOACs (45.1%) in the late-era. Five-year death rates were 17,226 (35.3%) and 14,702 (29.8%) in the early-era and late-era groups, respectively (p<0.001), and 5-year stroke rates were 1,997 (4.1%) and 1,474 (3.0%) in the early-era and late-era groups, respectively (p<0.001). In multivariate models, era-related death risk was mediated by between-group OAC changes (p-for-interaction<0.001). OAC was associated with lower death risk (aHR 0.93, 95%CI(0.89,0.96),p<0.001). The late-era group had a lower stroke risk (aHR 0.90 95%CI(0.82,0.99),p=0.037), which was associated with between-group OAC changes (p-for-interaction=0.002). OAC was associated with reduced stroke risk in the late-era only (aHR 0.87, 95%CI(0.78,0.97),p=0.012). The risk of ICH was similar across study groups (p=0.40). GIB risk was lower in the late-era (aHR 0.85 95%CI(0.78,0.93),p<0.001). OAC was associated with increased GIB risk in the early-era (aHR 1.32, 95%CI(1.21,1.43),p<0.001) but not in the late-era (aHR 1.06 95%CI(0.96,1.17),p=0.24). Conclusions Contemporary AF management is associated with lower stroke, death, and significant bleeding risks. The pendulum shift from warfarin to DOACs was associated with improved clinical benefits.Survival curves of the outcome