Thromboembolic events and major bleeding in frail patients with incident atrial fibrillation: a nationwide cohort study

Abstract Background Growing evidence suggests that frail patients presenting with atrial fibrillation (AF) are less likely to receive adequate oral anticoagulant therapy (OAC) despite high thromboembolic risk. There is a paucity of evidence investigating clinical outcomes in different antithrombotic strategies. Purpose To assess thromboembolic events, bleeding, and all-cause mortality according to OAC treatment regimen in a Danish nationwide cohort of frail patients with AF Method We included all patients with non-valvular AF between 2011 and 2018 who were aged ≥64 years and had a frailty risk score >5 according to the ICD-10 based Hospital Frailty Risk Score. Patients with an OAC indication other than atrial fibrillation were excluded. The cohort was stratified by treatment regimen: warfarin, NOACs standard dose, NOACs reduced dose, or no OAC, determined by treatment status within 60 days before and 30 days after AF diagnosis. Patients were followed from 30 days after AF diagnosis (index date) for the occurrence of thromboembolic events and major bleeding. Cumulative incidence functions were used to depict development of outcome risk over time using on the Aalen–Johansen estimator assuming death as competing risk. Results We identified 31,745 frail AF patients (mean age 80.7 years, 53.8% female); 16540 (52.1%) received no OAC, 2993 (9.4%) received warfarin, 6181 (19.5%) received standard dose NOACs, and 6031 (19.0%) revived reduced dose NOACs. Risk of developing the outcomes over time is depicted in Figure 1. At 1-year follow-up, the absolute risk of thromboembolic events was 5.0% for patients with no OAC, 4.2% for reduced dose NOACs, 4.1% for warfarin, and 3.4% for standard dose NOACs. Bleeding risk was 6.1% for warfarin, 5.4% for reduced dose NOACs, 5.2% for No OAC, and 5.1% for standard dose NOACs. Conclusions Most patients in this nationwide cohort of elderly frail AF patients received no OAC, which was associated with a high risk of thromboembolism. The associated risk of thromboembolism was lower in patients receiving other studied treatment modalities, which might suggest a benefit of OAC across different antithrombotic strategies in frail AF patients. However, differences in risk profile and patient specific factors are likely to influence our observations, and studies investigating the comparative effectiveness and safety of NOACs including dosage regimens in frail AF patients are warranted. Figure 1. Cumulative risk of events Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Bayer AG