Frailty phenotype as a predictor of bleeding and mortality in ambulatory patients receiving direct oral anticoagulants

Abstract Background Limited prospective data exist about the clinical relevance of frailty in patients with atrial fibrillation (AF) or venous thromboembolism (VTE) receiving direct oral anticoagulants (DOACs). The aim of this study was to evaluate whether frailty phenotype identifies DOAC‐treated patients at higher risk of adverse clinical outcomes. Methods Consecutive, adult outpatients treated with DOACs for AF or VTE were prospectively enrolled. Patients were classified as frail, pre‐frail, or non‐frail according to frailty phenotype. Study outcomes were clinically relevant bleeding, including major and clinically relevant non‐major bleeding, arterial and venous thromboembolism, and all‐cause mortality. Results 236 patients (median age 78 years, 44% females) were included, of whom 156 (66%) had AF and 80 (34%) VTE. Ninety‐eight (41%) patients were frail, 115 (49%) pre‐frail, and 23 (10%) non‐frail. Inappropriately high or low dose DOAC was used in 33% of frail and in 20% of non‐frail or pre‐frail patients. Over a median follow‐up of 304 days, the incidence of clinically relevant bleeding, thromboembolism, and mortality were 20%, 4%, 9% in frail, and 10%, 3%, and 2% in pre‐frail, respectively, while no study outcome occurred among non‐frail patients. Risk ratios (95% confidence intervals) for these outcomes in frail versus pre‐frail and non‐frail patients were respectively 2.5 (1.8, 3.7), 1.9 (0.9, 4.0), and 6.3 (2.9, 13.6). Conclusion In a prospective cohort of ambulatory patients receiving DOAC treatment for AF or VTE, frailty phenotype identified patients at higher risk of bleeding and all‐cause mortality. Frailty assessment could be valuable to guide targeted interventions potentially improving patient prognosis.