Clinical phenotype of anticoagulant discontinuation and the long-term prognosis in atrial fibrillation patients with high bleeding risk: A report from the GLORIA-AF registry

Background Discontinuation of oral anticoagulants (OACs) in patients with atrial fibrillation (AF) at high risk of bleeding is commonly seen. Objective This study aimed to explore risk factors leading to OAC discontinuation and the impact on clinical events in patients with AF at high bleeding risk. Methods From the prospective, multicenter Global Registry on Long-Term Antithrombotic Treatment in Patients With Atrial Fibrillation study, we analyzed, by OAC discontinuation, all-cause death, cardiovascular (CV) death, major adverse CV events (MACEs), thromboembolism (TE), major bleeding, stroke, and myocardial infarction during follow-up. The hazard ratio (HR) and confidence interval (CI) were determined using Cox regression. Results Of 3131 patients (age 74.9 ± 7.3 years, 39.5% male) with a HAS-BLED score of ≥3, 633 (20.2%) stopped OAC during follow-up. After multivariate adjustment, age of ≥80 years (HR 1.26, 95% CI 1.05-1.50), older with frailty (HR 1.33, 95% CI 1.12-1.94), chronic kidney disease (HR 1.36, 95% CI 1.14-1.63), chronic obstructive pulmonary disease (HR 1.56, 95% CI 1.20-2.03), peripheral arterial disease (HR 1.38, 95% CI 1.03-1.87), multimorbidity (HR 1.68, 95% CI 1.20-2.36), and polypharmacy (HR 1.59, 95% CI 1.24-2.05) were associated with OAC discontinuation. The patients who stopped OACs during follow-up had a higher risk of all-cause death (HR 1.74, 95% CI 1.35-2.25), CV death (HR 2.01, 95% CI 1.34-3.03), MACE (HR 2.37, 95% CI 1.79-3.14), TE (HR 1.96, 95% CI 1.28-2.99), major bleeding (HR 4.35, 95% CI 2.79-6.78), stroke (HR 2.42, 95% CI 1.57-3.73), and myocardial infarction (HR 2.02, 95% CI 1.12-3.66) after OAC discontinuation. The incidence of OAC discontinuation was higher in the patients with vitamin K antagonist than non-vitamin K oral anticoagulants (23.1% vs 19.3, P =.026). OAC discontinuation rate was consistent across regions, and the risk of clinical events was similar in the vitamin K antagonist and non-vitamin K oral anticoagulant groups. Conclusion Being an older patient with frailty and having chronic kidney disease, chronic obstructive pulmonary disease, peripheral arterial disease, multimorbidity, and polypharmacy were risk factors for OAC discontinuation. OAC discontinuation was independently associated with a higher risk of mortality, major bleeding, TE, and MACE in patients with AF at high risk of bleeding.