Risk of major bleeding in elderly patients with atrial fibrillation on direct oral anticoagulants: real world experience

Int J Clin Pharm. 2020 Apr;42(2):445-452. doi: 10.1007/s11096-020-01008-1. Epub 2020 Mar 13.


Background The efficacy and safety of direct oral anticoagulants is well established in patients with atrial fibrillation. However, data on their use in the oldest old patients (≥ 85 years), who have the highest risk of bleeding, is scarce. Objective The aim of this study was to evaluate the safety of direct oral anticoagulants in the oldest old patients with atrial fibrillation and assess the impact of age on major bleeding events. Setting Anticoagulation Clinic of the Department of Vascular Diseases, University Medical Centre Ljubljana, Slovenia. Methods From our single-centre prospective registry we enrolled 2260 consecutive atrial fibrillation patients aged ≥ 65 years that were started on dabigatran, rivaroxaban or apixaban. The mean duration of treatment exposure was 735 days. The primary outcome was the incidence of major bleeding. The incidence of thromboembolic events and death were also assessed. Potential risk factors for major bleeding were evaluated using Cox regression analysis. Main outcome measure Rate of major bleeding. Results During the follow-up 106 patients experienced major bleeding (2.3%/year). The oldest old patients (≥ 85 years) had the highest risk of any major bleeding (HR 2.50, 95% CI 1.44-4.32, p = 0.001), intracranial bleeding (HR 4.74, 95% CI 1.48-15.14, p < 0.01) and major gastrointestinal bleeding (HR 2.32, 95% CI 1.10-4.89, p < 0.03) compared to the group of patients aged 65-74 years, even though the majority of them were treated with reduced doses of direct oral anticoagulants. Significant predictors for major bleeding were age group ≥ 85 years (HR 2.52, 95% CI 1.43-4.47, p = 0.001) and history of bleeding (HR 3.32, 95% CI 1.87-5.90, p < 0.001). The incidence of a composite of stroke, transient ischemic attack and systemic embolism was 1.3%/year. Conclusion In this prospective real-world clinical study we have shown that the oldest old patients have the highest risk of major bleeding, which is further increased with a patient's history of bleeding.

Keywords: Atrial fibrillation; Direct oral anticoagulants; Elderly; Major bleeding; Oldest old.

Publication types

  • Observational Study

MeSH terms

  • Age Factors
  • Aged
  • Aged, 80 and over
  • Anticoagulants / adverse effects*
  • Anticoagulants / therapeutic use
  • Atrial Fibrillation / drug therapy
  • Comorbidity
  • Dose-Response Relationship, Drug
  • Embolism / epidemiology
  • Embolism / prevention & control
  • Factor Xa Inhibitors / adverse effects*
  • Female
  • Health Status
  • Hemorrhage / chemically induced*
  • Humans
  • Ischemic Attack, Transient / epidemiology
  • Ischemic Attack, Transient / prevention & control
  • Male
  • Memory, Episodic
  • Slovenia / epidemiology
  • Socioeconomic Factors
  • Stroke / epidemiology
  • Stroke / prevention & control


  • Anticoagulants
  • Factor Xa Inhibitors