Impact of Modifiable Bleeding Risk Factors on Major Bleeding in Patients With Atrial Fibrillation Anticoagulated With Rivaroxaban

J Am Heart Assoc. 2020 Mar 3;9(5):e009530. doi: 10.1161/JAHA.118.009530. Epub 2020 Feb 21.


Background Reducing major bleeding events is a challenge when managing anticoagulation in patients with atrial fibrillation. This study evaluated the impact of modifiable and nonmodifiable bleeding risk factors in patients with atrial fibrillation receiving rivaroxaban and estimated the impact of risk factor modification on major bleeding events. Methods and Results Modifiable and nonmodifiable risk factors associated with major bleeding events were identified from the XANTUS (Xarelto for Prevention of Stroke in Patients With Atrial Fibrillation) prospective registry data set (6784 rivaroxaban-treated patients). Parameters showing univariate association with bleeding were used to construct a multivariable model identifying independent risk factors. Modeling was used to estimate attributed weights to risk factors. Heavy alcohol use (hazard ratio [HR]=2.37; 95% CI 1.24-4.53); uncontrolled hypertension (HR after parameter-wise shrinkage=1.79; 95% CI 1.05-3.05); and concomitant treatment with antiplatelets, nonsteroidal anti-inflammatory drugs, or paracetamol (HR=1.80; 95% CI 1.24-2.61) were identified as modifiable, independent bleeding risk factors. Increasing age (HR=1.25 [per 5-year increment]; 95% CI 1.12-1.38); heart failure (HR=1.97; 95% CI 1.36-2.86); and vascular disease (HR=1.91; 95% CI 1.32-2.77) were identified as nonmodifiable bleeding risk factors. Overall, 128 (1.9%) patients experienced major bleeding events; of these, 11% had no identified bleeding risk factors, 50% had nonmodifiable bleeding risk factors only, and 39% had modifiable bleeding risk factors (with or without nonmodifiable risk factors). The presence of 1 modifiable bleeding risk factor doubled the risk of major bleeding. Conclusions Elimination of modifiable bleeding risk factors is a potentially effective strategy to reduce bleeding risk in atrial fibrillation patients receiving rivaroxaban. Clinical Trial Registration URL: Unique identifier: NCT01606995.

Keywords: anticoagulation; independent predictor; major bleeding; modeling study; modifiable risk factor.

Publication types

  • Multicenter Study
  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alcohol Drinking / adverse effects
  • Anti-Inflammatory Agents, Non-Steroidal / adverse effects
  • Atrial Fibrillation / complications
  • Atrial Fibrillation / diagnosis
  • Atrial Fibrillation / drug therapy*
  • Europe
  • Factor Xa Inhibitors / adverse effects*
  • Female
  • Hemorrhage / chemically induced
  • Hemorrhage / prevention & control*
  • Humans
  • Hypertension / complications
  • Male
  • Middle Aged
  • Platelet Aggregation Inhibitors / adverse effects
  • Prospective Studies
  • Registries
  • Risk Assessment
  • Risk Factors
  • Rivaroxaban / adverse effects*
  • Stroke / diagnosis
  • Stroke / etiology
  • Stroke / prevention & control*
  • Treatment Outcome


  • Anti-Inflammatory Agents, Non-Steroidal
  • Factor Xa Inhibitors
  • Platelet Aggregation Inhibitors
  • Rivaroxaban

Associated data