Factors affecting bleeding risk during anticoagulant therapy in patients with atrial fibrillation: observations from the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) study

Am Heart J. 2005 Apr;149(4):650-6. doi: 10.1016/j.ahj.2004.11.015.


Background: Stroke and systemic thromboembolism are serious problems for patients with atrial fibrillation (AF), but their incidence can be substantially reduced by appropriate anticoagulation. Bleeding is the major complication of anticoagulant treatment, and the relative risks for bleeding vs stroke must be considered when starting anticoagulation.

Methods: The AFFIRM trial included patients with AF and at least one risk factor for stroke, randomly assigning them to either a rate-control or rhythm-control strategy. All patients were initially treated with warfarin. The incidence of protocol-defined major and minor bleeding was documented during follow-up. Variables associated with bleeding were determined using a Cox proportional hazards model, using baseline and time-dependent covariates.

Results: The 4060 patients in the AFFIRM trial were followed for an average of 3.5 years. Major bleeding occurred in 260 patients, an annual incidence of approximately 2% per year, with no significant difference between the rate-control and rhythm-control groups. Increased age, heart failure, hepatic or renal disease, diabetes, first AF episode, warfarin use, and aspirin use were significantly associated with major bleeding. Minor bleeding was common in both treatment arms, with 738 patients reporting this problem in one or more visits.

Conclusions: Bleeding is a significant problem that complicates management of patients with AF. Risk factors for bleeding can be identified, and knowledge of these risk factors can be used to plan therapy.

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aged
  • Amiodarone / administration & dosage
  • Amiodarone / adverse effects
  • Amiodarone / therapeutic use
  • Anti-Arrhythmia Agents / administration & dosage
  • Anti-Arrhythmia Agents / adverse effects*
  • Anti-Arrhythmia Agents / therapeutic use
  • Anticoagulants / administration & dosage
  • Anticoagulants / adverse effects*
  • Anticoagulants / therapeutic use
  • Aspirin / administration & dosage
  • Aspirin / adverse effects
  • Aspirin / therapeutic use
  • Atrial Fibrillation / complications
  • Atrial Fibrillation / drug therapy*
  • Atrial Fibrillation / surgery
  • Atrial Fibrillation / therapy
  • Combined Modality Therapy
  • Drug Therapy, Combination
  • Female
  • Follow-Up Studies
  • Hemorrhage / chemically induced*
  • Hemorrhage / epidemiology
  • Humans
  • Incidence
  • Life Tables
  • Male
  • Middle Aged
  • Risk
  • Stroke / prevention & control
  • Thromboembolism / prevention & control
  • Warfarin / administration & dosage
  • Warfarin / adverse effects
  • Warfarin / therapeutic use


  • Anti-Arrhythmia Agents
  • Anticoagulants
  • Warfarin
  • Amiodarone
  • Aspirin