Clinical Investigations
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

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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.

Section snippets

Methods

Four thousand sixty patients were randomized in the AFFIRM trial and their clinical characteristics have been previously reported.15., 16. The average length of follow-up was 3.5 years (range 0 to 5.9 years). The primary end point was total mortality, analyzed by intention-to-treat. Secondary end points included composites of total mortality, disabling intracranial bleeding (subdural and/or subarachnoid hemorrhage, intraparenchymal hemorrhage), stroke (embolus, thrombosis, hemorrhage),

Results

Baseline characteristics for patients with and those without major bleeding events are summarized in Table I. Patients with major bleeding events were older and more likely to have a history of congestive heart failure, diabetes, or hepatic or renal disease.

Numbers and actuarial rates of major bleeding events are shown in Table II. Two hundred sixty patients (9.2%) had at least one major bleeding event. Of these, 136 had been randomized to the rate-control group and 124 to the rhythm-control

Discussion

Randomized clinical trials have shown that anticoagulation with warfarin results in a 60% to 70% reduction in the risk of stroke and systemic thromboembolism during AF.4., 5., 6., 7., 8., 9., 10. The efficacy of warfarin is even higher if an on-therapy, rather than an intention-to-treat analysis, is used.16 Because chronic anticoagulation also raises the risk of bleeding complications, current guidelines recommend warfarin only for those patients with AF in whom the risk for thromboembolic

References (32)

  • P. Petersen et al.

    Placebo-controlled randomised trial of warfarin and aspirin for prevention of thromboembolic complications in chronic atrial fibrillation: the Copenhagen AFASAK study

    Lancet

    (1989)
  • Secondary prevention in non-rheumatic atrial fibrillation after transient ischaemic attack or minor stroke: EAFT (European Atrial Fibrillation Trial) Study Group

    Lancet

    (1993)
  • The effect of low-dose warfarin on the risk of stroke in patients with nonrheumatic atrial fibrillation

    N Engl J Med

    (1990)
  • Bleeding during antithrombotic therapy in patients with atrial fibrillation

    Arch Intern Med

    (1996)
  • Stroke prevention with the oral direct thrombin inhibitor ximelagatran compared with warfarin in patients with non-valvular atrial fibrillation (SPORTIF III): randomised controlled trial

    Lancet

    (2003)
  • A comparison of rate control and rhythm control in patients with atrial fibrillation

    N Engl J Med

    (2002)
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    The AFFIRM investigators and their affiliations are listed in Ref. [13].

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