The net clinical benefit of warfarin anticoagulation in atrial fibrillation

Abstract

Background: Guidelines recommend warfarin use in patients with atrial fibrillation solely on the basis of risk for ischemic stroke without antithrombotic therapy. These guidelines rely on ischemic stroke rates observed in older trials and do not explicitly account for increased risk for hemorrhage.

Objective: To quantify the net clinical benefit of warfarin therapy in a cohort of patients with atrial fibrillation.

Design: Mixed retrospective and prospective cohort study of patients with atrial fibrillation between 1996 and 2003.

Setting: An integrated health care delivery system.

Patients: 13 559 adults with nonvalvular atrial fibrillation.

Measurements: Warfarin exposure, patient characteristics, CHADS(2) score (1 point for each of congestive heart failure, hypertension, age, and diabetes and 2 points for stroke), and outcome events were ascertained from health plan records and databases. Net clinical benefit was defined as the annual rate of ischemic strokes and systemic emboli prevented by warfarin minus intracranial hemorrhages attributable to warfarin, multiplied by an impact weight. The base-case impact weight was 1.5, reflecting the greater clinical impact of intracranial hemorrhage versus thromboembolism.

Results: Patients accumulated more than 66 000 person-years of follow-up. The adjusted net clinical benefit of warfarin for the cohort overall was 0.68% per year (95% CI, 0.34% to 0.87%). Adjusted net clinical benefit was greatest for patients with a history of ischemic stroke (2.48% per year [CI, 0.75% to 4.22%]) and for those 85 years or older (2.34% per year [CI, 1.29% to 3.30%]). The net clinical benefit of warfarin increased from essentially zero in CHADS(2) stroke risk categories 0 and 1 to 2.22% per year (CI, 0.58% to 3.75%) in CHADS(2) categories 4 to 6. The patterns of results were preserved when weighting factors for intracranial hemorrhage of 1.0 and 2.0 were used.

Limitations: Residual confounding is a possibility. Some outcome events were probably missed by the screening algorithm or when medical records were unavailable.

Conclusion: Expected net clinical benefit of warfarin therapy is highest among patients with the highest untreated risk for stroke, which includes the oldest age category. Risk assessment that incorporates both risk for thromboembolism and risk for intracranial hemorrhage provides a more quantitatively informed basis for the decision on antithrombotic therapy in patients with atrial fibrillation.

Primary funding source: National Institute on Aging; National Heart, Lung, and Blood Institute; and Massachusetts General Hospital.

Figure

The net clinical benefit of warfarin by age group (top) and CHADS₂ score (bottom). Net clinical benefit is plotted as the adjusted, weighted adverse events prevented per 100 person-years by warfarin treatment, according to age group and CHADS₂ score, respectively. Intracranial hemorrhage is weighted as 1.5 times the value of thromboembolism (see Methods section). Stratified rates for CHADS₂ score are not further adjusted. CHADS₂ = Congestive Heart Failure/Hypertension/Age/Diabetes/Prior Stroke₂.

Figure

The net clinical benefit of warfarin by age group (top) and CHADS₂ score (bottom). Net clinical benefit is plotted as the adjusted, weighted adverse events prevented per 100 person-years by warfarin treatment, according to age group and CHADS₂ score, respectively. Intracranial hemorrhage is weighted as 1.5 times the value of thromboembolism (see Methods section). Stratified rates for CHADS₂ score are not further adjusted. CHADS₂ = Congestive Heart Failure/Hypertension/Age/Diabetes/Prior Stroke₂.