Meta-analysis: Antithrombotic Therapy to Prevent Stroke in Patients Who Have Nonvalvular Atrial Fibrillation

19 June 2007 | Volume 146 Issue 12 | Pages 857-867

Background: Atrial fibrillation is a strong independent risk factor for stroke.

Purpose: To characterize the efficacy and safety of antithrombotic agents for stroke prevention in patients who have atrial fibrillation, adding 13 recent randomized trials to a previous meta-analysis.

Data Sources: Randomized trials identified by using the Cochrane Stroke Group search strategy, 1966 to March 2007, unrestricted by language.

Study Selection: All published randomized trials with a mean follow-up of 3 months or longer that tested antithrombotic agents in patients who have nonvalvular atrial fibrillation.

Data Extraction: Two coauthors independently extracted information regarding interventions; participants; and occurrences of ischemic and hemorrhagic stroke, major extracranial bleeding, and death.

Data Synthesis: Twenty-nine trials included 28 044 participants (mean age, 71 years; mean follow-up, 1.5 years). Compared with the control, adjusted-dose warfarin (6 trials, 2900 participants) and antiplatelet agents (8 trials, 4876 participants) reduced stroke by 64% (95% CI, 49% to 74%) and 22% (CI, 6% to 35%), respectively. Adjusted-dose warfarin was substantially more efficacious than antiplatelet therapy (relative risk reduction, 39% [CI, 22% to 52%]) (12 trials, 12 963 participants). Other randomized comparisons were inconclusive. Absolute increases in major extracranial hemorrhage were small (0.3% per year) on the basis of meta-analysis.

Limitation: Methodological features and quality varied substantially and often were incompletely reported.

Conclusions: Adjusted-dose warfarin and antiplatelet agents reduce stroke by approximately 60% and by approximately 20%, respectively, in patients who have atrial fibrillation. Warfarin is substantially more efficacious (by approximately 40%) than antiplatelet therapy. Absolute increases in major extracranial hemorrhage associated with antithrombotic therapy in participants from the trials included in this meta-analysis were less than the absolute reductions in stroke. Judicious use of antithrombotic therapy importantly reduces stroke for most patients who have atrial fibrillation.

Editors' Notes Context Thirteen new randomized, controlled trials are available since a 1999 meta-analysis of antithrombotic agents for stroke prevention in patients with atrial fibrillation. Contribution This updated meta-analysis shows that, compared with placebo, adjusted-dose warfarin reduces stroke risk by 64% (6 trials) and antiplatelet agents reduce stroke risk by 22% (8 trials). Meta-analysis of 12 trials shows that adjusted-dose warfarin is more effective than antiplatelet therapy, but it doubles the risk for major extracranial and intracranial hemorrhage. However, absolute rates of these adverse events were only 0.2% per year. Implication Additional trials are unlikely to substantially change current estimates of the effectiveness of vitamin K antagonists and antiplatelet agents in stroke prevention in patients with atrial fibrillation. —The Editors

 

Author and Article Information

From the University of Texas Health Science Center, San Antonio, Texas, and Mayo Clinic Scottsdale, Scottsdale, Arizona.

Note: Dr. Hart and Ms. Pearce were leaders of the SPAF trials (1987 to 1999), which were funded by the National Institute of Neurologic Disorders and Stroke. Dr. Hart also served on the data and safety monitoring boards of the SPORTIF III and V trials, which were sponsored by AstraZeneca Pharmaceuticals (Wilmington, Delaware), and on the stroke advisory committee of the ACTIVE-W trial. Drs. Hart and Aguilar and Ms. Pearce are coauthors on the Cochrane Stroke Group modules on this topic.

Potential Financial Conflicts of Interest: None disclosed.

Requests for Single Reprints: Robert G. Hart, MD, Department of Medicine (Neurology), University of Texas Health Science Center, 7703 Floyd Curl Drive, MC# 7883, San Antonio, TX 78229-3900; e-mail, hartr{at}uthscsa.edu.

Current Author Addresses: Dr. Hart: Department of Medicine (Neurology), University of Texas Health Science Center, 7703 Floyd Curl Drive, MC# 7883, San Antonio, TX 78229-3900.

Ms. Pearce: 2509 Bel Air Court, Minot, ND 58703.

Dr. Aguilar: Department of Neurology, Division of Cerebrovascular Disease, Mayo Clinic, 5777 East Mayo Boulevard, Phoenix, AZ 85054.

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