Primary stroke prevention in nonvalvular atrial fibrillation: implementing the clinical trial findings.
OBJECTIVE
To review the clinical trials evaluating warfarin for primary stroke prophylaxis in nonvalvular atrial fibrillation (NVAF), to discuss the relative benefits and risks of warfarin versus aspirin therapy, and to review the clinical practice guidelines and identify potential barriers to their implementation in clinical practice.


METHODS
A MEDLINE literature search was performed to identify clinical trials of antithrombotic therapy for NVAF, clinical practice guidelines, studies evaluating physician practices and attitudes, cost-effectiveness studies, and pertinent review articles. Key search terms included atrial fibrillation, stroke, antithrombotic, warfarin, aspirin, and cost-effectiveness.


METHODS
Prospective, randomized clinical trials were selected for analysis. Clinical practice guidelines from recognized panels of experts were reviewed. Comprehensive review articles were selected.


RESULTS
NVAF is a common arrhythmia that is associated with a substantial risk for stroke. Seven prospective, randomized, clinical trials have conclusively demonstrated the efficacy of warfarin for stroke prevention. The greatest benefits are achieved in older patients and those with comorbidities that increase their risk for stroke. The potential benefits of preventing a devastating stroke, however, must be weighed against the potential for bleeding complications. Warfarin has been shown to be cost-effective in high-risk patients, provided the rate of complications is minimized. Nonetheless, many physicians remain hesitant to implement warfarin therapy in older, high-risk patients. The clinical data on aspirin are less consistent than those observed with warfarin. Aspirin appears to be most effective in younger individuals or those considered to be at low risk for stroke.


CONCLUSIONS
In patients with NVAF, the personal, social, and economic consequences of stroke are often devastating. Clinical trials have provided definitive proof that the risks of stroke can be significantly reduced through the use of appropriate antithrombotic therapy. Despite this evidence and the recommendations of a number of clinical practice guidelines, variations in care exist that continue to place patients at risk. Additional outcomes research is needed to evaluate the impact of the clinical trial findings and practice guidelines on clinical practice and to develop methods for overcoming barriers to implementation.
Howard
P A
PA
Department of Pharmacy Practice, School of Pharmacy, University of Kansas Medical Center, Kansas City 66160, USA.
Duncan
P W
PW
D000368:Aged; D000925:Anticoagulants / Q000009:adverse effects / Q000627:therapeutic use*; D001281:Atrial Fibrillation / Q000150:complications*; D002561:Cerebrovascular Disorders / Q000150:complications / Q000517:prevention & control*; D003362:Cost-Benefit Analysis; D016527:Drug Costs; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D008297:Male; D017410:Practice Guidelines as Topic; D014859:Warfarin / Q000009:adverse effects / Q000191:economics / Q000627:therapeutic use*
D000925:Anticoagulants; D014859:Warfarin