Oral anticoagulants for preventing stroke in patients with non-valvular atrial fibrillation and no previous history of stroke or transient ischemic attacks.
BACKGROUND
Non-valvular atrial fibrillation (AF) is associated with an increased risk of stroke.


OBJECTIVE
The objective of this review was to characterize the efficacy and safety of oral anticoagulation (OAC) with vitamin K antagonists for the primary prevention of stroke in patients with chronic AF.


METHODS
We searched the Cochrane Stroke Group Specialised Register of Trials (June 1999), MEDLINE database, and the database of the Antithrombotic Trialists Collaboration, as well as reference lists of relevant articles.


METHODS
All randomized controlled trials comparing the value of OAC versus control in patients with non-valvular chronic atrial fibrillation and no history of transient ischemic attack (TIA) or stroke.


METHODS
Trials for inclusion were independently selected by two reviewers who also extracted each outcome and double-checked the data. The Peto method was used for combining odds ratios. All analysis were, as far as possible, "intention-to-treat". Since the published results of four trials included 3-8% of participants with prior stroke or TIA, unpublished results excluding these participants were obtained from the Atrial Fibrillation Investigators.


RESULTS
Of 2313 participants without prior cerebral ischemia from five trials, about half (n = 1154) were randomized to adjusted-dose OAC with an estimated mean INRs ranging between 2.0-2.6 during 1.5 years/participant average follow-up. Participant features and study quality were similar between trials. OAC was associated with large, highly statistically significant reductions in ischemic stroke (OR = 0.34, 95% CI 0.23 - 0.52), all stroke (OR = 0.39, 95% CI 0.26 - 0. 59), all disabling or fatal stroke (OR = 0.47, 95% CI 0.28 - 0.80), and the combined endpoint of all stroke, MI or vascular death (OR = 0.56, 95% CI 0.42 - 0.76). The observed rates of intracranial and extracranial hemorrhage not significantly increased by OAC therapy, but confidence intervals were wide.


CONCLUSIONS
Adjusted-dose OAC (achieved INRs between 2-3) reduces stroke as well as disabling/fatal stroke for patients with nonvalvular AF, and these benefits were not substantially offset by increased bleeding among participants in randomized clinical trials. Limitations include relatively short follow-up and imprecise estimates of bleeding risks from these selected participants. For primary prevention in AF patients who have an average stroke rate of 4%/year, about 25 strokes and about 12 disabling fatal strokes would be prevented yearly for every 1000 given OAC.
Benavente
O
O
Division of Neurology, Department of Medicine, University of Texas. Health Sciences Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, Texas 78284-7883, USA. benavente@uthscsa.edu .
Hart
R
R
Koudstaal
P
P
Laupacis
A
A
McBride
R
R
D000925:Anticoagulants / Q000627:therapeutic use*; D001281:Atrial Fibrillation / Q000150:complications*; D006801:Humans; D020521:Stroke / Q000209:etiology* / Q000517:prevention & control*
D000925:Anticoagulants