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van Walraven C, Hart RG, Singer DE, et al. Oral Anticoagulants vs Aspirin in Nonvalvular Atrial Fibrillation: An Individual Patient Meta-analysis. JAMA. 2002;288(19):2441–2448. doi:10.1001/jama.288.19.2441
Author Affiliations: Clinical Epidemiology Unit, Ottawa Health Research Institute (Dr van Walraven); Institute for Clinical Evaluative Sciences (Drs van Walraven and Laupacis); Canadian Institutes for Health Research (Dr Laupacis), Ottawa, Ontario; Department of Medicine, University of Texas, San Antonio (Dr Hart); Clinical Epidemiology Unit, General Medicine Division, Massachusetts General Hospital, Boston (Drs Singer and Chang); McMaster University, Hamilton, Ontario (Dr Connolly); Hvidovre University Hospital, Copenhagen, Denmark (Dr Petersen); Department of Neurology, Erasmus MC, Rotterdam (Dr Koudstaal) and University of Maastricht, Maastricht (Dr Hellemons), the Netherlands. Dr van Walraven is an Ontario Ministry of Health Career Scientist.
Clinical Cardiology Section Editor: Michael S. Lauer, MD,
Context Patients with nonvalvular atrial fibrillation (AF) have an increased
risk of stroke and other vascular events.
Objective To compare the risk of vascular and bleeding events in patients with
nonvalvular AF treated with vitamin K –inhibiting oral anticoagulants
or acetylsalicylic acid (aspirin).
Design Pooled analysis of patient-level data from 6 published, randomized clinical
Patients A total of 4052 patients with AF randomly assigned to receive therapeutic
doses of oral anticoagulant or aspirin with or without low-dose oral anticoagulants.
Main Outcome Measures Ischemic and hemorrhagic stroke, other cardiovascular events, all-cause
death, and major bleeding events. Person-year incidence rates were calculated
to provide crude comparisons. Relative efficacy was assessed using proportional
hazards modeling stratified by study. The variation of the oral anticoagulant's
relative effect by pertinent patient factors was explored with interaction
terms. All analyses were conducted using the intention-to-treat principle.
Results Patients receiving oral anticoagulant and aspirin were balanced for
important prognostic factors. There was no significant heterogeneity between
trials in the relative efficacy of oral anticoagulant vs aspirin for any outcome.
Patients receiving oral anticoagulant were significantly less likely to experience
any stroke (2.4 vs 4.5 events per 100 patient-years; hazard ratio [HR], 0.55;
95% confidence interval [CI], 0.43-0.71), ischemic stroke (HR, 0.48; 95% CI,
0.37-0.63), or cardiovascular events (HR, 0.71; 95% CI, 0.59-0.85) but were
more likely to experience major bleeding (2.2 vs 1.3 events per 100 patient-years;
HR, 1.71; 95% CI, 1.21-2.41). The reduction in ischemic stroke risk was similar
in patients with paroxysmal AF (1.5 vs 4.7 events per 100 patient-years; HR,
0.32; 95% CI, 0.16-0.61; P<.001). Treating 1000
patients with AF for 1 year with oral anticoagulant rather than aspirin would
prevent 23 ischemic strokes while causing 9 additional major bleeds. Overall
all-cause survival did not differ but appeared to improve for oral anticoagulant
patients 3 years after therapy was started.
Conclusions Compared with aspirin, oral anticoagulant significantly decreases the
risk of all strokes, ischemic strokes, and cardiovascular events for patients
with nonvalvular chronic or paroxysmal AF but modestly increases the absolute
risk of major bleeding. The balance of benefits and risks varies by patient
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