Context Warfarin has been shown to be highly efficacious for preventing thromboembolism
in atrial fibrillation in randomized trials, but its effectiveness and safety
in clinical practice is less clear.
Objective To evaluate the effect of warfarin on risk of thromboembolism, hemorrhage,
and death in atrial fibrillation within a usual care setting.
Design Cohort study assembled between July 1, 1996, and December 31, 1997,
and followed up through August 31, 1999.
Setting Large integrated health care system in Northern California.
Patients Of 13 559 adults with nonvalvular atrial fibrillation, 11 526
were studied, 43% of whom were women, mean age 71 years, with no known contraindications
to anticoagulation at baseline.
Main Outcomes Ischemic stroke, peripheral embolism, hemorrhage, and death according
to warfarin use and comorbidity status, as determined by automated databases,
review of medical records, and state mortality files.
Results Among 11 526 patients, 397 incident thromboembolic events (372
ischemic strokes, 25 peripheral embolism) occurred during 25 341 person-years
of follow-up, and warfarin therapy was associated with a 51% (95% confidence
interval [CI], 39%-60%) lower risk of thromboembolism compared with no warfarin
therapy (either no antithrombotic therapy or aspirin) after adjusting for
potential confounders and likelihood of receiving warfarin. Warfarin was effective
in reducing thromboembolic risk in the presence or absence of risk factors
for stroke. A nested case-control analysis estimated a 64% reduction in odds
of thromboembolism with warfarin compared with no antithrombotic therapy.
Warfarin was also associated with a reduced risk of all-cause mortality (adjusted
hazard ratio, 0.69; 95% CI, 0.61-0.77). Intracranial hemorrhage was uncommon,
but the rate was moderately higher among those taking vs those not taking
warfarin (0.46 vs 0.23 per 100 person-years, respectively; P = .003, adjusted hazard ratio, 1.97; 95% CI, 1.24-3.13). However,
warfarin therapy was not associated with an increased adjusted risk of nonintracranial
major hemorrhage. The effects of warfarin were similar when patients with
contraindications at baseline were analyzed separately or combined with those
without contraindications (total cohort of 13 559).
Conclusions Warfarin is very effective for preventing ischemic stroke in patients
with atrial fibrillation in clinical practice while the absolute increase
in the risk of intracranial hemorrhage is small. Results of randomized trials
of anticoagulation translate well into clinical care for patients with atrial