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(Stroke. 2009;40:1410.)
© 2009 American Heart Association, Inc.

Original Contributions

Effect of Age on Stroke Prevention Therapy in Patients With Atrial Fibrillation

The Atrial Fibrillation Investigators

Carl van Walraven, MD, MSc, FRCPC; Robert G. Hart, MD; Stuart Connolly, MD, FRCPC; Peter C. Austin, PhD; Jonathan Mant, MD, FFPH; F.D. Richard Hobbs, MD; Peter J. Koudstaal, MD, PhD; Palle Petersen, MD, DMSc, FCCP; Francisco Perez-Gomez, MD, FESC; J. Andre Knottnerus, MD, PhD; Beppie Boode, MD, PhD; Michael D. Ezekowitz, MD, PhD, FRCP, FACC Daniel E. Singer, MD

From the University of Ottawa and Ottawa Health Research Institute Canada (C.v.W.), Ottawa, Canada; the Institute for Clinical Evaluative Sciences (C.v.W., P.C.A.), Toronto, Canada; the University of Texas Health Science Center at San Antonio (R.G.H.), San Antonio, Texas; McMaster University (S.C.), Hamilton, Ontario, Canada; the Department of Public Health Sciences and Health Policy, Management and Evaluation (P.C.A.), University of Toronto, Toronto, Canada.; Primary Care Clinical Sciences (J.M., F.D.R.H.), University of Birmingham, Birmingham, UK; Erasmus Medical Center (P.J.K.), Rotterdam, The Netherlands; Copenhagen University Hospital (P.P.), Rigshospitalet, Denmark; Hospital Clinico San Carlos (F.P.-G.), Madrid, Spain; the University of Maastricht (J.A.K., B.B.), Maastricht, The Netherlands; Langenaur Institute for Medicine (M.D.E.), Wynnwood, Pa; and Harvard Medical School (D.E.S.), Boston, Mass.

Correspondence to Carl van Walraven, MD, MSc, FRCPC, Clinical Epidemiology Program, Ottawa Health Research Institute, ASB1-003, Ottawa Hospital, Civic Campus, 1053 Carling Avenue, Ottawa, Ontario, K1Y 4E9, Canada. E-mail carlv{at}ohri.ca

Background and Purpose— Stroke risk increases with age in patients who have nonvalvular atrial fibrillation. It is uncertain whether the efficacy of stroke prevention therapies in atrial fibrillation changes as patients age. The objective of this study was to determine the effect of age on the relative efficacy of oral anticoagulants (OAC) and antiplatelet (AP) therapy (including acetylsalicylic acid and triflusal) on ischemic stroke, serious bleeding, and vascular events in patients with atrial fibrillation.

Methods— This is an analysis of the Atrial Fibrillation Investigators database, which contains patient level-data from randomized trials of stroke prevention in atrial fibrillation. We used Cox regression models with age as a continuous variable that controlled for sex, year of randomization, and history of cerebrovascular disease, diabetes, hypertension, and congestive heart failure. Outcomes included ischemic stroke, serious bleeding (intracranial hemorrhage or systemic bleeding requiring hospitalization, transfusion, or surgery), and cardiovascular events (ischemic stroke, myocardial infarction, systemic embolism, or vascular death).

Results— The analysis included 8932 patients and 17 685 years of observation from 12 trials. Patient age increased risk of ischemic stroke (adjusted hazard ratio per decade increase 1.45; 95% CI, 1.26 to 1.66), serious bleeding (1.61; 1.47 to 1.77), and cardiovascular events (1.43; 1.33 to 1.53). Compared with placebo, OAC and AP significantly reduced the risk of ischemic stroke (OAC, 0.36; 0.29 to 0.45; AP, 0.81; 0.72 to 0.90) and cardiovascular outcomes (OAC, 0.59; 0.52 to 0.66; AP, 0.81; 0.75 to 0.88), whereas OAC increased risk of serious bleeding (1.56; 1.03 to 2.37). The relative benefit of OAC versus placebo or AP did not vary by patient age for any outcome. Compared with placebo, the relative benefit of AP for preventing ischemic stroke decreased significantly as patients aged (P=0.01).

Conclusions— As patients with atrial fibrillation age, the relative efficacy of AP to prevent ischemic stroke appears to decrease, whereas it does not change for OAC. Because stroke risk increases with age, the absolute benefit of OAC increases as patients get older.

Key Words: acute stroke • analysis • anticoagulation • antiplatelet drugs • aspirin • atrial fibrillation • biostatistics • cardiac emboli • cardiac embolism • cerebral infarct • clinical trials • database • epidemiology • outcomes • randomized controlled trials • warfarin