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Original Articles

Should Patient Characteristics Influence Target Anticoagulation Intensity for Stroke Prevention in Nonvalvular Atrial Fibrillation?

The ATRIA Study

Daniel E. Singer, MD; Yuchiao Chang, PhD; Margaret C. Fang, MD, MPH; Leila H. Borowsky, MPH; Niela K. Pomernacki, RD; Natalia Udaltsova, PhD and Alan S. Go, MD

From the Clinical Epidemiology Unit, General Medicine Division (D.E.S., Y.C., L.H.B.), Massachusetts General Hospital, Boston, Mass; the Department of Medicine (M.C.F., A.S.G.), University of California, San Francisco, Calif; the Division of Research (A.S.G., N.K.P., N.U.), Kaiser Permanente of Northern California, Oakland, Calif; and the Departments of Epidemiology and Biostatistics (A.S.G.), University of California, San Francisco, Calif.

Correspondence to Daniel E. Singer, MD, Clinical Epidemiology Unit, Massachusetts General Hospital, 50 Staniford St, 9th Floor, Boston, MA 02114. E-mail dsinger{at}partners.org

Received October 24, 2008; accepted March 9, 2009.

Background— Randomized trials and observational studies support using an international normalized ratio (INR) target of 2.0 to 3.0 for preventing ischemic stroke in atrial fibrillation. We assessed whether the INR target should be adjusted based on selected patient characteristics.

Methods and Results— We conducted a case–control study nested within the ATRIA cohort’s 9217 atrial fibrillation patients taking warfarin to define the relationship between INR level and the odds of thromboembolism (TE; mainly stroke) and of intracranial hemorrhage (ICH) relative to INR 2.0 to 2.5. We identified 396 TE cases and 164 ICH cases during follow-up. Each case was compared with 4 randomly selected controls matched on calendar date and stroke risk factors using matched univariable analyses and conditional logistic regression. We explored modification of the INR–outcome relationships by the following stroke risk factors: prior stroke, age, and CHADS₂ risk score. Overall, the odds of TE were low and stable above INR 1.8. Compared with INR 2.0 to 2.5, the relative odds of TE increased strikingly at INR <1.8 (eg, odds ratio, 3.72; 95% CI, 2.67 to 5.19, at INR 1.4 to 1.7). The odds of ICH increased markedly at INR values >3.5 (eg, odds ratio, 3.56; 95% CI: 1.70 to 7.46, at INR 3.6 to 4.5). The relative odds of ICH were consistently low at INR <3.6. There was no evidence of lower ICH risk at INR levels <2.0. These patterns of risk did not differ substantially by history of stroke, age, or CHADS₂ risk score.

Conclusions— Our results confirm that the current standard of INR 2.0 to 3.0 for atrial fibrillation falls in the optimal INR range. Our findings do not support adjustment of INR targets according to previously defined stroke risk factors.

Key Words: atrial fibrillation • anticoagulation • prevention and control • stroke

The online-only Data Supplement is available at http://circoutcomes.ahajournals.org/cgi/content/full/10.1161/CIRCOUTCOMES.108.830232/DC1.