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Original Articles

Anticoagulation Control and Prediction of Adverse Events in Patients With Atrial Fibrillation

A Systematic Review

Yi Wan, MSc; Carl Heneghan, MA, MRCGP; Rafael Perera, DPhil; Nia Roberts, MSc; Jennifer Hollowell, PhD; Paul Glasziou, PhD, FRACGP; Clare Bankhead, DPhil and Yongyong Xu, PhD

From the Department of Health Statistics (Y.W., Y.X.), Fourth Military Medical University, Xi’an, China; Department of Primary Health Care (Y.W., C.H., R.P., N.R., P.G., C.B.) and National Perinatal Epidemiology Unit (J.H.), Department of Public Health, University of Oxford, Oxford, United Kingdom; and Health Care Evaluation Group (J.H.), Department of Epidemiology and Public Health, University College London, London, United Kingdom.

Correspondence to Yi Wan, Department of Primary Health Care, University of Oxford, Rosemary Rue Building, Old Road Campus, Headington, Oxford OX3 7LF, United Kingdom. E-mail mailwy{at}hotmail.com

Received June 2, 2008; accepted September 9, 2008.

Background— To date, there has been no systematic examination of the relationship between international normalized ratio (INR) control measurements and the prediction of adverse events in patients with atrial fibrillation on oral anticoagulation.

Methods and Results— We searched MEDLINE, EMBASE, and Cochrane through January 2008 for studies of atrial fibrillation patients receiving vitamin-K antagonists that reported INR control measures (percentage of time in therapeutic range [TTR] and percentage of INRs in range) and major hemorrhage and thromboembolic events. In total, 47 studies were included from 38 published articles. TTR ranged from 29% to 75%; percentage of INRs ranged from 34% to 84%. From studies reporting both measures, TTR significantly correlated with percentage of INRs in range (P<0.001). Randomized controlled trials had better INR control than retrospective studies (64.9% versus 56.4%; P=0.01). TTR negatively correlated with major hemorrhage (r=–0.59; P=0.002) and thromboembolic rates (r=–0.59; P=0.01). This effect was significant in retrospective studies (major hemorrhage, r=–0.78; P=0.006 and thromboembolic rate, r=–0.88; P=0.03) but not in randomized controlled trials (major hemorrhage, r=0.18; P=0.33 and thromboembolic rate, r=–0.61; P=0.07). For retrospective studies, a 6.9% improvement in the TTR significantly reduced major hemorrhage by 1 event per 100 patient-years of treatment (95% CI, 0.29 to 1.71 events).

Conclusions— In atrial fibrillation patients receiving orally administered anticoagulation treatment, TTR and percentage of INRs in range effectively predict INR control. Data from retrospective studies support the use of TTR to accurately predict reductions in adverse events.

Key Words: anticoagulants • atrial fibrillation • hemorrhage • thrombosis • international normalized ratio

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CLINICAL PERSPECTIVE

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