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Aging and the Anticoagulant Response to Warfarin Therapy

Jerry H. Gurwitz, MD; Jerry Avorn, MD; Dennis Ross-Degnan, ScD; Igor Choodnovskiy, BS; and Jack Ansell, MD
[+] Article, Author, and Disclosure Information

Grant Support: By a grant from the Medications and Aging Program of the John A. Hartford Foundation. Dr. Gurwitz is the recipient of a clinical investigator award (K08 AG00510-01) from the National Institute on Aging.

Request for Reprints: Jerry H. Gurwitz, MD, Program for the Analysis of Clinical Strategies, 333 Longwood Avenue, Boston, MA 02115

Current Author Addresses: Drs. Gurwitz, Avorn, and Ross-Degnan and Mr. Choodnovskiy: Program for the Analysis of Clinical Strategies, 333 Longwood Avenue, Boston, MA 02115.

Dr. Ansell: Department of Medicine, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655.

© 1992 American College of PhysiciansAmerican College of Physicians

Ann Intern Med. 1992;116(11):901-904. doi:10.7326/0003-4819-116-11-901
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Objective: To assess the effect of aging on the anticoagulant response to warfarin.

Design: Retrospective cohort study.

Setting: A university hospital outpatient anticoagulation clinic.

Patients: All patients (n = 530) monitored in the anticoagulation clinic over a 10-year period (1980 to 1990). The 530 study patients had a mean age of 61.5 (± 14.7) years (age range, 12 to 90 years). The patients were stratified into four age groups: younger than 50 years (n = 97); 50 to 59 years (n = 107); 60 to 69 years (n = 149); and 70 years or older (n = 177).

Measurements: For each patient, a dose-adjusted mean prothrombin time ratio was calculated by dividing the mean prothrombin time ratio by the mean daily warfarin dose.

Results: Older patients were more likely to be female (P < 0.001), to have more medical problems (P < 0.001), to be taking more medications (P < 0.001), and to weigh less than younger patients (P < 0.001). Across age groups, there were no significant differences in the use of medications that potentiated or inhibited the anticoagulant effects of warfarin. The prothrombin time ratio, when adjusted for dose, was significantly increased in older patients (P < 0.001). The increased anticoagulant response to warfarin seen with increasing patient age persisted even after simultaneously controlling for relevant demographic and clinical variables in a multivariate model. Other factors significantly associated with an increased sensitivity to warfarin included use of a medication with a potentiating interactive effect with warfarin, female gender, and overall medication use. Increased body weight and duration of warfarin use exceeding 6 months were found to be inversely related to anticoagulant response.

Conclusion: The anticoagulant response to warfarin is exaggerated with advancing age. This finding emphasizes the need for close monitoring of older patients treated with warfarin therapy.





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