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The Risk for and Severity of Bleeding Complications in Elderly Patients Treated with Warfarin

Stephan D. Fihn, MD, MPH; Catherine M. Callahan, MS; Donald C. Martin, PhD; Mary B. McDonell, MS; Jorja G. Henikoff, MS; and Richard H. White, MD
[+] Article and Author Information

For The National Consortium of Anticoagulation Clinics* *For a complete listing of study participants, see the Appendix. Acknowledgments: The authors thank Frits Rosendaal and Suzanne Cannegieter for their thoughtful comments on the manuscript. Grant Support: In part by grants IIR 87-063 and IIR 90-036 from the Health Services Research and Development Program of the Department of Veterans Affairs and by unrestricted educational grants from Boehringer-Mannheim, Inc., and Du Pont Pharma. Requests for Reprints: Stephan D. Fihn, MD, MPH, Northwest Veterans Affairs Health Services Research and Development Field Program152, Veterans Affairs Puget Sound Healthcare System, 1660 South Columbian Way, Seattle, WA 98108. Current Author Addresses: Drs. Fihn and Martin and Ms. Callahan, Ms. McDonell, and Ms. Henikoff: Northwest Veterans Affairs Health Services Research and Development Field Program152, Veterans Affairs Puget Sound Healthcare System, 1660 South Columbian Way, Seattle, WA 98108.


Copyright ©2004 by the American College of Physicians


Ann Intern Med. 1996;124(11):970-979. doi:10.7326/0003-4819-124-11-199606010-00004
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Objective: To determine whether increasing age is associated with an increased risk for bleeding during warfarin treatment.

Design: Combined retrospective and prospective cohort studies.

Setting: 6 anticoagulation clinics.

Patients: 2376 patients receiving warfarin for various indications.

Measurements: Bleeding events categorized as minor (resulting in no costs or consequences), serious (requiring testing or treatment), life-threatening, or fatal.

Results: 812 first bleeding events (4 fatal, 33 life-threatening, 222 serious, and 553 minor) occurred during 3702 patient-years. Age was inversely related to the mean warfarin dose and dose-adjusted prothrombin time ratio. The unadjusted incidence of minor bleeding complications did not vary according to age group: 18.0 per 100 patient-years for patients younger than 50 years of age, 21.5 for patients 50 to 59 years of age, 24.0 for patients 60 to 69 years of age; 23.5 for patients 70 to 79 years of age, and 16.3 for patients 80 years of age and older. The unadjusted incidence of serious bleeding complications also did not vary according to age group: 9.3 per 100 patient-years for patients younger than 50 years of age, 7.1 for patients 50 to 59 years of age, 6.6 for patients 60 to 69 years of age, 5.1 for patients 70 to 79 years of age, and 4.4 for patients 80 years of age and older. The unadjusted incidence of life-threatening or fatal complications combined was significantly higher among the oldest patients: 0.75 per 100 patient-years for patients younger than 50 years of age, 0.97 for patients 50 to 59 years of age, 1.10 for patients 60 to 69 years of age, 0.68 for patients 70 to 79 years of age, and 3.38 for patients 80 years of age and older. Patients 80 years of age and older had a relative risk of 4.5 (95% CI, 1.3 to 15.6) compared with patients younger than 50 years of age. After adjustment for the intensity of anticoagulation therapy and the deviation in the prothrombin time ratio using Cox and Poisson regression, age was not generally associated with the occurrence of bleeding; relative risk estimates ranged from 0.99 to 1.03 per year of age (lower-bound 95% CI, 0.97 to 1.01; upper-bound 95% CI, 1.00 to 1.09). The single exception was life-threatening and fatal complications in patients 80 years of age or older (relative risk, 4.6 [CI, 1.2 to 18.1]).

Conclusions: Age did not appear to be an important determinant of risk for bleeding in patients receiving warfarin, with the possible exception of age 80 years or older. The intensity of anticoagulation therapy and the deviation in the prothrombin time ratio were much stronger predictors of risk for bleeding.

Figures

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Figure 1.
Adjusted relative risks for bleeding complications and 95% Cls according to age category.

Relative risks were obtained by Cox regression using combined retrospective and prospective cohorts with adjustment for intensity of warfarin therapy and deviation in prothrombin time ratio.

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