Margaret C. Fang, MD, MPH; Yuchiao Chang, PhD; Elaine M. Hylek, MD, MPH; Jonathan Rosand, MD; Steven M. Greenberg, MD, PhD; Alan S. Go, MD; Daniel E. Singer, MD
Acknowledgments: The authors thank Susan Regan, PhD, for her invaluable assistance with the Anticoagulation Management Services database; Robert A. Hughes, MD, and Walter J. Moulaison Jr., RN, MSN, MBA, directors of the Massachusetts General Hospital Anticoagulation Management Services, for facilitating research using the unit; and Drs. Shawn Murphy and Henry Chueh and the Partners Health Care Research Patient Data Registry group for facilitating use of their database.
Grant Support: By National Research Service Award 5T32-HP-11001-14, Public Health Services research grant AG15478 from the National Institute on Aging, and the Eliot B. Shoolman Fund of the Massachusetts General Hospital.
Potential Financial Conflicts of Interest: Honoraria: E.M. Hylek (Bristol-Myers Squibb); Grants received: E.M. Hylek (Bristol-Myers Squibb), D.E. Singer (DuPont Pharma).
Requests for Single Reprints: Margaret C. Fang, MD, MPH, Division of General Internal Medicine, Hospitalist Group, University of California, San Francisco, 533 Parnassus Avenue, Box 0131, San Francisco, CA 94143; e-mail, email@example.com.
Current Author Addresses: Dr. Fang: Division of General Internal Medicine, Hospitalist Group, University of California, San Francisco, 533 Parnassus Avenue, Box 0131, San Francisco, CA 94143.
Drs. Chang, Hylek, and Singer: General Medicine Division, Clinical Epidemiology Unit, Massachusetts General Hospital, 50 Staniford Street, 9th Floor, Boston, MA 02114.
Drs. Rosand and Greenberg: Neurology Clinical Trials Unit, Massachusetts General Hospital, ACC-836, 15 Parkman Street, Boston, MA 02114.
Dr. Go: Division of Research, Kaiser Permanente of Northern California, 2000 Broadway Street, 3rd Floor, Oakland, CA 94612.
Author Contributions: Conception and design: M.C. Fang, E.M. Hylek, D.E. Singer.
Analysis and interpretation of the data: M.C. Fang, Y. Chang, A.S. Go, D.E. Singer.
Drafting of the article: M.C. Fang, D.E. Singer.
Critical revision of the article for important intellectual content: E.M. Hylek, J. Rosand, S.M. Greenberg, A.S. Go, D.E. Singer.
Final approval of the article: E.M. Hylek, J. Rosand, S.M. Greenberg, A.S. Go, D.E. Singer.
Provision of study materials or patients: J. Rosand, S.M. Greenberg.
Statistical expertise: Y. Chang, D.E. Singer.
Obtaining of funding: D.E. Singer.
Administrative, technical, or logistic support: D.E. Singer.
Collection and assembly of data: M.C. Fang
The risk for atrial fibrillation–associated stroke increases at low anticoagulation intensities. However, higher intensities increase hemorrhage risk. Optimal use of warfarin for atrial fibrillation requires precise information on the risk for intracranial hemorrhage as a function of patient age and anticoagulation intensity.
To examine the relationship of age, anticoagulation intensity, and risk for intracranial hemorrhage.
Academic medical center.
170 case-patients who developed intracranial hemorrhage during warfarin therapy and 1020 matched controls who did not; both case-patients and controls were taking warfarin for atrial fibrillation.
The authors performed multivariable conditional logistic regression to determine the odds of intracranial hemorrhage with regard to age and international normalized ratio (INR), controlling for comorbid conditions and aspirin use.
Case-patients were older than controls (median age, 78 years vs. 75 years; P < 0.001) and had higher median INRs (2.7 vs. 2.3; P < 0.001). The risk for intracranial hemorrhage increased at 85 years of age or older (adjusted odds ratio, 2.5 [95% CI, 1.3 to 4.7]; referent age, 70 to 74 years) and at an INR range of 3.5 to 3.9 (adjusted odds ratio, 4.6 [CI, 2.3 to 9.4]; referent INR, 2.0 to 3.0). The risk for intracranial hemorrhage at INRs less than 2.0 did not differ statistically from the risk at INRs of 2.0 to 3.0 (adjusted odds ratio, 1.3 [CI, 0.8 to 2.2]).
Although duration of anticoagulation has been associated with hemorrhage in other studies, the current study could not control for this potential confounder.
The risk for intracranial hemorrhage increases at age 85 years. International normalized ratios less than 2.0 were not associated with lower risk for intracranial hemorrhage compared with INRs between 2.0 and 3.0. Therefore, anticoagulation management should focus on maintaining INRs in the 2.0 to 3.0 range, even in elderly patients with atrial fibrillation, rather than targeting INRs less than 2.0. Similarly, INRs of 3.5 or greater should be avoided.
Fang MC, Chang Y, Hylek EM, Rosand J, Greenberg SM, Go AS, et al. Advanced Age, Anticoagulation Intensity, and Risk for Intracranial Hemorrhage among Patients Taking Warfarin for Atrial Fibrillation. Ann Intern Med. ;141:745–752. doi: 10.7326/0003-4819-141-10-200411160-00005
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Published: Ann Intern Med. 2004;141(10):745-752.
Cardiology, Neurology, Rhythm Disorders and Devices.
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