Abstract & Commentary
Synopsis: Maintaining INRs (International normalized ratios) between 2 and 3 is safer than INRs below 2, as suggested by some guidelines.
Source: Fang MC, et al. Ann Intern Med. 2004;141:745-752.
Atrial fibrillation is a common event in the older population. Intracranial hemorrhage is the most dangerous complication of warfarin therapy because of its high risk for death and severe neurological complications. However, fear of hemorrhage may prevent some physicians from prescribing anticoagulation. Recent guidelines recommend using lower intensity anticoagulation for the prevention of stroke in patients older than 75 years of age who have atrial fibrillation.1 These guidelines recommend INRs of 1.6 to 2.5.
The objective of this study was to examine the relationship of age, anticoagulation intensity, and the risk of intracranial hemorrhage. It was a case-controlled study involving 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.
Fang et al performed statistical analysis to determine the odds of intracranial hemorrhage with regard to age and INRs, 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 significantly higher INRs (2.7 vs 2.3). The risk of intracranial hemorrhage increased at 85 years of age or older, (odds ratio 2.5), and at an INR range of 3.5 to 3.9, (odds ratio 4.6).
The risk for intracranial hemorrhage at INRs of less than 2 did not differ from INRs of 2 to 3. Conclusion: The risk of intracranial hemorrhage increases at age 85. INR ratios of less than 2 were not associated with lower risk for intracranial hemorrhage compared to INRs in the 2 to 3 range. Therefore, anticoagulation should focus on maintaining INRs in the 2 to 3 range, even in older patients with atrial fibrillation. Similarly, INRs of 3.5 or greater should be avoided.
Comment by Ralph R. Hall, MD, FACP
Fang and colleagues note the limitations of this study. The case-controlled design may have resulted in a selection bias and, in contrast to controls, many of the case-patients were not followed in the same clinic, and differences in patient characteristics, anticoagulation management, and monitoring may have biased some of the risk estimates. Further, the difficulties in controlling aspirin intake data are always a problem in that patients may not accurately report the frequency or dose of aspirin. In this study it was reported that approximately 20% of the patients in each group took aspirin. Nevertheless, this is a compelling study and offers new guidelines in the management of atrial fibrillation in older patients.
It is of note that the contrasting guidelines for the management of older patients with atrial fibrillation by other organizations referenced by Fang and colleagues, is from the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee on Practice Guidelines. These guidelines were published in 2001.1 It is hoped that these organizations will review this study and other new data and republish their guidelines soon.
It goes without saying that one of the most important aspects of managing anticoagulation is the precise education and monitoring of the patients.
Dr. Hall, Emeritus Professor of Medicine University of Missouri- Kansas City School of Medicine, is Associate Editor of Internal Medicine Alert.
1. Foster V, et al. J Am Coll Cardiol. 2001;38:1231-1266.