Use of Anticoagulation in Elderly Patients with Atrial Fibrillation Who Are at Risk for Falls

Candice L Garwood, PharmD BCPS; Tia L Corbett, PharmD


The Annals of Pharmacotherapy. 2008;42(4):523-532. 

In This Article

Risk of Intracranial Hemorrhage with Antithrombotic Therapy

Concern over the potential risk of bleeding, in particular ICH, with warfarin therapy has limited its use in elderly patients with AF. Major risk factors for ICH are advanced age, hypertension, anticoagulation intensity, and previous cerebral ischemia.[12,44] Studies have found an intolerable rate of ICH in elderly patients with uncontrolled hypertension.[12,33] However, modest decreases in blood pressure greatly decrease the risk of ICH.[45] In contrast to ICH, hypertension does not appear to be linked with warfarin-associated SDH. Head trauma is the most notable risk factor for SDH.[46]

While ICH is the worst possible adverse effect of warfarin, aspirin is not without risk. Some data suggest that the rates of ICH and SDH between well-managed warfarin and aspirin therapy may be comparable.[25,26,47,48] Estimated rates of primary ICH in patients taking aspirin and warfarin (INR 2.5) are 0.2% per year and 0.3-0.6% per year, respectively.[44] The incidence of ICH is directly related to INR intensity and dramatically increases above an INR of 3.5.[44,49,50,51] INR values less than 2.0 are not associated with lower rates of ICH when compared with a range of 2.0-3.0.[44,52] Several AF studies exhibited similar rates of ICH in patients taking warfarin versus aspirin. The SPINAF (Stroke Prevention in Non-Valvular Atrial Fibrillation) trial was a randomized, double-blind, placebo-controlled study that showed no difference in ICH with warfarin when compared with placebo. The trial had a lower therapeutic INR limit of 1.4, but its upper limit of 2.8 was well into the current recommended therapeutic goal.[28] EAFT compared a vitamin K antagonist, aspirin, and placebo and found that the annual incidence of ICH was quite low (0.2% per year with aspirin, 0.1% per year with placebo, 0% per year with a vitamin K antagonist).[26] Interestingly, there was no ICH in the vitamin K antagonist group, regardless of the high INR target range of 2.5-4.0. Bleeding rates in the BAFTA study, including ICH, were no different between aspirin (2.0% per year) and warfarin (1.9% per year) (RR 0.96; 95% CI 0.53 to 1.75; p = 0.90).[25] The INR goal for this trial was 2.0-3.0. There was high crossover between the aspirin and warfarin groups, yet these data are interesting, as the population studied was older than 75 years of age. The SPAF II trial, a randomized trial of adjusted-dose warfarin versus aspirin, did show more ICH in warfarin patients greater than 75 years of age (1.8% per year with warfarin vs 0.8% per year with aspirin; no p value reported).[33] However, the higher level of INR intensity (4.5) and hypertension are thought to have been contributors to these bleeding episodes.

The Japanese Nonvalvular Atrial Fibrillation-Embolism Secondary Prevention trial assessed secondary stroke prevention by comparing low-dose and adjusted-dose warfarin.[23] The investigators found a higher major bleeding rate in the adjusted-dose warfarin group with an INR 2.2-3.5 (6.6% per year with adjusted-dose warfarin vs 0% per year with low-dose warfarin; p = 0.0103). Included in the major bleeding rates was ICH (1.1% vs 0% per year, respectively; no p value reported). These findings were the antithesis of the bleeding rates identified in the aforementioned studies; however, this trial had relatively few patients, and it is possible that there was a racial difference, as ICH rates are known to be higher in the Japanese population. The limitations of this trial and the SPAF II trial should be considered when assessing ICH risk.

There is a narrow margin of safety when treating patients with warfarin. An INR goal of 2.0-3.0 should be the standard of practice for elderly patients with AF when warfarin is indicated. Lower target goals do not minimize risk of ICH. Decreasing modifiable ICH risk factors, such as treating hypertension, can greatly enhance the safety of warfarin's use. However, treatment with aspirin does not appear to be a benign alternative to warfarin in the attempt to decrease the rate of ICH.


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