Intracranial hemorrhage, atrial fibrillation, and the elderly

In this issue, Drs. Fang and Singer (page 24) summarize their case-control study examining the risk of intracranial hemorrhage in patients taking warfarin (Coumadin). The authors investigated risk factors for the development of intracranial hemorrhage. They then questioned whether low-intensity anticoagulation therapy would reduce the risk of intracranial hemorrhage in elderly patients. Their study included 170 patients who developed intracranial hemorrhage while receiving warfarin therapy between 1993 and 2002. Of these patients, 145 had international normalized ratio (INR) data and were included in the analysis. They were compared with 1,020 matched control patients who were taking warfarin but did not have intracranial hemorrhage. They found that the risk of intracranial hemorrhage was significantly increased in patients aged 85 years or older. After adjusting for age, an INR above 3.5 was noted to be a significant risk factor. A reduced INR surprisingly did not decrease the risk of intracranial hemorrhage.

The most devastating complication of atrial fibrillation is a thromboembolic event leading to a cerebrovascular accident. Of all ischemic strokes, 15% are due to cardiogenic emboli (75,000 cases per year); 45% of cardiogenic emboli in the United States are due to nonvalvular atrial fibrillation. The risk of stroke in patients with atrial fibrillation is five to seven times greater than in control patients.1-5 The stroke rate in patients with lone atrial fibrillation appears to be about 1.6% among those aged 60 to 69 years, 2.1% for those aged 70 to 79 years, and 3.0% for those older than 80 years.6 There appears to be no difference in stroke rate for patients with chronic persistent versus paroxysmal atrial fibrillation.6 Previous trials have identified several risk factors for thromboembolism during atrial fibrillation. In an analysis of data pooled from five major randomized clinical trials, it appears that increasing age, previous stroke or transient ischemic attack, history of hypertension, and history of diabetes are all independent risk factors for stroke due to atrial fibrillation.6 In an analysis of the Stroke Prevention in Atrial Fibrillation (SPAF) study, congestive heart failure was also identified as a significant risk factor, as were left ventricular dysfunction and left atrial enlargement as shown on two-dimensional echocardiography.7,8

Drs. Fang and Singer correctly pointed out that many physicians are hesitant to prescribe warfarin for their elderly patients. The Cardiovascular Health Study, a population-based longitudinal study of risk factors for coronary disease and stroke in 5,201 men and women aged 65 years and older, found that, despite a relatively high prevalence of atrial fibrillation in elderly patients (as high as 9.1% in men and women with coexisting clinical cardiovascular disease), 62% of patients for whom warfarin was indicated received neither warfarin nor aspirin.9 In a retrospective analysis of 95 patients discharged from the hospital with a diagnosis of atrial fibrillation, 48% of those in whom warfarin was indicated received neither warfarin nor aspirin.10 This finding is particularly surprising because long-term anticoagulation therapy has been confirmed to reduce the risk of stroke in atrial fibrillation in multiple large randomized trials. Furthermore, the current study confirms that low-dose anticoagulation therapy is not effective in preventing thromboembolic events. In the SPAF III trial, 1,044 patients with chronic atrial fibrillation and at least one risk factor for thromboembolic events were randomly assigned to receive low-intensity, fixed-dose warfarin plus aspirin versus adjusted-dose warfarin (INR, 2.0—3.0). Results showed an ischemic stroke and systemic embolism rate of 7.9% per year in the combination group versus 1.9% in the adjusted-dose group (P < .001).11

Despite the overwhelming data in support of long-term warfarin use in patients suffering from chronic persistent, permanent, and paroxysmal atrial fibrillation, the drug is widely underused. The current study firmly addresses the risk of intracranial hemorrhage, which is often an excuse for not offering anticoagulation therapy to elderly patients. Despite the increased risk of hemorrhage, elderly patients also have an increased risk of stroke. To quote the authors, “the incidence rate of ischemic stroke in those not receiving warfarin far exceeds the rate of intracranial hemorrhage in those taking warfarin.” This study adds support to the use of warfarin in elderly patients, who are the patients with the highest risk of stroke from atrial fibrillation.