Although newer anticoagulants have been developed for preventing stroke in atrial fibrillation, many patients will still receive warfarin, which carries a low residual stroke risk, a meta-analysis showed.

In a pooled analysis of randomized controlled trials from the past decade, the remaining risk of stroke or systemic embolism in patients taking warfarin was 1.66% per year, Venu Menon, MD, of the Cleveland Clinic, and colleagues reported online in Archives of Internal Medicine.

That pooled event rate is lower than the one observed in a previous meta-analysis of trials comparing warfarin and placebo that were conducted from 1989 to 1993 (2.09% per year).

The improved rate is at least partly related to greater time spent in the therapeutic international normalized ratio (INR) range of 2.0 to 3.0. Only two of the six earlier studies had a time spent in the therapeutic range of 60% or more, compared with seven of the eight more current studies. The authors noted that improved control of other risk factors, including hypertension and dyslipidemia, was also responsible for some of the lower stroke risk. “These results could potentially aid the decision process for warfarin therapy for individual physicians and allow health systems to evaluate the cost efficacy of adopting newer agents universally or in specific high-risk clinical subsets,” they wrote. “Even after consideration of the costs associated with regular INR testing, in most settings, the overall cost of therapeutic strategies using these newer agents will exceed the costs of comparative strategies incorporating generic warfarin,” they said. Thus, they said, many patients will continue to take warfarin because of cost concerns. New oral anticoagulants have performed well in recent trials when compared with warfarin, showing either comparable or superior efficacy for preventing stroke in patients with atrial fibrillation without the need for regular blood tests. The new agents, however, will be more expensive and many patients - especially if they live in areas with limited resources - will continue to use warfarin. To evaluate the residual stroke risk with warfarin in contemporary trials comparing the drug to other thromboprophylaxis strategies, Menon and colleagues pooled data from eight randomized trials that included 32,053 patients. All were conducted from 2001 to 2011. Across the warfarin arms of the trials, the time spent in the therapeutic range varied from 55% to 68%, and the annual rate of stroke or systemic embolism ranged from 1.2% to 2.3%. Major bleeding rates varied from 1.4% to 3.4% per year. The pooled intracranial hemorrhage rate was 0.61% per year. The residual risk of stroke among warfarin-treated patients was significantly higher in patients 75 and older, females, those with a history of stroke or transient ischemic attack, and those with no previous exposure to vitamin K antagonists (P<0.05 for all). The rate of stroke also increased with higher CHADS2 (congestive heart failure, hypertension, age, diabetes, and prior stroke) scores. In an accompanying editorial, Daniel Singer, MD, of Massachusetts General Hospital in Boston, and Alan Go, MD, of Kaiser Permanente Northern California in Oakland, acknowledged the advantages of the newer anticoagulants over warfarin but also pointed out some risks. Adherence may suffer without the constant monitoring required for warfarin therapy, which could be exacerbated by the higher costs of the new drugs, they wrote. In addition, patient education may suffer and physicians may become less vigilant, particularly when it comes to checking renal function. Although Singer and Go said that they could not provide detailed guidance about who should be taking a novel anticoagulant in their brief editorial, they said that "patients who are comfortable with warfarin therapy and whose time in therapeutic range is above 75% should be in no hurry to switch." Such patients "may forgo a small reduction in risk of intracranial hemorrhage, but they should benefit as we gain more experience with the novel agents," they wrote. "For others, the case for the use of novel anticoagulants may be more compelling, particularly if out-of-pocket costs are acceptable."