November 7, 2012
Are New Drugs Viable Solution to Warfarin
Treatment Nonadherence?

Ontario—Treatment adherence can be less than optimal among older patients on warfarin therapy, according to a new research letter that questions whether newer anticoagulants would reduce discontinuation rates.

The study, reported in Archives of Internal Medicine, looked at continued use of the anticoagulant warfarin among a group of patients in Ontario, Canada. It noted that of the 125,195 patients who started warfarin therapy for atrial fibrillation (AF), 8.9% did not fill a second warfarin prescription during follow-up, 31.8% discontinued therapy within 1 year, and 43.2% discontinued within 2 years. By 5 years, the majority, 61.3%, had ended therapy.

The median time to discontinuation was 2.9 years, according to the study, and most likely to stop treatment were men, younger members of the study group, and those with lower stroke risk.

“The major challenges of warfarin therapy relate to poor adherence and persistence, the need for regular monitoring, and the risk of hemorrhage. In clinical trials, persistence with warfarin treatment ranges from 75% to 79% at 1 year, but persistence in clinical practice is thought to be poorer,” according to the authors who posit that their study may be the largest ever to examine adherence to warfarin therapy in an entire population.

They also suggest poor adherence might be a good argument for considering newer anticoagulants. Some of those—e.g., rivaroxaban (Xarelto, marketed by Janssen Pharmaceuticals), which is a direct factor Xa inhibitor, and dabigatran (Pradaxa, marketed by Boehringer Ingelheim), a direct thrombin inhibitor—have FDA approval in the United States for some indications. Others are in use in Europe and elsewhere, but still awaiting FDA approval.

“These findings highlight the importance of considering recent, real-world estimates of warfarin therapy persistence, particularly when comparing warfarin to newer anticoagulants that also carry a risk of hemorrhage yet require no routine monitoring,” the authors write.

Researchers used linked administrative databases in Ontario to identify all residents 66 and older who were newly prescribed warfarin for atrial fibrillation between April 1, 1997, and March 31, 2008. All had health insurance coverage for prescription drugs.

A related commentary suggests that the lack of specialized anticoagulation clinics could be contributing to the high rates of nonadherence. In one analysis, the authors point out, Canada was reported to have 5% of patients being treated at structured anticoagulation clinics compared with 25% of patients in the U.S. and 100%, in The Netherlands. The commentators also point out that some studies have suggested that the new drugs have no better adherence history than warfarin.

The bigger issue, they say, is to find out why warfarin therapy was discontinued.
“When used appropriately, oral anticoagulation therapy has been shown to decrease the incidence of cardioembolic stroke in patients with AF by 50% to 60%. Appropriate use of warfarin anticoagulation requires precise adherence and monitoring to optimize the risk to benefit ratio associated with therapy and to ensure that therapy can be safely continued throughout the prescribed duration,” they explain, adding, “Appropriateness of anticoagulation is perhaps a more important outcome to evaluate rather than absolute discontinuation rates…”

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