A. Fib. Alternatives Are Edging Out Warfarin

Abstract

For decades, physicians and patients bemoaned the problems and inconveniences of warfarin to prevent strokes caused by atrial fibrillation. Finding the right dosage was hard and often turned out to be a moving target, patients needed regular coagulation monitoring, their anticoagulated state often fell out of the ideal range thereby putting them at an increased risk for either a stroke or bleeding complications, and care was needed with diet and other medications to avoid interactions that would throw off the whole delicate balance. A simpler, easier oral anticoagulant was what people wanted and what drove drug companies to try to find alternatives. The first of those, dabigatran, received Food and Drug Administration approval for stroke prevention in atrial fibrillation (AF) patients more than a year ago, in October 2010. The initial experience with AF management in a world with a warfarin alternative showed the eagerness of some physicians and patients to embrace a nonwarfarin, but also prompted the grudging recognition that warfarin has attractive features despite its flaws. Simple numbers show that dabigatran had a good first year. In late August 2011, Boehringer Ingelheim, the company that markets dabigatran (Pradaxa), reported that as of then, U.S. physicians had prescribed the drug to about 250,000 AF patients, roughly 10% of the total number of U.S. patients with AF. That level of market penetration beat expectations, considering that it represents a completely new treatment strategy, said Matthew Killeen, Ph.D., an analyst with Decision Resources in Burlington, Mass. On the other hand, dabigatran succeeded despite some widely acknowledged limitations, some of which have underscored warfarin’s strengths, starting with the issue of cost. The new, proprietary drug cost is in excess of $7 a day (although some pharmacies sell it for as low as about $4.50 per day), compared with an average wholesale price for warfarin of about $0.22 per day. “Cost is an issue with dabigatran. I’ve had patients tell me that they’ll stay with warfarin for another couple of years until the new drugs get less expensive,” said Dr. Gordon F. Tomaselli, professor of medicine and chief of cardiology at Johns Hopkins University in Baltimore. “I think there has been limited uptake of dabigatran primarily because of cost,” said Dr. Deepak L. Bhatt, chief of cardiology at the VA Boston Healthcare system and a cardiologist at Brigham and Women’s Hospital in Boston. But large copayments for new, more effective anticoagulants may fade as insurers realize that they can save more money in the long run by having beneficiaries treated with drugs that better prevent ischemic strokes and intracranial hemorrhages. The potential cost saving from cerebrovascular events avoided “will offset the increased drug cost,” Dr. Killeen asserted. Another issue that has made physicians think twice about prescribing dabigatran has been the gastrointestinal bleeds it triggers, a 6% rate of major gastrointestinal hemorrhages during each year of treatment, said Dr. Michael D. Ezekowitz, a professor of medicine at Jefferson Medical College, Philadelphia, and one of the researchers who led the clinical trials during dabigatran’s development. The Food and Drug Administration announced in December that it is looking into reports of serious bleeding events reported to the Adverse Events Reporting System and evaluated in November. But the agency acknowledged that determining whether the reported events are occurring more than with warfarin is problematic: “Because warfarin has been marketed for over 50 years and is well-known to cause bleeding, patients and healthcare professionals are not likely to report bleeding in association with warfarin.” The FDA reaffirmed its belief that “the benefits of Pradaxa continue to exceed the potential risks when the drug is used appropriately.”