New Anticoagulants May Give Warfarin a Run for Its Money

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Atrial fibrillation (AF) soaks up $26 billion in the U.S. annually. This figure is only set to rise. The estimated three million AF patients in the U.S. likely will double in the next 25 years (Circ Cardiovasc Qual Outcomes, online May 3, 2011). Most physicians turn to warfarin as the drug of choice to prevent stroke in the AF population, but now that novel therapeutics like dabigatran and rivaroxaban are available, will warfarin continue to own the U.S. anticoagulant market?

For years, warfarin has been the lone wolf on the anticoagulant market, but recently agents such as dabigatran (Pradaxa, Boehringer Ingelheim), rivaroxaban (Xarelto, Bayer/Johnson & Johnson) and apixaban (Eliquis, Bristol-Myers Squibb) have entered as competition, and may be poised to give warfarin a run for its money. While warfarin has a multitude of shortcomings—a narrow therapeutic window, a shorter half-life, frequent International Normalized Ratio (INR) checks and numerous food-drug interactions—it works. In fact, warfarin has been shown to reduce stroke by almost 62 percent when compared with placebo (Ann Intern Med 1999;131:492-501).

“It’s always good to have choices,” says Sanjay Kaul, MD, MPH, director of the fellowship training program in cardiovascular diseases at the Cedars-Sinai Medical Center in Los Angeles. But clinicians may be more apt to stick with prescribing the familiar drug, unless a patient cannot tolerate it.

Warfarin: Is it here to stay?

While warfarin has limitations, it is cheap and many patients have positive outcomes on the drug. So, when should a clinician switch a patient over to dabigatran or rivaroxaban?

“If a patient with known AF presents to me in a stable fashion on warfarin, I’m not in a  hurry to switch him or her to a newer agent,” Jeffrey I. Weitz, MD, deputy chair of research at McMaster University in Hamilton, Ontario, says. “However, if the patient’s INR is erratic or unstable on warfarin, then he or she would be a good candidate for a newer agent.”

Strategies for the new AF patient are more difficult, notes Mintu P. Turakhia, MD, cardiac electrophysiologist at Stanford Hospital & Clinics and director of cardiac electrophysiology at Palo Alto VA Healthcare System in California. “For a patient already on warfarin, it becomes a challenge because we are making inferences about anticoagulation control and how it compares to other agents across patient populations,” Turakhia offers. Data suggest that patients with poor INR would have fewer safety events (less bleeding and stroke) on either rivaroxaban or dabigatran; however, it remains unclear how compliant patients will be with these once-daily or twice-daily doses.  

Currently, with the help of CHADS2 scores, clinicians can make a better decision as to whom to place on specific treatment strategies and in whom to tailor treatment to the individual patient. In a substudy of the RE-LY trial, Oldgren et al found higher CHADS2 scores to be linked to increased rates of stroke, systemic embolism, bleeding and mortality in AF patients who received anticoagulants (Ann Intern Med 2011;155:660-667). Of the 18,112 AF patients in RE-LY who received oral anticoagulants, those who had a CHADS2 score between 3 and 6 had a higher risk of experiencing a primary endpoint compared with those who had a CHADS2 score between 0 and 1, 2.24 percent vs. 0.93 percent, respectively. Now, CHADS2 scores can identify who might benefit from a more complex treatment or benefit from aspirin alone.

“It is time to consider, where possible, switching patients over to the newer anticoagulants,” Justin A. Ezekowitz, MD, director of the Heart Function Clinic at the University of Alberta Hospital in Canada, says. “It also comes down to patient preference. Some patients are comfortable on the same drug [warfarin] they have been on for years and managed well.”

While Ezekowitz says that there is much known about warfarin use in complicated patients or high-risk groups, the same can’t be said for these newer agents that have far less exposure in the clinical setting. “In these settings, clinicians may be a little gun shy to prescribe newer agents,” he notes.

“However, the time has come to consider what is best for patients and this may include the use of these drugs as a first-line treatment, which might include switching patients even if they are tolerating warfarin well,” he says.

At TCT.11, Matthew R. Reynolds, MD, MSc, of the health economics and technology assessment research group at