Novel oral anticoagulants have outstripped warfarin for usage in the U.S., but at a price. A study found that the three new options for treating patients with atrial fibrillation made up 62 percent of new prescriptions but cost $900 higher than warfarin after six months.

Dabigatran (Pradaxa, Boehringer Ingelheim), a direct thrombin inhibitor, was approved by the FDA in October 2012 to reduce the risk of stroke in patients with nonvalvular atrial fibrillation. In November 2011, rivaroxaban (Xarelto, Janssen Pharmaceuticals/Bayer HealthCare), became the second approved anticoagulant followed by apixaban (Eliquis, Bristol-Myers Squibb and Pfizer) in December 2012. The latter two drugs are Factor Xa inhibitors.

Nihar R. Desai, MD, of Brigham and Women’s Hospital in Boston, and colleagues wanted to explore the usage of the three novel oral anticoagulants since their approvals. To do so, they accessed nationwide medical and prescription claims for patients covered by the insurer Aetna who had a new diagnosis of nonvalvular atrial fibrillation between Oct. 1, 2010 and June 30, 2013.

The data included procedures, physician visits, hospitalizations and filled prescriptions as well as clinical information such as CHADS₂ and HAS-BLED scores. Desai and colleagues used the date of the patient’s first filled prescription for warfarin or one of the three other anticoagulants as the index date for the study.

The 6,893 patients in the study had a mean age of 61.3 years and mean CHADS₂ and HAS-BLED scores of 1.7 and 2, respectively. The group was predominantly male.

Over the entire study period, 57.7 percent of the prescriptions filled were for warfarin, followed by dabigatran (32.8 percent), rivaroxaban (9.3 percent) and apixaban (0.1 percent). But warfarin lost its dominance over time. By June 2013, 62 percent of patients received one of the novel oral anticoagulants.

Dabigatran, which was first to market, accounted for 44 percent of patients by November 2011, which dropped to 15 percent a year later. By January 2013, rivaroxaban surpassed dabigatran and had the most users of all the options by the end of the study period. Two percent of patients were prescribed apixaban six months after its approval.

Desai et al noted that dabigatran’s decline coincided with reports of increased risk of MI and serious and fatal bleeding associated with the drug. They also pointed out that rivaroxaban requires one dose a day rather than dabigatran’s twice daily dosing, which might be a factor.

The patients prescribed novel oral anticoagulants tended to be younger, healthier with lower CHADS₂ and HAS-BLED scores compared with warfarin users. For instance, 46 percent of patients with CHADS₂ scores started novel anticoagulants compared with 39 percent with scores of 2 and 26 percent with scores of 3. Lower CHADS₂, Cha₂DS-VASC and HAS-BLED scores and higher household incomes were predictors of initiation of novel anticoagulants, and women were less likely to be prescribed them than were men.  

“The greatest absolute benefit from novel anticoagulants has been shown to be among patients at highest baseline risk for stroke or systemic embolism, which is at odds with our observation of selection of seemingly lower risk patients for these drugs,” they wrote. “Such a finding may reflect provider conservatism for new drug adoption, particularly given longitudinal experience with warfarin.”

Warfarin cost the insurer and patients much less than the three new drugs. Patients paid on average $54 for six months of warfarin vs. $205 for dabigatran and $221 for rivaroxaban. Insurers picked up tabs on average of $68, $852 and $865, respectively.

“Novel anticoagulants have only recently attainted greater than 50% of market share, yet have accounted for more than 90% of insurer spending on anticoagulants since the introduction of dabigatran in 2010,” they wrote. “A six-month difference in total costs of $900 in our cohort translates into billions of dollars at a national level.”

They recommended continued scrutiny of use patterns to identify the potential of patient selection bias. They also cautioned that observational studies should consider differences in comorbidities between users of warfarin and the new anticoagulants.  

The study was published online May 20 in the American Journal of Medicine.