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Dabigatran has been readily integrated into clinical practice in the United States, primarily for treatment of atrial fibrillation (A-fib) but increasingly for off-label indications as well, according to a study published online September 4, 2012, ahead of print in Circulation: Cardiovascular Quality and Outcomes. However, researchers found no evidence to prove that the widespread undertreatment of A-fib has changed since the new anticoagulant’s introduction.

In October 2010, the US Food and Drug Administration approved dabigatran (Pradaxa, Boehringer Ingelheim Pharmaceuticals, Ridgefield, CT) for the reduction of stroke and systemic embolism in patients with nonvalvular A-fib.

For the study, Caleb Alexander, MD, MS, of Johns Hopkins Bloomberg School of Public Health (Baltimore, MD), and colleagues analyzed data on oral anticoagulant use and expenditures from the National Disease and Therapeutic Index, an ongoing physician survey conducted by IMS Health (Collegeville, PA), between 2007 and 2011. The investigators looked specifically at office visits involving oral anticoagulation.

Dabigatran Gains Ground

Over the study period, warfarin treatment visits declined from about 2.1 million per quarter in 2007 to roughly 1.6 million per quarter in 2011. Conversely, the number of quarterly visits when dabigatran was used increased from about 62,000 in late 2010 to about 363,000 in late 2011. This increase in dabigatran treatment reflected a 15.8% rise in its market share of oral anticoagulation visits (from 3.1% to 18.9%).

Most patients treated fell within the ages of 65 to 84 years, and dabigatran was more often used in this cohort than warfarin. Still, 6.7% of dabigatran use and 12.7% of warfarin use was seen in older patients during 2011.

The proportion of warfarin use dedicated specifically to preventing stroke in A-fib remained constant over the study period at around 41%. Although 92% of dabigatran usage was related to A-fib in late 2010, on-label usage decreased to 63% by late 2011. The most common off-label uses of dabigatran were for CAD, hypertensive heart disease, and venous thromboembolism.

In late 2010, about 60.5% of A-fib visits involved warfarin. By late 2011, this proportion decreased to 44.4% while the share of A-fib visits treated by dabigatran increased from 4.0% to 16.9% over the same period. Looking at all A-fib visits where an oral anticoagulant was used, the prevalence of dabigatran increased from 6.7% to 27.5%.

Yet reliance on antiplatelet monotherapy for A-fib remained constant at 4.6% over the study period, and the percentage of visits reporting neither anticoagulant nor antiplatelet medication held steady at about 35% since 2010.

Warfarin sales remained stable with about 8.8 million quarterly prescriptions in 2007 to 2010 and 8.3 million in late 2011. On the other hand, dabigatran sales increased tenfold from 73,000 prescriptions in the last quarter of 2010 to 733,000 by late 2011, amounting to a rise in market share from 0.8% to 8.1%. Total warfarin expenditures decreased slightly from about $169 million per quarter in 2007 to $158 million in 2010, and finally to $144 million in 2011. In contrast, quarterly dabigatran expenditures rose from $16 million in late 2010 to $166 million in late 2011.

Convenience Not the Only Consideration

“Our findings are important considering the increasing prevalence of thromboembolic disease in the United States, as well as the costs that are incurred and the complexity of its management,” Dr. Alexander and colleagues write. “The new oral anticoagulants such as direct thrombin inhibitors and activated factor X inhibitors have the potential to substantially alter its therapeutic landscape.”

However, the extent to which these new therapies will be used is dependent on several issues, the researchers say. “Dabigatran, rivaroxaban, and other similar agents offer greater dosing convenience and fewer drug-drug interactions,” they observe. “These benefits must be weighed against greater costs for payers, providers, and patients, as well as uncertainties regarding their comparative safety and effectiveness, which have yet to be rigorously established beyond the clinical trials used to gain their market approval.”

Dabigatran seems “particularly cost-effective” for high-risk stroke patients and for those who are not easily managed on warfarin, the investigators write. “If new warfarin monitoring methods, such as less frequent laboratory assessments, are shown to be safe and effective, this cost-effectiveness comparison may shift, especially given recent evidence of significant improvement in the proportion of time spent in therapeutic anticoagulation among warfarin users and subsequent decline in the incidence of stroke.”

 Off-Label Usage ‘High’

In a telephone interview with TCTMD, Larry B. Goldstein, MD, of Duke University Medical Center (Durham, NC), expressed surprise at the “high” off-label use of dabigatran.

Dr. Goldstein, who co-chaired the writing committee for the 2011 American Heart Association/American Stroke Association stroke prevention guidelines, advised waiting to learn about possible drug interactions before using a new medication for an off-label purpose.

Moreover, he added, “exactly how this is going to play out in the real world is not straightforward [given the lack of comparative data between dabigatran and other new anticoagulants like rivaroxaban]. Right now we don’t have a way of assessing how well these drugs are working, at least not in the acute setting.”

The current study is itself limited, Dr. Goldstein noted, because it does not report contraindications that might have affected choice of anticoagulant therapy.

Source:

Kirley K, Qato DM, Kornfield R, et al. National trends in oral anticoagulant use in the United States, 2007 to 2011. Circ Cardiovasc Qual Outcomes. 2012;Epub ahead of print.

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