Physicians in ambulatory practices have embraced the anticoagulant dabigatran, with cardiologists leading the charge, according to a study published in the September issue of Circulation: Cardiovascular Quality and Outcomes. The direct thrombin inhibitor was prescribed primarily for atrial fibrillation (AF), and it was increasingly used off-label. Nonetheless, AF undertreatment persisted.

The FDA approved dabigatran (Pradaxa, Boehringer Ingelheim) in October 2010 for the prevention of stroke in patients with nonvalvular atrial fibrillation. Approval hinged in part on results from the RE-LY trial, which found that dabigatran at a 110 mg dose was associated with similar rates of stroke and systemic embolism as warfarin and lower rates of major hemorrhage; at the higher 150 mg dose, dabigatran was associated with lower rates of stroke and systemic embolism but similar rates of major hemorrhage as warfarin.

G. Caleb Alexander, MD, of the Johns Hopkins Bloomberg School of Public Health in Baltimore, and colleagues wanted to explore the uptake of dabigatran in clinical practice since its FDA approval. They used the IMS Health National Disease and Therapeutic Index (NDTI) and the IMS Health National Prescription Audit to track national trends between 2007 and 2011. The index is a nationally representative audit of office-based providers based on an ongoing physician survey conducted by IMS Health. The audit is a sample of retail, mail order and mass merchandise pharmacies.

For their study, they analyzed NDTI data to identify office visits where an oral anticoagulant was used, which they termed a treatment visit. They included warfarin, dabigatran but not rivaroxaban (Xarelto, Bayer HealthCare/Janssen Pharmaceuticals). Rivaroxaban received FDA approval in November 2011 for the prevention of stroke in patients with nonvalvular AF.

They also looked at conditions in which oral anticoagulants might be administered, such as AF, venous thromboembolism, coronary artery disease (CAD), heart valve disorders, stroke or transient ischemic attack. Based on audit data, they calculated national estimates of treatment visits, dispensed medications and costs from the first quarter of 2007 through the fourth quarter of 2011.

They found that warfarin treatment visits fell by 500,000 quarterly visits during the study period while dabigatran visits rose by 301,000 quarterly visits. Dabigatran’s share of visits increased from 3.1 percent in the fourth quarter of 2010 to 18.9 percent in the fourth quarter of 2011. Warfarin use for AF remained near 41 percent between the first quarter of 2007 and the fourth quarter of 2011. The proportion of dabigatran visits for AF decreased from 92 percent in the fourth quarter of 2010 to 63 percent in the fourth quarter of 2011, with CAD, hypertensive heart disease and venous thromboembolism the most common off-label uses.

Cardiologists appeared to have fueled the increase in dabigatran use. “Before the availability of dabigatran, the majority of visits reporting oral anticoagulant use were with physicians practicing in internal medicine (30 percent), cardiology (34 percent) and family practice (19 percent), with fewer visits accounted for by physicians affiliated with osteopathy (5 percent), oncology (3 percent) or other specialties (8 percent),” Alexander and colleagues wrote. “By contrast, most dabigatran visits during the five calendar quarters of available data were accounted for by cardiologists (53 percent), with fewer visits associated with internal medicine (28 percent), family practice (10 percent) or other clinical fields (9 percent).”

A previous analysis of the PINNACLE-AF Registry painted a different picture, though. Researchers found that only 12.6 percent of AF patients on anticoagulants were prescribed warfarin alternatives, but that report included both dabigatran and rivaroxaban and captured data from 2011.

Alexander and colleagues added that AF undertreatment remained unchanged during the study period. “Despite the evidence for dabigatran’s improved efficacy in stroke prevention, and its relative ease of use, we did not observe a reduction in atrial fibrillation undertreatment since the introduction of dabigatran,” they wrote. “Rather, approximately one in three atrial fibrillation visits were not associated with any reported antithrombotic therapies.”

Warfarin sales generally held constant, with a slight drop in 2011, while dabigatran sales grew, according to the analysis. Direct expenditures related to dabigatran increased from $16 million in the fourth quarter of 2010 to $166 million in in the fourth quarter of 2010, surpassing warfarin’s $144 million for the 2011 quarter.

The results suggest dabigatran has been "rapidly adopted" into clinical ambulatory practice, the authors concluded. “Significant shifts in oral anticoagulant use are likely as additional therapies become available and evidence accrues regarding their comparative safety and effectiveness relative to conventional therapies,” they added.

The data sources had limited clinical details, did not capture visits to anticoagulation clinics and did not include nonambulatory settings, they pointed out. Given the rapidly evolving landscape in anticoagulation therapy, they anticipated that changes would continue to occur in the use of these therapies.