Warfarin beats out newer anticoagulants for value

When it comes to value, warfarin may be the best option for reducing the risk of stroke and thromboembolism in patients with atrial fibrillation.

William J. Canestaro, MSc, of Brigham and Women’s Hospital in Boston, and colleagues assessed the cost-effectiveness of novel anticoagulants using a model that was built to evaluate four treatment strategies: warfarin managed to an international normalized ratio of 2 to 3; dabigatran (Pradaxa, Boehringer Ingelheim) 150 mg BID; rivaroxaban (Xarelto, Bayer) 20 mg QD; and apixaban (Eliquis, Bristol-Myers Squibb/Pfizer) 5 mg BID. Their cohort was 70-year-old patients with atrial fibrillation with an average CHADS2 of 2 who were eligible to initiate warfarin.

They calculated event rates using data from the anticoagulants’ pivotal trials. Because none of the novel anticoagulants have undergone head-to-head trials, the study indirectly compared the new treatments with each other using warfarin as the common comparator. The results were published online Nov. 12 in Circulation: Cardiovascular Quality and Outcomes.

The analysis set a monthly price of $4 for warfarin; $257 for dabigatran; $242 for rivaroxaban; and $257 for apixaban. Warfarin patients visited a physician four times annually and patients on the novel treatments visited physicians twice annually. All costs were in 2011 dollars.

In their base case analysis, the patient cohort had a quality-adjusted life expectancy of 5.87 years and a total discounted lifetime health cost of $49,638. The novel drugs provided greater quality-adjusted life expectancy than warfarin, but at a cost. Compared with warfarin, the cost per additional quality-adjusted life-year (QALY) gained for dabigatran, rivaroxaban and apixaban were $140,557, $111,465 and $93,062 respectively, making apixaban the optimal strategy.

In sensitivity analyses, increasing the efficacy of rivaroxaban and dabigatran by 8 percent and 18 percent or dropping their costs by $30 and $72, respectively, knocked apixaban from its perch. A probabilistic analysis with a cost-effectiveness threshold of $100,000 per QALY showed apixaban and warfarin to be indistinguishable.

“As a result, our analysis suggests that there is still substantial uncertainty about whether the novel agents are cost-effective,” Canestaro et al wrote. “These comparisons will be clarified further as experience is gained with the real-world use and outcomes of these drugs, as opposed to the randomized trial data on which our analyses are based.”

The study reflected the difficulty of pricing for these comparisons. For instance, pricing information wasn’t available during the study period for apixaban so the researchers ascribed the price for dabigatran to apixaban. The study relied on the lowest available retail prices as of September 2012, and the authors noted that prices for the newer agents rose to $275 after that date.

They also pointed out that study designs for the three pivotal trials differed, although each included a warfarin group as a control. Those differences could affect assumptions on the relative safety and effectiveness over a lifetime horizon.

“[W]hile efficacious and comparatively safe, this agent [apixaban] may not represent good value for the money,” they concluded. “Furthermore, it seems unlikely that rivaroxaban or dabigatran would be cost-effective at their currently assumed prices.”