Novel Anticoagulants Under the Fiscal Microscope

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201300043_Malone_DSC4640.jpg - DanielMalone
Daniel Malone, RPh, PhD, a pharmacy professor at the University of Arizona in Tucson, acknowledges that novel anticoagulants may be expensive but the prices aren't exorbitant, either. Source: The University of Arizona College of Pharmacy.
Source: The University of Arizona College of Pharmacy

Novel oral anticoagulants (NOACs) may beat warfarin for cost-effectiveness, but does that mean they offer a genuinely good value? Physicians and payers might answer that question differently.

Heads or tails: warfarin or NOACs for preventing stroke in some atrial fibrillation patients? Talk with researchers who’ve asked that question, and it becomes clear that it is a coin toss. The decision comes down to the preference of the prescribing physician, shaped by his or her experience and views on efficacy and ease of use.

The picture doesn’t get much clearer when you add cost-effectiveness into the mix, but that’s where the conversation has been moving as U.S. healthcare continues to stress price considerations in clinical decision-making—and as the NOAC market, driven by aggressive direct-to-consumer marketing, grows by leaps and bounds.

Three FDA-approved drugs in the category have been duking it out with warfarin and each other: Bayer/Johnson & Johnson’s rivaroxaban (Xarelto), Boehringer Ingelheim’s dabigatran (Pradaxa), and, from Bristol-Myers Squibb and Pfizer, apixiban (Eliquis). In early 2015, Daiichi Sankyo’s edoxaban (Savaysa), also won FDA clearance, making it the fourth approved option. It may be closely followed by Portola/Merck’s betrixaban.

EvaluatePharma forecasts the NOAC market will expand by 11.5 percent annually until it hits $15.3 billion in sales by 2018. If that holds, there soon may be four or five blockbusters in one very lucrative drug category.

Sixty-year-old warfarin enjoys the benefits of familiarity, along with its reversibility when bleeding occurs or is likely, as in planned surgery. EvaluatePharma shows warfarin still captures more than 30 percent of the U.S. market, although rivaroxaban has displaced it as category leader for first-time anticoagulant prescriptions. But dosing remains difficult, food interactions are common and frequent monitoring for prothrombin time and international normalized ratio (INR) is required.

By contrast, the NOACs need little to no monitoring and carry less risk of causing brain hemorrhage and stomach bleeds. Clinically their biggest drawback is that they have no antidote—yet. At least two reversal agents have shown promise in trials.

As for price, the NOACs are steep while warfarin (Bristol-Myers Squibb’s Coumadin, generics from numerous factories) is cheap. This has some questioning the wisdom of rushing to replace the old with the new on a broad scale in a time of cost-containment, especially if the NOACs are not vastly safer and more efficacious than the established treatment.

Expensive but (sometimes) worth it

Harvard Medical School’s Niteesh K. Choudhry, MD, PhD, a hospitalist at Brigham and Women’s Hospital in Boston whose research concentrates on evaluating novel strategies for improving care quality while reducing costs, says the NOACs offer a game-changing therapy for many patients. However, they may not represent good value for the money (Circ Cardiovasc Qual Outcomes online Nov. 13, 2013).  

“Apixaban fell just below the $100,000 per quality-adjusted life year [QALY] threshold,” Choudhry explains. “That’s not bad in and of itself; it suggests that the drug may represent good value. But there are so many unknowns about how these drugs work in the real world and, when you subject an analysis of cost to sensitivity analyses and you re-run them, it’s not so clear. And, in fact, warfarin came out to be the winner in more simulations than apixaban. Hence our conclusion.”

He notes that, throughout healthcare, $50,000 remains the benchmark threshold for QALY more than 20 years after it was established.

In 2014 Choudhry and colleagues looked at trends in utilization of NOACs and the resulting economic outlays (Am J Med. 2014;127[11]:1075-1082). The study zeroed in on atrial fibrillation patients initiating an oral anticoagulant, and the data showed that rapid adoption of NOACs into clinical practice has high-cost consequences.

“In and of itself, use of these drugs may represent good clinical value,” says Choudhry. “In fact, as a practicing doctor, I have a lot of enthusiasm for these medications. Clinically, they represent a vast improvement over warfarin in many regards. But seeing the value is really sort of a societal judgment. As a whole, given limited budgets, which we are all unfortunately faced with, do these really represent overall good value for society? The answer is not exactly clear.”

Choudhry adds that analyses of cost-effectiveness tend to