Novel Anticoagulants Cost-Effective vs. Warfarin in A-fib Patients

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Each of the 3 recently approved anticoagulants that have entered the US market—apixaban, dabigatran, and rivaroxaban—are more cost-effective than warfarin for stroke prevention in patients with nonvalvular atrial fibrillation (A-fib), according to a study published online April 2, 2013, ahead of print in Stroke.

Daniel C. Malone, PhD, and colleagues at the University of Arizona (Tucson, AZ), created a Markov decision-analysis model using data from the pivotal ARISTOTLE, RE-LY, and ROCKET-AF trials to evaluate cost and quality-adjusted life-years (QALYs) for apixaban 5 mg, dabigatran 150 mg, and rivaroxaban 20 mg, respectively, compared with warfarin. The hypothetical population comprised 70-year-old patients with nonvalvular A-fib and CHADS2 scores of 1 or higher, renal creatinine clearance of 50 mL/min or more, and no contraindications to anticoagulation.

Apixaban Takes the Lead

Warfarin had the lowest estimated cost but also produced fewer QALYs, while apixaban offered the best value, despite being the most expensive. The incremental cost-effectiveness ratio for apixaban vs. warfarin was $15,026 per QALY. Using a willingness-to-pay threshold of $50,000 per QALY gained, additional analyses estimated that apixaban is likely to be cost effective nearly half the time and warfarin none of the time (table 1).

Table 1. Cost-Effectiveness of Various Anticoagulants

 

Apixaban

Dabigatran

Rivaroxaban

Warfarin

Total Cost

$85,326

$82,719

$78,738

$77,813

QALYs Gained

8.47

8.41

8.26

7.97

Odds of Being Cost-Effective

45.1%

40%

14.9%

0


Apixaban stands out in the current study as the “preferred anticoagulant” among the new options, the investigators conclude.

Researchers calculated 1-time costs for adverse events including ischemic stroke, intracranial hemorrhage, MI, GI bleeding, and dyspepsia using 2009 US dollars, factoring in long-term costs related to use of acute services within 12 months after ischemic stroke or intracranial hemorrhage using 2012 US dollars. Prescription drug costs were based on wholesale pricing.

QALY Difference ‘Substantial’

In a telephone interview, Michael D. Ezekowitz, MD, PhD, of Thomas Jefferson Medical College (Philadelphia, PA), said, “One of the major questions being asked about the new anticoagulants is the cost effectiveness of these agents. There are 2 factors. One is the actual cost of the medication, and obviously that represents an increase, because warfarin, which they’re designed to replace, is very cheap—cents on the dollar. But then there is the added benefit of these drugs, particularly dabigatran and apixaban.”

The overall balance reached between these 2 factors “is reflected in this paper,” he commented to TCTMD. “The differences [in QALYs] seem quite substantial, especially if you take the differences over a patient’s lifetime and not just on an annual basis.”

In a telephone interview with TCTMD, study coauthor Amanda R. Harrington, MS, also of the University of Arizona, likewise used the word “substantial” to describe the observed gains in QALYs of the newer drugs over warfarin.

Findings ‘Tough to Interpret’

As for pitting the various agents against one another, however, Dr. Ezekowitz was circumspect. “[W]e’re scratching the surface of how they differ, one from another,” he said. “They have important similarities, because these drugs were specifically synthesized to achieve a certain goal [of being noninferior to warfarin]. . . . They’re all better than warfarin. I think we can safely say that. How they stack up against one another on a cost-effective basis is more difficult to figure out.”

David J. Cohen, MD, MSc, of Saint Luke’s Mid America Heart Institute (Kansas City, MO), described the study as “tough to interpret.”

“I think the most solid conclusion one can draw from this paper is that all 3 of the novel agents are reasonably cost-effective compared with warfarin [since the analyses are based on actual trials],” he told TCTMD in a telephone interview.

But “it’s very dicey to draw strong conclusions” when trying to compare among the newer drugs, Dr. Cohen stressed, adding that the researchers did the best they could with available data. He also highlighted the fact that, because apixaban had only recently been approved by the US Food and Drug Administration at the time of analysis, the researchers used the price of the drug in the United Kingdom (approximately $5.20 per day) instead of its actual price on the US market.

“We have the need for more direct comparisons. I don’t know if they will ever be done on the different agents. Given the size of the population, there certainly would be strong reason on the part of the public to do those trials,” Dr. Cohen concluded, predicting that eventually registries, though also limited, will provide the needed information.

In the paper, Dr. Malone and colleagues agree that the current findings should be interpreted with caution. “A notable limitation in this study is the need to [base the model on] values from a variety of different sources,” they say, pointing to differences in trial design, outcome definitions, and patient populations. Among other caveats, they specify that clinical practice may also differ from trials in terms of dosing, monitoring, comorbidities, and lack of compliance.

While trials give the most direct evidence, modeling can indirectly incorporate information and help put it into a framework like QALYs that is more universal, Dr. Malone explained. “Yes, you do have to be careful drawing definitive conclusions from analysis between these agents, but I think that the differences among the newer oral anticoagulants are relatively small as compared to [their overall advantage over] warfarin,” he told TCTMD in a telephone interview.

Ultimately, “[r]eal-world data for these therapies need to be collected,” since randomized trials represent the best-case scenario, Ms. Harrington commented.

 


Source:
Harrington AR, Armstrong EP, Nolan EP Jr, et al. Cost-effectivenes of apixaban, dabigatran, rivaroxaban, and warfarin for stroke prevention in atrial fibrillation. Stroke 2013;Epub ahead of print.

 

 

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Disclosures
  • Dr. Malone reports no relevant conflicts of interest.
  • Dr. Ezekowitz reports serving as co-principal investigator for the RE-LY and X-ERT trials; receiving consulting fees, lecture fees, and grant support from Aryx Therapeutics and Boehringer-Ingelheim; consulting fees from Sanofi-Aventis; and lecture fees and grant support from Portola Pharmaceuticals.
  • Dr. Cohen reports receiving consulting fees from Bristol-Myers Squibb and Janssen.

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