Apixaban Less Costly Than Aspirin for Stroke Prevention in A-Fib at 10 Years

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In patients with atrial fibrillation (A-fib) considered unsuitable for warfarin, the novel anticoagulant apixaban is more cost-effective than aspirin for stroke prevention over a 10-year period, a difference that is not apparent at 1 year, according to a cost analysis published online June 26, 2012, ahead of print in Circulation: Cardiovascular Quality and Outcomes.

Using data from the randomized AVERROES trial, a team led by Craig I. Coleman, MD, of the University of Connecticut School of Pharmacy (Storrs, CT), constructed a Markov model to estimate costs in 2011 US dollars and calculate quality-adjusted life years (QALYs) from a Medicare perspective for aspirin and the oral factor Xa inhibitor apixaban (Eliquis; Bristol-Myers Squibb/Pfizer). Numbers were based on a hypothetical cohort of 70-year-old patients with CHADS₂ scores of 2 and low bleeding risk. Two
follow-up durations were considered: the 1-year trial length of AVERROES and 10-year follow-up.

AVERROES, originally published in the New England Journal of Medicine in March 2011, randomized patients to apixaban (5 mg twice daily) or aspirin (81-324 mg daily). All subjects had been deemed by investigators to be unsuitable for warfarin, whether because of patient refusal, inability to measure international normalized ratio at requested intervals, or some other reason. Apixaban showed superior efficacy to aspirin, reducing the annual ischemic stroke risk by 63% (P < 0.001), without significantly increasing major bleeding events.

Apixaban Eventually Comes Out Ahead

In the current analysis, Dr. Coleman and colleagues found that at 1 year, the total costs per patient were significantly higher with apixaban vs. aspirin. Moreover, both groups obtained similar benefit from therapy. But by 10 years, apixaban was the dominant treatment in terms of both cost and efficacy (table 1).

Table 1. Outcomes According to Anticoagulant Therapy

The incremental cost-effectiveness ratio for apixaban became gradually more favorable from 1 to 10 years, with the drug falling below a willingness-to-pay threshold of $50,000 between 3 and 3.5 years. Apixaban beat aspirin for both cost and efficacy at around 6 years.

Additional calculations found that apixaban would only be a cost-effective alternative ($50,000 threshold) to aspirin in 11% of 10,000 hypothetical cases using the 1-year model. But using the 10-year model, apixaban would be cost-effective in 96.7% of cases and dominant in 87.5%.

Over 1 decade of therapy, apixaban was more affordable and protective than aspirin for patients at moderate to high risk of stroke (CHADS₂ score ≥ 2). Patients at low stroke risk, meanwhile, stood to gain no additional efficacy from apixaban vs. aspirin, though the newer drug remained cost-effective.

Putting the Gains into Perspective

Dr. Coleman told TCTMD in an e-mail communication that the results are “not entirely unexpected” given apixaban’s strong showing in AVERROES. “Even though apixaban costs more than aspirin, in the long run (over 10 years or more) it actually saves the health care system money by reducing ischemic strokes and the morbidity and mortality associated with them,” he explained.

Commenting on the actual difference in QALYs, Dr. Coleman acknowledged that “[o]n average a patient will live 4 months longer (some more, some less)” using the 10-year data.

“More importantly, however, (again on average) it will cost patients less money to do so,” he continued. “In cost-effectiveness analyses, we should always try to look at the costs and efficacy of the agents jointly.”

Dr. Coleman added that “it is also important to point out that this is not compared to placebo, but rather aspirin, so we would not expect as large of an effect. I think clinicians will be most convinced by the clinical trial data for apixaban, but payors will be looking at studies like ours to determine cost-effectiveness and to make coverage decisions.”

David J. Cohen, MD, MSc, of Saint Luke’s Mid America Heart and Vascular Institute (Kansas City, MO), also stressed that QALY data should not be viewed on a per patient basis.

“Although it is possible that a gain in QALYs of 0.36 years could reflect an extension of life by about 4 months for each patient, this is not what actually happens—either in the model or in real life,” he explained to TCTMD in an e-mail communication. “What actually drives this benefit is a much larger gain in quality-adjusted life expectancy of several years among the modest proportion of patients who derive measurable benefit (such as stroke prevention) and no gain whatsoever in a larger proportion of patients who would never have had an event on either aspirin or apixaban.”

According to Dr. Cohen, many previous studies have found oral anticoagulation to be an “economically attractive strategy” in A-fib patients with moderate to high stroke risk. But this analysis is the first one to directly examine apixaban, he said, noting that while models are inherently uncertain, it appears that in this case the study methodology is solid. That being said, “there is substantial uncertainty as to the duration of benefit of apixaban in this setting, because the AVERROES clinical trial only followed patients for approximately 1 year,” Dr. Cohen observed.

Uncertainty in the System

As to whether the changing US health care system matters when looking at such a long-term horizon, it is hard to say, Dr. Coleman noted. “I think a lot remains to be seen about [how] the ‘overhaul’ will be carried out,” he commented. “The best I can say for now is that as payors (government or private) find themselves insuring more Americans, they will need to keep a close eye on whether new, more expensive therapies are cost-effective.  These studies can help them make these determinations.”

Dr. Cohen agreed, observing that. “as physicians enter into more ‘risk sharing’ arrangements (such as accountable care organizations), it is likely that they will need to consider trade-offs between cost and benefits as one of the factors in guiding treatment decisions and policies.”

In May 2011, apixaban received CE Mark approval in Europe for the prevention of venous thromboembolism in patients who have undergone elective hip or knee replacement surgery. The US Food and Drug Administration was expected to deliver its verdict regarding apixaban for stroke prevention in A-fib patients on June 25, 2012, but delayed the decision for another 3 months. The agency has requested additional information from the pivotal ARISTOTLE trial, published in NEJM in September 2011.

 

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Source:
Lee S, Anglade MW, Meng J, et al. Cost-effectiveness of apixaban compared with aspirin for stroke prevention in atrial fibrillation among patients unsuitable for warfarin. Circ Cardiovasc Qual Outcomes. 2012;Epub ahead of print.

 

 

Related Stories:

• Apixaban Bests Warfarin in Stroke Prevention for Atrial Fib
• Apixaban Prevents Stroke in A-fib Patients Irrespective of Previous Stroke/TIA
• Rivaroxaban May be Cost-Effective for A-fib Patients

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