Apixaban Cost-Effective Compared with Warfarin or Aspirin

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Apixaban is a cost-effective alternative to warfarin in warfarin-suitable candidates and also compares well with aspirin in patients who cannot take the vitamin K antagonist. The findings, derived from randomized trial data, were published online February 16, 2014, ahead of print in the European Heart Journal.

Using data from the ARISTOTLE and AVERROES trials, researchers led by Paul Dorian, MD, of St. Michael’s Hospital Toronto (Toronto, Canada), constructed a model to estimate costs from the United Kingdom payer perspective for aspirin, warfarin, and the oral factor Xa inhibitor apixaban (Eliquis; Bristol-Myers Squibb/Pfizer, New York, NY).

Clinical events in the model included:

  • Ischemic stroke
  • Hemorrhagic stroke
  • Intracranial hemorrhage
  • Other major bleed
  • Clinically relevant non-major bleed
  • MI
  • Cardiovascular hospitalization
  • Treatment discontinuation

Mortality and event related utility rates were derived from published trials.

Apixaban Comes Out Ahead

Among a hypothetical cohort of 1,000 warfarin candidates over a lifetime, use of apixaban resulted in fewer cases of stroke/systemic embolism, major bleeding, and cardiovascular-related death. In a population of 1,000 patients unsuitable for warfarin, use of apixaban compared with aspirin was predicted to reduce stroke/systemic embolism and cardiovascular-related death but also to increase major bleeding and cardiovascular hospitalization (table 1)

Table 1. Change in Events in 1,000 Patients Over Lifetime


Apixaban vs Warfarin

Apixaban vs Aspirin

Stroke/Systemic Embolism



Major Bleeding



CV Death



CV Hospitalization


The number needed to treat with apixaban to avoid 1 stroke over a lifetime was 56 in the warfarin-suitable group and 18 in the non-warfarin group.

Apixaban use compared with either warfarin or aspirin resulted in an incremental cost ratio (ICER) that fell below the accepted threshold of £20,000, or approximately $33,000 US dollars (table 2).

Table 2. Cost-Effectiveness of Apixaban


QALY Gained

Incremental Cost

ICER per QALY Gained









Abbreviations: QALY, quality adjusted life year; ICER, incremental cost ratio.

Sensitivity analyses demonstrated that the model’s findings were robust, including a wide range of inputs. At a willingness to pay of £20,000 per QALY gained, apixaban was cost-effective and offered maximum net benefit over warfarin 93% of the time and aspirin 99% of the time.

According to Dr. Dorian and colleagues, the higher treatment cost for apixaban stemmed from 2 factors: the price of the drug itself and the additional time patients spent taking it (due to longer expected lifetime and lower discontinuation rates).

“[T]he choice of an optimal anticoagulant in [A-fib] patients should involve careful consideration of stroke prevention efficacy, bleeding risk, tolerability profile, and resource burden associated with therapeutic management,” the researchers advise. “Our analysis demonstrates that apixaban, when compared with the current standard of care provides a cost-effective alternative for prevention of thromboembolic events.”

Study Appears Methodologically Sound

In an e-mail, David J. Cohen, MD, MSc, of Saint Luke’s Mid America Heart Institute (Kansas City, MO), told TCTMD that the “study adds to the growing body of knowledge evaluating the cost-effectiveness of novel anticoagulants compared with warfarin for patients with non-valvular atrial fibrillation.” Two unique qualities of the current study stand out, he said: the evaluation of apixaban vs aspirin in patients who are not warfarin candidates and the careful modeling of drug discontinuation and switching after bleeding events.

Dr. Cohen said that, although all modeling studies involve compromise between comprehensiveness and feasibility, “it appears that the authors have done a reasonable job in considering the important outcomes that drive survival and health status” for A-fib patients. In particular, the investigators’ access to clinical trial data enabled them “to tease out nuances in various outcome probabilities to inform their model that were not available in the published data,” he added.

“Very importantly, the authors . . . conducted extensive sensitivity analyses to identify those factors that ‘drive’ the cost-effectiveness results and also a probabilistic sensitivity analysis to understand the effect of uncertainty,” Dr. Cohen commented. “The fact that the results are robust over a wide range of alternative assumptions is very reassuring.”

While it is difficult to apply the current findings to the US setting, Dr. Cohen noted, “most cost-effectiveness studies of novel anticoagulants in the United States have found similar results—that the novel anticoagulants increase overall health care costs (mainly due to drug acquisition costs), but by preventing strokes and in some cases bleeding, they improve life expectancy and quality-adjusted life expectancy for the target population at a reasonable cost.”


Dorian P, Kongnakorn T, Phatak H, et al. Cost-effectiveness of apixaban vs current standard of care for stroke prevention in patients with atrial fibrillation. Eur Heart J. 2014;Epub ahead of print.



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  • The research, including the development of the model, its design, construction, and identification of model inputs was supported by Bristol-Myers Squibb and Pfizer. The open access publication charges for the article were funded by a grant from Bristol-Myers Squibb and Pfizer.
  • Dr. Dorian reports receiving honoraria and research support from Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, and Pfizer.
  • Dr. Cohen reports receiving researcher grants to his institution from and serving as a consultant to Daiichi-Sankyo.

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