Apixaban falls short of aspirin as a cost-effective stroke preventive strategy for atrial fibrillation (AF) patients who are unsuitable for warfarin, but only in the short term, according to an analysis in the July issue of Circulation: Cardiovascular Quality and Outcomes. If treatment is extended over years, then apixaban becomes first cost-effective and eventually dominant.

Healthcare decision makers face many challenges when determining the right antithrombotic approaches for preventing stroke in AF patients. While the war horse warfarin is well understood, it is not suitable for some patients if international normalized range levels cannot be achieved, or if the patients refuse to take the drug. Apixaban (Eliquis, Bristol-Myers Squibb and Pfizer), an Xa inhibitor, offered physicians one option for treating these patients based on AVERROES (Apixaban versus Acetylsalicylic Acid to Prevent Strokes) trial results.

The study compared a 5 mg twice daily dose of apixaban with an 81 to 324 mg daily dose of aspirin and found that apixaban showed superior efficacy over aspirin, reducing the risk of stroke by 63 percent.

Based on those positive findings, Soyon Lee, PharmD, of the University of Connecticut School of Pharmacy in Storrs, and colleagues wanted to determine if apixaban also was a cost-effective alternative to aspirin. They used data from AVERROES to estimate the quality-adjusted life-years (QALYs), costs and cost-effectiveness of apixaban compared with aspirin in AF patients who were deemed unsuitable for warfarin.

The base case assumed a 70-year-old patient cohort which a CHADS₂ score of 2 and a lower risk of bleeding. The researchers constructed a Markov cohort transition state model to determine incremental cost-effectiveness ratios (ICERs) and performed sensitivity analyses for the trial length (short term) and life-time models.

They calculated base-case total costs per patient of $3,454 for apixaban and $1,805 for aspirin in the trial length and $44,232 for apixaban and $50,066 for aspirin over 10 years. In the trial-length model, the QALYs were 0.96 for both treatments and in the 10-year model the QALYs were 6.87 for apixaban and 6.51 for aspirin. Based on those figures, apixaban was more costly and no more effective (inferior) in the trial-length model but less costly and more effective (dominant) in the 10-year model.

Lee and colleagues wrote that the ICER for apixaban became more favorable as the time period was extended, falling below the $50,000 per QALY measure of becoming cost-effective between 36 and 42 months and dominant by the sixth year. At 10 years, apixaban provided an additional 0.36 QALYs with a savings of $5,834 compared with aspirin.

“Apixaban’s superior efficacy in preventing ischemic stroke, without increasing major bleeding risk compared with aspirin, probably explains our finding that apixaban is economically dominant in the 10-year model despite prices significantly higher than aspirin,” Lee and colleagues wrote. “Upon one-way sensitivity analysis, a reduction in the baseline stroke rate/CHADS₂ score had a significant effect on the cost-effectiveness of apixaban in both model durations.”

The researchers cautioned that their results were based on AVERROES data, which had a mean follow-up of one year because the trial was stopped early. To conduct their analysis, they assumed benefits and harms associated with apixaban were constant over time.

“It is possible that rates of adverse events for apixaban or aspirin may vary with a longer follow-up period,” they wrote. “Thus, such assumptions would clearly decrease the internal validity of our analysis.”

They also noted that their study compared apixaban with aspirin but did not address the entry of newer alternative therapies such as dabigatran (Pradaxa, Boehringer Ingelheim) and rivaroxaban (Xarelto, Bayer HealthCare/Janssen Pharmaceuticals).

Apixaban has yet to be approved for the prevention of stroke in patients with AF in any country. It received a priority review designation from the FDA in November 2011, and in February the FDA extended the action date by three months, to June 28.  

“Based on apixa­ban’s superior stroke reducing efficacy, similar rate of major bleeding and economic dominance compared with aspirin, it appears to be a highly attractive alternative (if approved) in patients with AF who deemed unsuitable for warfarin,” they concluded.