Economic Analysis of Apixaban Therapy for Patients With Atrial Fibrillation From a US Perspective: Results From the ARISTOTLE Randomized Clinical Trial

Abstract

Importance: The Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial reported that apixaban therapy was superior to warfarin therapy in preventing stroke and all-cause death while causing significantly fewer major bleeds. To establish the value proposition of substituting apixiban therapy for warfarin therapy in patients with atrial fibrillation, we performed a cost-effectiveness analysis using patient-level data from the ARISTOTLE trial.

Objective: To assess the cost and cost-effectiveness of apixaban therapy compared with warfarin therapy in patients with atrial fibrillation from the perspective of the US health care system.

Design, setting, and participants: This economic analysis uses patient-level resource use and clinical data collected in the ARISTOTLE trial, a multinational randomized clinical trial that observed 18 201 patients (3417 US patients) for a median of 1.8 years between 2006 and 2011.

Interventions: Apixaban therapy vs warfarin therapy.

Main outcomes and measures: Within-trial resource use and cost were compared between treatments, using externally derived US cost weights. Life expectancies for US patients were estimated according to their baseline risk and treatment using time-based and age-based survival models developed using the overall ARISTOTLE population. Quality-of-life adjustment factors were obtained from external sources. Cost-effectiveness (incremental cost per quality-adjusted life-year gained) was evaluated from a US perspective, and extensive sensitivity analyses were performed.

Results: Of the 3417 US patients enrolled in ARISTOTLE, the mean (SD) age was 71 (10) years; 2329 (68.2%) were male and 3264 (95.5%) were white. After 2 years of anticoagulation therapy, health care costs (excluding the study drug) of patients treated with apixaban therapy and warfarin therapy were not statistically different (difference, -$60; 95% CI, -$2728 to $2608). Life expectancy, modeled from ARISTOTLE outcomes, was significantly longer with apixaban therapy vs warfarin therapy (7.94 vs 7.54 quality-adjusted life years). The incremental cost, including cost of anticoagulant and monitoring, of achieving these benefits was within accepted US norms ($53 925 per quality-adjusted life year, with 98% likelihood of meeting a $100 000 willingness-to-pay threshold). Results were generally consistent when model assumptions were varied, with lifetime cost-effectiveness most affected by the price of apixaban and the time horizon.

Conclusions and relevance: Apixaban therapy for ARISTOTLE-eligible patients with atrial fibrillation provides clinical benefits at an incremental cost that represents reasonable value for money judged using US benchmarks for cost-effectiveness.

Trial registration: clinicaltrials.gov Identifier: NCT00412984.

Conflict of interest statement

Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Cowper has received research support from Bristol-Myers Squibb, Pfizer, Eli Lilly, Tenax Therapeutics, Gilead Sciences, AGA Medical Corporation, AstraZeneca, and General Electric. Dr Lopes has received research grants from Bristol-Myers Squibb, Pfizer, GlaxoSmithKline and consulting fees from Bayer Corporation, Boehringer Ingelheim, Bristol-Myers Squibb, Merck, Pfizer, and Portola. Dr Anstrom has received research grants from Bristol-Myers Squibb and Pfizer. Dr Ansell served as an advisor or consultant for Boehringer Ingelheim Pharmaceuticals, Bristol-Myers Squibb, Daiichi Sankyo, Janssen Pharmaceuticals, and Pfizer. Dr Dorian has received grants for clinical research from as well as served as a consultant and a speaker for Bayer HealthCare Pharmaceuticals, Boehringer Ingelheim Pharmaceuticals, Bristol-Myers Squibb, and Pfizer. Dr Husted has received research grants from Boehringer Ingelheim and Bristol-Myers Squibb, honoraria from AstraZeneca, Bayer, Bristol-Myers Squibb, Boehringer Ingelheim, and Pfizer, and consultant board fees from AstraZeneca, Bayer, Boehringer Ingelheim, and Bristol-Myers Squibb. Dr McMurray has received support from Novartis, Cardiorentis, Amgen, Oxford University/Bayer, GlaxoSmithKline, Theracos, Abbvie, DalCor, Pfizer, Merck, AstraZeneca, Bristol-Myers Squibb, and Kidney Research UK/Kings College Hospital/Vifor-Fresenius. Dr Steg has received research grants from Merck, Sanofi, and Servier and consulting fees from Amarin, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, CSL-Behring, Daiichi-Sankyo, GlaxoSmithKline, Janssen, Lilly, Merck, Novartis, Pfizer, Regeneron, Sanofi, Servier, and The Medicines Company. Dr Alexander has received institutional research grants from Boehringer Ingelheim, Bristol-Myers Squibb, CSL Behring, Pfizer, Tenax Therapeutics, Regado Biosciences, Sanofi, and Vivus Pharmaceuticals and consulting fees from Bristol-Myers Squibb, Portola, and Somahlution. Dr Wallentin has received research grants from AstraZeneca, Merck, Boehringer Ingelheim, Bristol-Myers Squibb, and Pfizer, GlaxoSmithKline, and Roche and consulting fees or honoraria from Boehringer Ingelheim, AstraZeneca, GlaxoSmithKline, Abbott, and Bristol-Myers Squibb, and Pfizer. Dr Granger has received research grants from Boehringer Ingelheim, Bristol-Myers Squibb, GlaxoSmithKline, Medtronic Foundation, Merck & Co, Pfizer, Sanofi Aventis, Takeda, The Medicines Company, AstraZeneca, Daiichi Sankyo, Janssen Pharmaceuticals, Bayer, and Armetheon and consulting fees from Boehringer Ingelheim, Bristol-Myers Squibb, GlaxoSmithKline, Hoffmann-LaRoche, Eli Lilly, Pfizer, Sanofi Aventis, Takeda, The Medicines Company, AstraZeneca, Daiichi Sankyo, Ross Medical Corporation, Janssen Pharmaceuticals, Salix Pharmaceuticals, Gilead, and Medtronic Inc. Dr Mark has consulted for Medtronic, CardioDx, and St Jude Medical and received research grants from Eli Lilly, Medtronic, Bristol-Myers Squibb, Pfizer, AstraZeneca, Merck & Company, Oxygen Therapeutics, and Gilead. No other disclosures were reported.

Figures

Figure 1.. Distribution of Lifetime Incremental Cost and Effectiveness

Estimates of incremental cost and quality-adjusted life-years (QALYs) for the base case (1 black circle for each of 1000 bootstrap samples). The solid red circle indicates the point estimate. Difference indicates apixaban group minus warfarin group.

Figure 2.. Cost-effectiveness Acceptability Curves: Varying Assumptions Regarding Cost, Effectiveness, and Patient Risk

A, Effect of varying assumptions regarding the cost of health care services and apixaban therapy on the probability of cost-effectiveness at a range of willingness-to-pay thresholds. B, Effect on cost-effectiveness of removing quality-of-life adjustment, restricting the time horizon, and basing analysis on the total study cohort. C, Cost-effectiveness of apixaban therapy for different levels of thromboembolic risk. QALY indicates quality-adjusted life-year.