NOACs have several advantages over warfarin, including no routine monitoring requirement, predictable pharmacodynamics, and fewer food and drug interactions. Their cost, however, remains an important concern for patients and care providers. Newer anticoagulants should reduce clinician and patient time commitments associated with routine monitoring of INR required with warfarin.1 Fewer drug–drug and drug–food interactions may result in less frequent suboptimal anticoagulation and will virtually eliminate the need for dose adjustments. All anticoagulants can cause bleeding. Yet, NOACs have different pharmacodynamic properties that may reduce bleeding risk in susceptible patients.
Anticoagulant-related bleeding complications are expensive, particularly major bleeding events that require hospitalization. Intracranial hemorrhage (ICH) and major gastrointestinal (GI) bleeding increase mean 12-month healthcare costs by $17,774 and $16,457, respectively.2 Overall, clinical trials have shown that ICH occurs much less frequently with dabigatran, rivaroxaban, apixaban, and edoxaban compared with warfarin. In contrast, dabigatran, rivaroxaban, and edoxaban have produced more GI bleeding when compared to warfarin, whereas apixaban has shown similar rates of GI bleeding events.3-6 Dabigatran and rivaroxaban produced similar incidences of major bleeding episodes compared to warfarin, while apixaban and edoxaban produced a lower incidence.
Several cost-effectiveness analyses have evaluated NOAC use in stroke prophylaxis. Data from the RE-LY study showed that patients’ quality-adjusted life expectancy was increased from 10.28 quality-adjusted life-years (QALYs) with warfarin to 10.84 QALYS with high-dose dabigatran.7 The incremental cost-effectiveness ratio compared with warfarin was $45,372 per QALY for high-dose dabigatran, which is cost-effective when compared to a $50,000 willingness-to-pay threshold. The cost-effectiveness of high-dose dabigatran increased with higher risk for stroke and ICH. In a hypothetical cohort study of 70-year-old AF patients evaluating dabigatran 110 or 150 mg twice daily, warfarin, dual therapy with aspirin and clopidogrel, aspirin alone, or no antithrombotic, dabigatran 150 mg twice daily had the greatest quality-adjusted survival at 8.65 QALYs, compared with 8.40 QALYs for aspirin.7 Cost-effectiveness depended highly on stroke, risk of hemorrhage, cost of dabigatran, and time in therapeutic range (TTR) for warfarin. For patients with a CHADS2 score of ≥3 (high risk of stroke), dabigatran 150 mg twice daily was cost-effective unless INR control was excellent (TTR >72.6%). In the RE-LY, ROCKET AF, ARISTOTLE, and ENGAGE trials the median TTRs were 64%, 55%, 64%, 68.4%, respectively, demonstrating that it is difficult to manage in many patients.
Rivaroxaban cost-effectiveness was compared to adjusted-dose warfarin for stroke prevention using a model with a Medicare perspective and a lifetime time horizon.8 Outcome measurements included costs in 2011 United States dollars, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs). Patients with AF treated with rivaroxaban lived an average of 10.03 QALYs at a lifetime treatment cost of $94,456. Those receiving warfarin lived an average of 9.81 QALYs and incurred costs of $88,544. The ICER for rivaroxaban was $27,498 per QALY. This model showed that rivaroxaban therapy may be a cost-effective alternative to adjusted-dose warfarin for stroke prevention in AF.
Researchers followed a group of non-valvular AF patients longitudinally for thrombosis and bleeding endpoints.9 Despite their “real world” AF population comprised primarily of low risk patients (78.5% had CHADS2 scores of ≤2), the stroke rate was high, 5.3 events per 100 patient years overall, and 3.2 and 5.7 events per 100 patient years in those with CHADS2 scores of 1 and 2, respectively. Major bleeding was also alarmingly high at 10 events per 100 patient years. The risk reductions from the ARISTOTLE trial, apixaban compared against warfarin for stroke prophylaxis, was applied to the “real world” population to determine event rates had apixaban been used instead of warfarin. The application of the apixaban risk reduction to the ‘real world’ population avoided 1.1 stroke events per 100 patient years and avoided 2.1 major bleeding events per 100 patient years. The authors estimated that apixaban use would generate an incremental medical cost avoidance for stroke of $493 during a patient year and $752 for major bleeding events during a patient year. The combined cost avoidance for stroke and major bleeding was $1,245 during a patient year. Overall, the medical cost avoidance increased as patient stroke risk increased.
Patients have major concerns regarding out-of-pocket expenses associated with drug therapy. The NOACs typically fall into a higher insurance tier and have higher co-payments than warfarin. Many patients with AF are elderly, on fixed incomes, and have other medication needs, hence the importance of recognition of a patient’s financial situation. While warfarin has a low acquisition cost, other less obvious expenses such as transportation to anticoagulation clinics or laboratories for INR monitoring and dose adjustments require consideration. The estimated associated annual costs range from $130 for patients attending clinics monthly to $560 for patients attending clinics weekly.10 Warfarin therapy also consumes patient time. Anticoagulation clinic visits, phone communication with providers, and pharmacy trips require an estimated average of 91.7 hours annually for warfarin therapy. Therefore the anticoagulant choice in stroke prevention requires reflection by the patient and provider and consideration of time and financial constraints.
AF-related stroke contributes considerably to healthcare expenditures. Although warfarin has been the standard of preventive care for decades, the NOACs now furnish options.Early economic studies support the cost effectiveness of NOACs, since they reduce stroke and systemic embolism as well as bleeding events, including ICH. As the cost of NOACs decreases over time, cost-effectiveness considerations may more heavily favor the NOACs over warfarin in the future.
1. Ansell J, Hirsh J, Hylek E, Jacobson A, Crowther M, Palareti G. Pharmacology and management of the vitamin K antagonists: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition).Chest.2008;133(6 Suppl):160S-198S.
2. Ghate SR, Biskupiak J, Ye X, Kwong WJ, Brixner DI. All-cause and bleeding-related health care costs in warfarin-treated patients with atrial fibrillation.J Manag Care Pharm.2011;17(9):672-684.
3. Patel MR, Mahaffey KW, Garg J, et al. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation.N Engl J Med.2011;365(10):883-891.
4. Granger CB, Alexander JH, McMurray JJ, et al. Apixaban versus warfarin in patients with atrial fibrillation.N Engl J Med.2011;365(11):981-992.
5. Giugliano RP, Ruff CT, Braunwald E, et al. Edoxaban versus warfarin in patients with atrial fibrillation.N Engl J Med.2013;369(22):2093-2104.
6. Freeman JV, Zhu RP, Owens DK, et al. Cost-effectiveness of dabigatran compared with warfarin for stroke prevention in atrial fibrillation.Ann Intern Med.2011;154(1):1-11.
7. Shah SV, Gage BF. Cost-effectiveness of dabigatran for stroke prophylaxis in atrial fibrillation.Circulation.2011;123(22):2562-2570.
8. Amin A, Stokes M, Wu N, et al. Estimated medical cost reductions associated with apixaban in real-world patients with non-valvular atrial fibrillation.J Med Econ.2013;16(10):1193-1202.
9. Hwang JM, Clemente J, Sharma KP, Taylor TN, Garwood CL. Transportation cost of anticoagulation clinic visits in an urban setting.J Manag Care Pharm.2011;17(8):635-640.
10. Jonas DE, Bryant Shilliday B, Laundon WR, Pignone M. Patient time requirements for anticoagulation therapy with warfarin.Med Decis Making.2010;30(2):206-216.
AF Action Initiative Video Interview: NATF Board Member John Fanikos, RPh, MBA, discusses medication adherence and cost effectiveness with the treatment of atrial fibrillation.