1. Is it time to replace warfarin with novel oral
anticoagulants (NOACs) for treating thrombotic disorders?
Charles Ng, C. Daniel Mullins, PhD
References
Background
• Warfarin has been the gold standard for venous thromboembolism (VTE)
treatment and stroke/systemic embolism prophylaxis in patients with
nonvalvular atrial fibrillation (NVAF) for the past 50 years.1,2
• Within the past few years, NOACs such as edoxaban, apixaban,
rivaroxaban, and dabigatran have emerged as the preferred treatment
due to their favorable pharmacokinetics, pharmacodynamics, and
minimal adverse events.1,2
Objective
• A decision tree was constructed for each of the indications: VTE
treatment and stroke/systemic embolism prophylaxis in NVAF patients.
• Each tree compared five therapies: edoxaban, apixaban, rivaroxaban,
dabigatran, and warfarin.
• The transition probabilities were derived from their respective phase 3
clinical trials.
• Costs were derived from various literature sources with a one-year time
frame.
Methods
Model Inputs
Clinical Trial Summary
To determine the cost-effectiveness of the NOACs versus warfarin from a
managed care organization (MCO) perspective.
Decision Tree
Table 1. VTE clinical efficacy and safety summaries derived from NOAC’s respective phase 3 trials
Table 2. NVAF clinical efficacy and safety summaries derived from NOAC’s respective phase 3 clinical trials
Table 4. Data derived from NOAC’s respective phase 3 clinical trials and various literature sources
Table 3. Data derived from NOAC’s respective phase 3 clinical trials and various literature sources
CRNMB: Clinically relevant non-major bleeding
Results: NVAF Treatment
Conclusions
Contact
• Apixaban had the lowest average yearly cost of $7,755.91, followed
by warfarin ($7,864.46), dabigatran ($8,903.02), edoxaban
($9,557.37), and rivaroxaban ($10,630.41).
• Effectiveness was measured by treatment response without a major
bleeding or CRNMB event. Warfarin had the lowest efficacy of 0.87,
followed by rivaroxaban (0.88), edoxaban (0.89), dabigatran (0.91),
and apixaban (0.94).
• For VTE treatment, apixaban is the most cost-effective option due
to its superior price and efficacy profile, therefore it should be
added to the MCO formulary for this indication.
• For stroke/systemic embolism prophylaxis in NVAF patients,
apixaban is the most efficacious option, but warfarin is the least
expensive option.
• From a cost effectiveness viewpoint, warfarin should not be
replaced by the NOACs because it demonstrates good value, but for
those seeking the most efficacious treatment, apixaban should be
the drug of choice.
1. Venous Thromboembolism (Blood Clots) [Internet]. [cited 2016 May 4]. Available from: http://www.cdc.gov/ncbddd/dvt/data.html
2. Atrial Fibrillation Fact Sheet [Internet]. [cited 2016 May 4]. Available from: http://www.cdc.gov/dhdsp/data_statistics/fact_sheets/fs_atrial_fibrillation.htm
3. Hokusai-VTE Investigators, Büller HR, Décousus H, et al. Edoxaban versus Warfarin for the Treatment of Symptomatic Venous Thromboembolism. N Engl J Med. 2013, Oct 10:
369:1406-1415. Available at: http://www.nejm.org/doi/pdf/10.1056/NEJMoa1306638
4. Agnelli G, Buller HR, Cohen A, et al. Oral Apixaban for the Treatment ofAcute Venous Thromboembolism. N Engl J Med. 2013, Aug 29: 369:799-808. Available at:
http://www.nejm.org/doi/pdf/10.1056/NEJMoa1302507
5. Prins et al.: Oral rivaroxaban versus standard therapy for the treatment of symptomatic venous thromboembolism: a pooled analysis of the EINSTEIN-DVT and PE randomized
studies. Thrombosis Journal 2013 11:21
6. Schulman S, Kearon C, Kakkar AK, et al. Dabigatran versus Warfarin in the Treatment ofAcute Venous Thromboembolism. N Engl J Med. 2009, Dec 10: 2342-52. Available at:
http://www.nejm.org/doi/pdf/10.1056/NEJMoa0906598
7. Giugliano RP, Ruff CT, Braunwald E, et al. Edoxaban versus Warfarin in Patients with Atrial Fibrillation. N Engl J Med. 2013, Nov 28: 369:2093-2104. Available at:
http://www.nejm.org/doi/full/10.1056/NEJMoa1310907
8. Granger CB,Alexander JH, McMurray JJ, et al.Apixaban versus Warfarin in Patients with Atrial Fibrillation. N Engl J Med. 2011, Sep 15: 365:981-992. Available at:
http://www.nejm.org/doi/full/10.1056/NEJMoa1107039
9. Patel MR, Mahaffey KW, Garg J, et al. Rivaroxaban versus Warfarin in Nonvalvular Atrial Fibrillation. N Engl J Med. 2011, Sep 8: 365:883-891. Available at:
http://www.nejm.org/doi/full/10.1056/NEJMoa1009638
10.Connolly SJ, Ezekowitz MD, Phil D, et al. Dabigatran versus Warfarin in Patients with Atrial Fibrillation. N Engl J Med. 2009, Sep 7: 361:1139-1151. Available at:
http://www.nejm.org/doi/full/10.1056/NEJMoa0905561
11.Amin A, Lingohr-Smith M, BrunoA, Trocio J, Lin J (2015) Economic Evaluations of Medical Cost Differences: Use of Targeted-Specific Oral Anticoagulants vs. Warfarin among
Patients with Nonvalvular Atrial Fibrillation and Venous Thromboembolism in the U.S. J Hematol Thrombo Dis 3: 209. doi:10.4172/2329-8790.1000209
12.Biskupiak J, Ghate SR, Jiao T, et al. Cost implications of formulary decisions on oral anticoagulants in nonvalvular atrial fibrillation. J Manag Care Pharm. 2013 Nov-
Dec;19(9):789-98. Available at: http://www.amcp.org/WorkArea/DownloadAsset.aspx?id=17308
13.Magnuson EA, Vilain K, Wang K, et al. Cost-effectiveness of edoxaban vs warfarin in patients with atrial fibrillation based on results of the ENGAGE AF-TIMI 48 trial. Am Heart J.
2015 Dec;170(6):1140-50. Available at: https://www.ncbi.nlm.nih.gov/pubmed/26678636
14.Amin A, Lingohr-Smith M, BrunoA, Trocio J, Lin J (2015) Economic Evaluations of Medical Cost Differences: Use of Targeted-Specific Oral Anticoagulants vs. Warfarin among
Patients with Nonvalvular Atrial Fibrillation and Venous Thromboembolism in the U.S.. J Hematol Thrombo Dis 3: 209. doi:10.4172/2329-8790.1000209
15.REDBOOK [Internet]. Greenwood Village, Colorado: Thomson Reuters (Healthcare) Inc. 1974 – [cited 2016 Apr 26]. Available from http://www.micromedexsolutions.com/proxy-
hs.researchport.umd.edu/micromedex2/librarian/CS/8840FB/ND_PR/evidencexpert/ND_P/evidencexpert/DUPLICATIONSHIELDSYNC/D7A020/ND_PG/evidencexpert/ND_B/evid
encexpert/ND_AppProduct/evidencexpert/ND_T/evidencexpert/PFActionId/redbook.FindRedBook?navitem=topRedBook&isToolPage=true
Charles Ng: CharlesNg58@gmail.com; 443-939-8431; www.linkedin.com/in/CharlesNg58
Results: VTE Treatment
• Warfarin had the lowest average yearly cost of $1,119.71, followed
by edoxaban ($3,596.70), dabigatran ($4,110.33), apixaban
($4,385.71), and rivaroxaban ($4,438.61).
• The effectiveness was treatment response without a major
bleeding event. Warfarin and edoxaban had the lowest efficacy of
0.90, followed by rivaroxaban (0.91), dabigatran (0.92), and
apixaban (0.94).
• The incremental cost-effectiveness ratio of dabigatran versus
warfarin and apixaban versus dabigatran was $175,918.82 and
$12,517.27 per additional treatment response without a major
bleeding event, respectively.
Presented at Academy of Managed Care Pharmacy (AMCP) Nexus 2016 at the Gaylord National Resort & Convention Center in Washington, DC, October 4-5, 2016