Top

The European Journal of Health Economics

Published in:

17-05-2023 | Stroke | Original Paper

Does prescribing apixaban or rivaroxaban versus warfarin for patients diagnosed with atrial fibrillation save health system costs? A multivalued treatment effects analysis

Authors: Michael Situ, Ute I. Schwarz, Guangyong Zou, Eric McArthur, Richard B. Kim, Amit X. Garg, Sisira Sarma

Published in: The European Journal of Health Economics | Issue 3/2024

Abstract

Background

Non-valvular atrial fibrillation (AF) is a common heart arrhythmia in the elderly population. AF patients are at high-risk of ischemic strokes, but oral anticoagulant (OAC) therapy reduces such risks. Warfarin had been the standard OAC for AF patients, however its effectiveness is highly variable and dependent on close monitoring of the anticoagulant response. Newer OACs such as rivaroxaban and apixaban address these drawbacks but are more costly. It is uncertain which OAC therapy for AF is cost-saving from the healthcare system perspective.

Methods

We followed a cohort of patients in Ontario, Canada, aged ≥ 66 who were newly diagnosed with AF and prescribed OACs between 2012 and 2017. We used a two-stage estimation procedure. First, we account for the patient selection into OACs using a multinomial logit regression model and estimated propensity scores. Second, we used an inverse probability weighted regression adjustment approach to determine cost-saving OAC options. We also examined component-specific costs (i.e., drug, hospitalization, emergency department and physician) to understand the drivers of cost-saving OACs.

Results

We found that compared to warfarin, rivaroxaban and apixaban treatments were cost-saving options, with per-patient 1-year healthcare cost savings at $2436 and $1764, respectively. These savings were driven by cost-savings in hospitalization, emergency department visits, and physician visits, outweighing higher drug costs. These results were robust to alternative model specifications and estimation procedures.

Conclusions

Treating AF patients with rivaroxaban and apixaban than warfarin reduces healthcare costs. OAC reimbursement policies for AF patients should consider rivaroxaban or apixaban over warfarin as the first-line treatment.

Available only for authorised users

Lippi, G., Sanchis-Gomar, F., Cervellin, G.: Global epidemiology of atrial fibrillation: an increasing epidemic and public health challenge. Int. J. Stroke 16, 217–221 (2021). https://doi.org/10.1177/1747493019897870CrossRefPubMed

Heart and Stroke Foundation of Canada: Heart disease—atrial fibrillation. https://www.heartandstroke.ca/heart-disease/conditions/atrial-fibrillation

Wolf, P.A., Abbott, R.D., Kannel, W.B.: Atrial fibrillation as an independent risk factor for stroke: the framingham study. Stroke 22, 983–988 (1991). https://doi.org/10.1161/01.STR.22.8.983CrossRefPubMed

Andrew, N.E., Thrift, A.G., Cadilhac, D.A.: The prevalence, impact and economic implications of atrial fibrillation in stroke: what progress has been made? Neuroepidemiology 40, 229–239 (2013). https://doi.org/10.1159/000343667CrossRef

Humphries, K.H., Jackevicius, C., Gong, Y., Svensen, L., Cox, J., Tu, J.V., Laupacis, A.: Population rates of hospitalization for atrial fibrillation/flutter in Canada. Can. J. Cardiol. 20, 869–876 (2004)PubMed

O’Reilly, D.J., Hopkins, R.B., Healey, J.S., Dorian, P., Sauriol, L., Tarride, J.E., Burke, N., Goeree, R.A.: The burden of atrial fibrillation on the hospital sector in Canada. Can. J. Cardiol. 29, 229–235 (2013). https://doi.org/10.1016/j.cjca.2012.03.023CrossRefPubMed

De Caterina, R., Husted, S., Wallentin, L., Andreotti, F., Arnesen, H., Bachmann, F., Baigent, C., Huber, K., Jespersen, J., Kristensen, S.D., Lip, G.Y.H., Morais, J., Rasmussen, L.H., Siegbahn, A., Verheugt, F.W.A., Weitz, J.I.: Vitamin K antagonists in heart disease: current status and perspectives (section III): Position paper of the ESC working group on thrombosis—task force on anticoagulants in heart disease. Thromb. Haemost. 110, 1087–1107 (2013). https://doi.org/10.1160/TH13-06-0443CrossRefPubMed

Ogilvie, I.M., Newton, N., Welner, S.A., Cowell, W., Lip, G.Y.H.: Underuse of oral anticoagulants in atrial fibrillation: a systematic review. Am. J. Med. (2010). https://doi.org/10.1016/j.amjmed.2009.11.025CrossRefPubMed

Steinberg, B.J., Piccini, J.P.: Anticoagulation in atrial fibrillation. BMJ (2014). https://doi.org/10.1136/bmj.g2116CrossRefPubMedPubMedCentral

10.

Patel, M.R., Mahaffey, K.W., Garg, J., Pan, G., Singer, D.E., Hacke, W., Breithardt, G., Halperin, J.L., Hankey, G.J., Piccini, J.P., Becker, R.C., Nessel, C.C., Paolini, J.F., Berkowitz, S.D., Fox, K.A.A., Califf, R.M., the ROCKET AF Steering Committee, for the R.A.I.: Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N. Engl. J. Med. 365, 883–891 (2011). https://doi.org/10.1056/NEJMoa1109071CrossRefPubMed

11.

Granger, C., Alexander, J.H., McMurray, J.J., Lopes, R.D., Hylek, E.M., Hanna, M., Al-Khalidi, H.R., Ansell, J., Atar, D., Avezum, A., Bahit, C.M., Diaz, R., Easton, D.J., Ezekowitz, J.A., Flaker, G., Garcia, D., Geraldes, M., Gersh, B.J., Golitsyn, M., Goto, S., Hermosillo, A.G., Hohnloser, S.H., Horowitz, J., Mohan, P., Jansky, P., Lewis, B.S., Lopez-Sendon, J.L., Parkhomenko, A., Verheugt, F.W.A., Zhu, J., Wallentin, L.: Apixaban versus warfarin in patients with atrial fibrillation. N. Engl. J. Med. 365, 981–992 (2011). https://doi.org/10.1056/NEJMoa1107039CrossRefPubMed

12.

Xu, Y., Holbrook, A.M., Simpson, C.S., Dowlatshahi, D., Johnson, A.P.: Prescribing patterns of novel oral anticoagulants following regulatory approval for atrial fibrillation in Ontario, Canada: a population-based descriptive analysis. Can. Open 1, E115–E119 (2013). https://doi.org/10.9778/cmajo.20130032CrossRef

13.

Wan, D., Healey, J.S., Simpson, C.S.: The guideline-policy gap in direct-acting oral anticoagulants usage in atrial fibrillation: evidence, practice, and public policy considerations. Can. J. Cardiol. 34, 1412–1425 (2018). https://doi.org/10.1016/j.cjca.2018.07.476CrossRefPubMed

14.

Wodchis, W.P., Bushmeneva, K., Nikitovic, M., McKillop, I., Guidelines on person-level costing using administrative databases in Ontario (2013)

15.

Statistics Canada: CANSIM Table 326-0021 Consumer Price Index, annual average, not seasonally adjusted. http://www5.statcan.gc.ca/cansim/a26?lang=eng&retrLang=eng&id260021&tabModeÚtaTable&srchLan=-1&p1=-1&p2=9

16.

Hosmer, D.W., Lemeshow, S., Sturdivant, R.X.: Logistic regression models for multinomial and ordinal outcomes. In: Balding, D.J., Cressie, N.A., Fitzmaurice, G.M., Goldstein, H., Johnstone, I.M., Molenberghs, G., Scott, D.W., Smith, A.F.M., Tsay, R.S., Weisberg, S. (eds.) Applied Logistic Regression, pp. 269–311. Wiley, Hoboken (2013)CrossRef

17.

Słoczyński, T., Wooldridge, J.M.: A general double robustness result for estimating average treatment effects. Econom. Theory. 34, 112–133 (2018). https://doi.org/10.1017/S0266466617000056CrossRef

18.

Derya Uysal, S.: Doubly robust estimation of causal effects with multivalued treatments: an application to the returns to schooling. J. Appl. Econom. 30, 763–786 (2015). https://doi.org/10.1002/jae.2386CrossRef

19.

Cattaneo, M.D.: Efficient semiparametric estimation of multi-valued treatment effects under ignorability. J. Econom. 155, 138–154 (2010). https://doi.org/10.1016/j.jeconom.2009.09.023CrossRef

20.

Austin, P.C.: Balance diagnostics for comparing the distribution of baseline covariates between treatment groups in propensity-score matched samples. Stat. Med. 28, 3083–3107 (2009). https://doi.org/10.1002/sim.3697CrossRefPubMedPubMedCentral

21.

Zhang, Z., Kim, H.J., Lonjon, G., Zhu, Y.: Balance diagnostics after propensity score matching. Ann. Transl. Med. 7(1), 16 (2019). https://doi.org/10.21037/atm.2018.12.10CrossRefPubMedPubMedCentral

22.

Amin, A., Keshishian, A., Vo, L., Zhang, Q., Dina, O., Patel, C., Odell, K., Trocio, J.: Real-world comparison of all-cause hospitalizations, hospitalizations due to stroke and major bleeding, and costs for non-valvular atrial fibrillation patients prescribed oral anticoagulants in a US health plan. J. Med. Econ. 21, 244–253 (2018). https://doi.org/10.1080/13696998.2017.1394866CrossRefPubMed

23.

Laliberté, F., Cloutier, M., Crivera, C., Nelson, W.W., Olson, W.H., Schein, J., Vanderpoel, J., Germain, G., Lefebvre, P.: Effect of rivaroxaban versus warfarin on health care costs among nonvalvular atrial fibrillation patients: observations from rivaroxaban users and matched warfarin users. Adv. Ther. 32, 216–227 (2015). https://doi.org/10.1007/s12325-015-0189-1CrossRefPubMedPubMedCentral

24.

Amin, A., Keshishian, A., Trocio, J., Dina, O., Le, H., Rosenblatt, L., Liu, X., Mardekian, J., Zhang, Q., Baser, O., Nadkarni, A., Vo, L.: A real-world observational study of hospitalization and health care costs among nonvalvular atrial fibrillation patients prescribed oral anticoagulants in the U.S. Medicare population. J. Manag. Care Spec. Pharm. 26, 639–651 (2020). https://doi.org/10.18553/jmcp.2020.26.5.639CrossRefPubMed

25.

Lin, J., Trocio, J., Gupta, K., Mardekian, J., Lingohr-Smith, M., Menges, B., You, M., Nadkarni, A.: Major bleeding risk and healthcare economic outcomes of non-valvular atrial fibrillation patients newly-initiated with oral anticoagulant therapy in the real-world setting. J. Med. Econ. 20, 952–961 (2017). https://doi.org/10.1080/13696998.2017.1341902CrossRefPubMed

26.

Li, X., Deitelzweig, S., Keshishian, A., Hamilton, M., Horblyuk, R., Gupta, K., Luo, X., Mardekian, J., Friend, K., Nadkarni, A., Pan, X., Lip, G.Y.H.: Effectiveness and safety of apixaban versus warfarin in non-valvular atrial fibrillation patients in “real-world” clinical practice: a propensity-matched analysis of 76,940 patients. Thromb. Haemost. 117, 1072–1082 (2017). https://doi.org/10.1160/TH17-01-0068CrossRefPubMedPubMedCentral

27.

Laliberté, F., Pilon, D., Raut, M.K., Nelson, W.W., Olson, W.H., Germain, G., Schein, J.R., Lefebvre, P.: Is rivaroxaban associated with lower inpatient costs compared to warfarin among patients with non-valvular atrial fibrillation? Curr. Med. Res. Opin. 30, 1521–1528 (2014). https://doi.org/10.1185/03007995.2014.916159CrossRefPubMed

28.

Gupta, K., Trocio, J., Keshishian, A., Zhang, Q., Dina, O., Mardekian, J., Nadkarni, A., Shank, T.C.: Effectiveness and safety of direct oral anticoagulants compared to warfarin in treatment naïve non-valvular atrial fibrillation patients in the US Department of defense population. BMC Cardiovasc. Disord. 19, 1–10 (2019). https://doi.org/10.1186/s12872-019-1116-1CrossRef

29.

Belhassen, M., Hanon, O., Steg, P., Mahé, I., Née, M., Jacoud, F., Dalon, F., Cotté, F., Guitard-Dehoux, D., Marant-Micallef, C., Van Ganse, E., Danchin, N.: Apixaban versus other anticoagulants in patients with nonvalvular fibrillation: a comparison of all-cause and event-related costs in real-life setting in France. Eur. J. Health Econ. (2022). https://doi.org/10.1007/s10198-022-01513-2CrossRefPubMedPubMedCentral

30.

Milentijevic, D., Germain, G., Laliberté, F., Bookhart, B.K., MacKnight, S.D., Tsang, J., Lefebvre, P.: Healthcare costs of NVAF patients treated with rivaroxaban and apixaban in the US. J. Med. Econ. 23, 1365–1374 (2020). https://doi.org/10.1080/13696998.2020.1821038CrossRefPubMed

31.

Heinze, G., Wallisch, C., Dunkler, D.: Variable selection—a review and recommendations for the practicing statistician. Biom. J. 60, 431–449 (2018). https://doi.org/10.1002/bimj.201700067CrossRefPubMedPubMedCentral

32.

Lip, G.Y.H., Nieuwlaat, R., Pisters, R., Lane, D.A., Crijns, H.J.G.M.: Refining clinical risk stratification for predicting stroke and thromboembolism in atrial fibrillation using a novel risk factor-based approach: the Euro Heart Survey on atrial fibrillation. Chest 137, 263–272 (2010). https://doi.org/10.1378/chest.09-1584CrossRefPubMed

33.

Pisters, R., Lane, D.A., Nieuwlaat, R., De Vos, C.B., Crijns, H.J.G.M., Lip, G.Y.H.: A novel user-friendly score (HAS-BLED) to assess 1-year risk of major bleeding in patients with atrial fibrillation: the Euro Heart Survey. Chest 138, 1093–1100 (2010). https://doi.org/10.1378/chest.10-0134CrossRefPubMed

34.

Skanes, A.C., Healey, J.S., Cairns, J.A., Dorian, P., Gillis, A.M., McMurtry, M.S., Mitchell, L.B., Verma, A., Nattel, S.: Focused 2012 update of the Canadian Cardiovascular Society atrial fibrillation guidelines: recommendations for stroke prevention and rate/rhythm control. Can. J. Cardiol. 28, 125–136 (2012). https://doi.org/10.1016/j.cjca.2012.01.021CrossRefPubMed

35.

Griffin, B.A., Stelzner, C., Sanchez, R., Cefalu, M., McCaffrey, D.: Toolkit for Weighting and Analysis of Nonequivalent Groups: A Tutorial on the TWANG Shiny Application for Three or More Treatment Groups. RAND Corporation (2020)

36.

Mccaffrey, D.F., Griffin, B.A., Almirall, D., Slaughter, M.E., Ramchand, R., Burgette, L.F.: A tutorial on propensity score estimation for multiple treatments using generalized boosted models. Stat. Med. 32, 3388–3414 (2013). https://doi.org/10.1002/sim.5753CrossRefPubMedPubMedCentral

37.

Allan, D.E., Funk, L.M., Reid, R.C., Cloutier-Fisher, D.: Exploring the influence of income and geography on access to services for older adults in British Columbia: a multivariate analysis using the Canadian community health survey (Cycle 31). Can. J. Aging. 30, 69–82 (2011). https://doi.org/10.1017/S0714980810000760CrossRefPubMed

38.

Schäfer, A., Flierl, U., Berliner, D., Bauersachs, J.: Anticoagulants for stroke prevention in atrial fibrillation in elderly patients. Cardiovasc. Drugs Ther. 34, 555–568 (2020). https://doi.org/10.1007/s10557-020-06981-3CrossRefPubMedPubMedCentral

39.

Hylek, E.M., Evans-Molina, C., Shea, C., Henault, L.E., Regan, S.: Major hemorrhage and tolerability of warfarin in the first year of therapy among elderly patients with atrial fibrillation. Circulation 115, 2689–2696 (2007). https://doi.org/10.1161/CIRCULATIONAHA.106.653048CrossRefPubMed

Title: Does prescribing apixaban or rivaroxaban versus warfarin for patients diagnosed with atrial fibrillation save health system costs? A multivalued treatment effects analysis
Authors: Michael Situ
Ute I. Schwarz
Guangyong Zou
Eric McArthur
Richard B. Kim
Amit X. Garg
Sisira Sarma
Publication date: 17-05-2023
Publisher: Springer Berlin Heidelberg
Keywords: Stroke
Anticoagulant
Care
Oral Anticoagulant
Atrial Fibrillation
Apixaban
Warfarin
Rivaroxaban
Published in: The European Journal of Health Economics / Issue 3/2024
Print ISSN: 1618-7598
Electronic ISSN: 1618-7601
DOI: https://doi.org/10.1007/s10198-023-01594-7

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Does prescribing apixaban or rivaroxaban versus warfarin for patients diagnosed with atrial fibrillation save health system costs? A multivalued treatment effects analysis

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 3/2024

Excess healthcare expenditure in adults treated for solid cancer in childhood: a cohort study in France

A cost-of-illness study of Behçet syndrome in Italy

Self-interest, positional concerns and distributional considerations in healthcare preferences

Cost-effectiveness of transcatheter aortic valve implantation in patients at low surgical risk in France: a model-based analysis of the Evolut LR trial

Mapping from SIBDQ to EQ-5D-5L for patients with inflammatory bowel disease

The link between physician motivation and care