| Literature DB >> 34413661 |
Taru Hallinen1, Erkki Soini1, Christian Asseburg1, Miika Linna2, Pia Eloranta3, Sari Sintonen3, Mikko Kosunen3.
Abstract
PURPOSE: Direct oral anticoagulant (DOAC) use for the prevention of thromboembolic complications in patients with non-valvular atrial fibrillation (AF) has increased steadily in Finland. DOACs have been shown to be cost-effective in comparison to warfarin, but published evidence of relative cost-effectiveness between DOACs is still scarce and mostly based on indirect comparisons of clinical trial evidence. The aim of this study was to compare the cost-effectiveness of apixaban to dabigatran, rivaroxaban and warfarin in a Finnish setting using real-life evidence where available. PATIENTS AND METHODS: A lifetime Markov simulation model used previously in a published Finnish assessment comparing apixaban and warfarin was modified and updated with the relative effectiveness and safety data available from the real-world NAXOS-study and representative Finnish input data for patient characteristics, event risks, mortality, resource use, costs, and quality of life. Apixaban's cost-effectiveness was assessed from health care payer perspective (using 3% per year discount rate) based on incremental cost-effectiveness ratio (ICER, cost per quality-adjusted life year [QALY] gained), probability of cost-effectiveness (at willingness-to-pay [WTP] of 35,000 euros/QALY), and net monetary benefit (NMB).Entities:
Keywords: apixaban; cost-utility; dabigatran; economic evaluation; rivaroxaban; warfarin
Year: 2021 PMID: 34413661 PMCID: PMC8370583 DOI: 10.2147/CEOR.S317078
Source DB: PubMed Journal: Clinicoecon Outcomes Res ISSN: 1178-6981
Figure 1Schematic presentation of the model. *Mild, moderate or severe, #transient state (ie, the patients transit back to the previous health state after one cycle and either continue or discontinue anticoagulation treatment). Reproduced from Hallinen T, Soini EJ, Linna M, Saarni SI. Cost-effectiveness of apixaban and warfarin in the prevention of thromboembolic complications among atrial fibrillation patients. Springerplus. 2016;5(1):1354, under the terms of the creative commons attribution 4.0 international license ().18
Risk of Modeled Health Events According to Treatment
| Rate per 100 Patient Years | Hazard Ratio (95% CI) vs Apixaban | ||||
|---|---|---|---|---|---|
| Apixaban | No Treatment | Warfarin | Dabigatran | Rivaroxaban | |
| Strokea | 1.359b | 4.186 | 1.67 (1.54–1.79) | 1.08 (0.90–1.28) | 0.95 (0.87–1.03) |
| Intracranial hemorrhage | 0.249b | 0 | 2.38 (2.08–2.70) | 1.02 (0.62–1.68) | 1.15 (0.99–1.33) |
| Other major bleed | 1.603c | 0 | 2.33 (2.17–2.50) | 1.08 (0.93–1.24) | 1.49 (1.39–1.59) |
| Clinically relevant non-major bleed | 2.090d | 0 | 1.433 (1.241–1.655)d | 1.00 (0.900–1.100) | 1.52 (1.28–1.80) |
| Myocardial infarction | 1.654e | 1.003 | 1.149 | 1.460 (0.960–2.200) | 1.060 (0.730–1.520) |
| Systemic embolisma | 0.060f | 0.956 | 1.67 (1.54–1.79) | 1.08 (0.90–1.28) | 0.95 (0.87–1.03) |
| Other CV hospitalizationsg | 10.46 | 16.506 | 1.00 | 1.00 | 1.00 |
| Treatment discontinuation for non-event related reasons | 13.107d | 1.10 (1.04–1.16)d | 1.50 (1.36–1.67) | 1.18 (1.08–1.61) | |
Notes: aAssumed equal to stroke and systemic embolism. bTotal number of events among 16,741 Finnish AF patients using warfarin were 375 for stroke and 99 for ICH.31 Assuming a full follow-up of one year for each patient, these were converted to a rate per 100 patient-years: 2.27 and 0.59, respectively. cTotal number of bleeding events in 125,261 Finnish patients using warfarin was 5412,32 and the corresponding rate was 4.32 per 100 patient-years. By subtracting the ICH rate from total bleeds, the rate for other major bleeds was estimated at 3.73 per 100 patient-years. dSecondary analysis of ARISTOTLE-trial. e1.900 per 100 patient-years for warfarin.33 f0.1 per 100 patient-years for warfarin.8 gSecondary analysis of AVERROES-trial, all treatments assumed equal.
Costs and Quality of Life Inputs
| Costb | Utility | |
|---|---|---|
| Apixaban 2.5 or 5 mg, twice a day | 2.53 | |
| Dabigatran 110 or 150 mg, twice a day | 2.58 | |
| Rivaroxaban 20 mg, once a day | 2.59 | |
| Warfarin 5 mg | 0.10 | |
| General physician visit | 119.97 | |
| INR-monitoring, warfarin only (Nurse visit and INR-test) | 64.85 | |
| Laboratory testsc | 13.20 | |
| 0.743 | ||
| Mild | −0.087 | |
| Acute Care | 4543.12 | |
| Long-term Maintenance | 0 | |
| Moderate | −0.198 | |
| Acute Care | 7719.71 | |
| Long-term Maintenance | 967.57 | |
| Severe | −0.644 | |
| Acute Care | 7725.75 | |
| Long-term Maintenance | 4403.61 | |
| Fatal | 5475.59 | |
| Mild | −0.071 | |
| Acute Care | 2696.51 | |
| Long-term Maintenance | 2696.51 | |
| Moderate | −0.352 | |
| Acute Care | 9455.08 | |
| Long-term Maintenance | 2183.41 | |
| Severe | −0.578 | |
| Acute Care | 9641.27 | |
| Long-term Maintenance | 3818.62 | |
| Fatal | 5708.06 | |
| −0.084 | ||
| Acute Care | 2125.68 | |
| Long-term Maintenance | 106.76 | |
| 4366.50 | −0.168 | |
| −0.168 | ||
| GI Bleeds | 3537.48 | |
| Non-ICH and Non-GI Related Major Bleeds | 3537.48 | |
| 2058.10 | −0.0582 | |
| −0.005 | ||
| Acute Care | 5453.00 | |
| Long-term Maintenance | 538.50 | |
| 3774.93 | ||
| Dyspepsiad | 125.49 |
Notes: aDrug costs were assessed based on the cost of the reimbursed price of the pack with approximately one-month supply for each product in 2/2021.37 bConversion from previous years (to year 2019 real values) were made using the communal health care price index by statistics Finland.38 cBasic blood count, thrombocytes, creatinine, estimated glomerular filtration rate, alanine aminotransferase.39 dAssumption: GP visit, pantoprazole 20 mg 100 tablets. The proportion of patients experiencing dyspepsia was obtained from the respective clinical trials and were 1.7% for apixaban and rivaroxaban, 3.5% for dabigatran, and 1.8% for warfarin.
Results of the Cost-Effectiveness Analysis
| LY | QALY | Costs | Difference, Apixaban vs Comparator | ICER (€/QALY) | ||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Total | Monitoring | Event | Drug | Cost | LY | QALY | ||||
| Apixaban | 8.37 | 6.09 | 18,342 | 1068 | 13,356 | 3918 | ||||
| Rivaroxaban | 8.32 | 6.05 | 18,385 | 1057 | 13,703 | 3625 | −43 | 0.05 | 0.03 | Apixaban dominates |
| Dabigatran | 8.23 | 5.98 | 18,746 | 1046 | 14,588 | 3112 | −404 | 0.13 | 0.11 | Apixaban dominates |
| Warfarin | 8.22 | 5.94 | 22,033 | 5877 | 16,008 | 149 | −3691 | 0.15 | 0.14 | Apixaban dominates |
Figure 2The cost-effectiveness plane for apixaban versus (A) warfarin, (B) dabigatran and (C) rivaroxaban. Green line depicts ICER threshold of 35,000 euros per QALY gained. The points lying below the line represent the simulations where apixaban was either cost-effective or dominating (South-West quadrant) versus its comparator.
Figure 3The cost-effectiveness acceptability curve for apixaban versus warfarin, dabigatran and rivaroxaban.
Results of the Deterministic Sensitivity Analyses
| Scenario | Treatment | QALY | Costs | Net Cost | Net QALY | ICER (€/QALY), Apixaban vs Comparator |
|---|---|---|---|---|---|---|
| No discounting | Apixaban | 7.34 | 22,511 | |||
| Rivaroxaban | 7.30 | 22,553 | −42 | 0.04 | Apixaban dominates | |
| Dabigatran | 7.20 | 22,951 | −440 | 0.14 | Apixaban dominates | |
| Warfarin | 7.15 | 26,769 | −4257 | 0.19 | Apixaban dominates | |
| 5-year timeframe | Apixaban | 3.06 | 8028 | |||
| Rivaroxaban | 3.05 | 8095 | −68 | 0.01 | Apixaban dominates | |
| Dabigatran | 3.04 | 8298 | −270 | 0.02 | Apixaban dominates | |
| Warfarin | 3.03 | 10,263 | −2235 | 0.04 | Apixaban dominates | |
| Retail prices, largest available pack | Apixaban | 6.09 | 18,342 | |||
| Rivaroxaban | 6.05 | 18,063 | 279 | 0.03 | 8978 | |
| Wholesale prices, largest available pack | Apixaban | 6.09 | 17,329 | |||
| Rivaroxaban | 6.05 | 17,438 | −109 | 0.03 | Apixaban dominates | |
| Dabigatran | 5.98 | 17,837 | −507 | 0.11 | Apixaban dominates | |
| Warfarin | 5.94 | 21,987 | −4658 | 0.14 | Apixaban dominates | |
| Warfarin monitoring cost reduceda | Apixaban | 6.09 | 18,342 | |||
| Warfarin | 5.94 | 19,166 | −824 | 0.14 | Apixaban dominates |
Notes: aPhone call, 13.08 euros, instead of a nurse visit. Dominates = more effective, less costly.
Abbreviations: AF, atrial fibrillation; DOAC, direct oral anticoagulant; GI, gastrointestinal; HS, hemorrhagic stroke; ICH, intracranial hemorrhage; ICER, incremental cost-effectiveness ratio; IS, ischemic stroke; MI, myocardial infarction; NMB, net monetary benefit; SE, systemic embolism; PSA, probabilistic sensitivity analysis; QALY, quality-adjusted life-year; WTP, willingness-to-pay.