Cost-Effectiveness Analysis of Direct Oral Anticoagulants Vs. Vitamin K Antagonists in the Elderly With Atrial Fibrillation: Insights From the Evidence in a Real-World Setting

Background: In the clinical setting, the economic benefits of direct oral anticoagulants (DOACs) in elderly patients with atrial fibrillation (AF) remain unclear. This study aimed to estimate and compare the cost-effectiveness of DOACs (dabigatran, rivaroxaban, apixaban, and edoxaban) and vitamin K antagonists (VKAs; warfarin) in preventing stroke among AF patients aged >75 years in real-world practice.Methods: A Markov model with a 10-year span was constructed to estimate the long-term clinical and economic outcomes among AF patients aged >75 years treated with DOACs and warfarin. The study was populated with a hypothetical cohort of 10,000 AF patients aged >75 years. Probabilities of clinical outcomes were obtained from the pooled observational studies (OSs), comparing DOACs (dabigatran, rivaroxaban, apixaban, and edoxaban) with VKAs. Other model inputs, including the utilities and the costs, were all estimated from public sources and the published literature. The costs, quality-adjusted life-years (QAYLs), and incremental cost-effectiveness ratios (ICER) were estimated for each treatment strategy. Subgroup analyses of individual DOACs and the scenario analysis were performed. Uncertainty was evaluated by deterministic sensitivity analysis and probabilistic sensitivity analysis (PSA).Results: Compared to warfarin, DOACs were associated with a gain of 0.36 QALY at an additional cost of $15,234.65, resulting in an ICER of $42,318.47 per QALY. Sensitivity analysis revealed that the ICER was sensitive to the cost of DOACs. Direct oral anticoagulants also shifted from dominating to dominated status When their annual costs of DOACs were over $3,802.84 or the risk ratio of death compared to warfarin was over 1.077%/year. Probabilistic sensitivity analysis (PSA) suggested that DOACs had a 53.83 and 90.7% probability of being cost-effective when the willingness-to-pay threshold was set at $50,000 and $100,000, respectively. Among all the four individual DOACs, edoxaban treatment was revealed as the preferred treatment strategy for the AF patients aged over 75 years by yielding the most significant health gain with the relatively low total cost.Conclusions: Despite the high risk for major bleeding in elderly patients with AF, DOACs are more cost-effective treatment options than warfarin in real-world practice. Edoxaban was the preferred treatment strategy among four kinds of DOACs for AF patients aged over 75 years. Furthermore, beyond their safety profiles, the treatment benefits of DOACs assumed greater relevance and importance in older adults.

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Economic evaluation of direct oral anticoagulants (DOACs) versus vitamin K antagonists (VKAs) for stroke prevention in patients with atrial fibrillation: a systematic review and meta-analysis

BMJ evidence-based medicine ◽

10.1136/bmjebm-2020-111634 ◽

2021 ◽

pp. bmjebm-2020-111634

Author(s):

Rini Noviyani ◽

Sitaporn Youngkong ◽

Surakit Nathisuwan ◽

Bhavani Shankara Bagepally ◽

Usa Chaikledkaew ◽

...

Keyword(s):

Atrial Fibrillation ◽

Systematic Review ◽

Economic Evaluation ◽

Cost Effectiveness ◽

Meta Analysis ◽

Vitamin K Antagonists ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Cost Effective ◽

Risk Of Bias

ObjectivesTo assess cost-effectiveness of direct oral anticoagulants (DOACs) compared with vitamin K antagonists (VKAs) for stroke prevention in atrial fibrillation (AF) by pooling incremental net benefits (INBs).DesignSystematic review and meta-analysis.SettingWe searched PubMed, Scopus and Centre for Evaluation of Value and Risks in Health Registry from inception to December 2019.ParticipantsPatients with AF.Main outcome measuresThe INB was defined as a difference of incremental effectiveness multiplied by willing to pay threshold minus the incremental cost; a positive INB indicated favour treatment. These INBs were pooled (stratified by level of country income, perspective, time-horizon, model types) with a random-effects model if heterogeneity existed, otherwise a fixed effects model was applied. Heterogeneity was assessed using Q test and I2 statistic. Risk of bias was assessed using the economic evaluations bias (ECOBIAS) checklist.ResultsA total of 100 eligible economic evaluation studies (224 comparisons) were included. For high-income countries (HICs) from a third-party payer (TPP) perspective, the pooled INBs for DOAC versus VKA pairs were significantly cost-effective with INBs (95% CI) of $6632 ($2961.67 to $10 303.72; I2=59.9%), $6353.24 ($4076.03 to $8630.45; I2=0%), $7664.58 ($2979.79 to $12 349.37; I2=0%) and $8573.07 ($1877.05 to $15 269.09; I2=0%) for dabigatran, apixaban, rivaroxaban and edoxaban relative to VKA, respectively but only dabigatran was significantly cost-effective from societal perspective (SP) with an INB of $11 746.96 ($2429.34 to $21 064.59; I2=52.4%). The pooled INBs of all comparisons for upper-middle income countries (UMICs) were not significantly cost-effective. The ECOBIAS checklist indicated that risk of bias was mostly low for most items with the exception of five items which should be less influenced on pooling INBs.ConclusionsOur meta-analysis provides comprehensive economic evidence that allows policy makers to generalise cost-effectiveness data to their local context. All DOACs may be cost-effective compared with VKA in HICs with TPP perspective. The pooling results produced moderate to high heterogeneity particularly in UMICs. Further studies are required to inform UMICs with SP.PROSPERO registeration numberCRD 42019146610.

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Direct Anticoagulants Versus Vitamin K Antagonists in Patients Aged 80 Years or Older With Atrial Fibrillation in a “Real-world” Nationwide Registry: Insights From the FANTASIIA Study

Journal of Cardiovascular Pharmacology and Therapeutics ◽

10.1177/1074248420916316 ◽

2020 ◽

Vol 25 (4) ◽

pp. 316-323

Author(s):

Martín Ruiz Ortiz ◽

Javier Muñiz ◽

María Asunción Esteve-Pastor ◽

Francisco Marín ◽

Inmaculada Roldán ◽

...

Keyword(s):

Atrial Fibrillation ◽

Vitamin K ◽

Real World ◽

Vitamin K Antagonists ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Left Ventricular ◽

Anticoagulant Treatment ◽

Cancer History

Objective: To describe major events at follow up in octogenarian patients with atrial fibrillation (AF) according to anticoagulant treatment: direct oral anticoagulants (DOACs) versus vitamin K antagonists (VKAs). Methods: A total of 578 anticoagulated patients aged ≥80 years with AF were included in a prospective, observational, multicenter study. Basal features, embolic events (stroke and systemic embolism), severe bleedings, and all-cause mortality at follow up were investigated according to the anticoagulant treatment received. Results: Mean age was 84.0 ± 3.4 years, 56% were women. Direct oral anticoagulants were prescribed to 123 (21.3%) patients. Compared with 455 (78.7%) patients treated with VKAs, those treated with DOACs presented a lower frequency of permanent AF (52.9% vs 61.6%, P = .01), cancer history (4.9% vs 10.9%, P = .046), renal failure (21.1% vs 32.2%, P = .02), and left ventricular dysfunction (2.4% vs 8.0%, P = .03); and higher frequency of previous stroke (26.0% vs 16.6%, P = .02) and previous major bleeding (8.1% vs 3.6%, P = .03). There were no significant differences in Charlson, CHA2DS2VASc, nor HAS-BLED scores. At 3-year follow up, rates of embolic events, severe bleedings, and all-cause death (per 100 patients-year) were similar in both groups (DOACs vs VKAs): 0.34 vs 1.35 ( P = .15), 3.45 vs 4.41 ( P = .48), and 8.2 vs 11.0 ( P = .18), respectively, without significant differences after multivariate analysis (hazard ratio [HR]: 0.25, 95% confidence interval [CI]: 0.03-1.93, P = .19; HR: 0.88, 95% CI: 0.44-1.76, P = .72 and HR: 0.84, 95% CI: 0.53-1.33, P = .46, respectively). Conclusion: In this “real-world” registry, the differences in major events rates in octogenarians with AF were not statistically significant in those treated with DOACs versus VKAs.

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Economic Evaluation of the Direct Oral Anticoagulants Compared to Vitamin K Antagonists in the Treatment of Deep Venous Thrombosis and Pulmonary Embolism in the Outpatient Setting: Analysis from the Queen Elizabeth II Health Sciences Centre in Halifax, Nova Scotia

Blood ◽

10.1182/blood.v128.22.3528.3528 ◽

2016 ◽

Vol 128 (22) ◽

pp. 3528-3528

Author(s):

Abdullah S. Al Saleh ◽

Patrick Berrigan ◽

David Anderson ◽

Sudeep Shivakumar

Keyword(s):

Cost Effectiveness ◽

Cost Minimization ◽

Vitamin K Antagonists ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Cost Effective ◽

Dominant Strategy ◽

Cost Effectiveness Analysis ◽

Cost Minimization Analysis ◽

Effectiveness Analysis

Abstract Background: To date, there have been few economic evaluations of the direct oral anticoagulants in the treatment of venous thromboembolism (VTE) conducted from a Canadian perspective. As a result, there is a lack of consensus within existing literature regarding which treatment strategy should be adopted into the clinical setting. To our knowledge, this is the first Canadian economic evaluation in patients with VTE who are treated solely on an outpatient basis. Objectives: We conducted a cost-minimization analysis to determine the least costly intervention for the prevention of recurrent venous thrombosis in patients with acute unprovoked VTE including apixaban, rivaroxaban, low molecular weight heparin (LMWH) in combination with dabigatran, and LMWH overlapped with vitamin K antagonists (VKA). We also conducted a cost-effectiveness analysis to assess value for money in terms of cost per quality adjusted life year (QALY) gained. Methods: We used Microsoft Excel to develop a decision model. Decision model parameters were determined using published literature, local hospital data, expert opinion, and chart review. Our cost-minimization analysis aggregated costs related to pharmaceuticals, laboratory testing, and hematologist fees. Our cost-effectiveness analysis also included costs related to health outcomes. Results: Our cost-minimization analysis found apixaban to be the least costly intervention at three months ($609.28). At six months and one year LMWH overlapped with VKA was the least costly intervention ($896.08 and $1,193.88, respectively). With respect to cost-effectiveness, at three months apixaban was the dominant strategy. At six months, apixaban was cost-effective given a willingness-to-pay per QALY as low as $4,986.81. At one year, LMWH overlapped with VKA was cost-effective given a willingness-to-pay per QALY below $135,670.28. Probabilistic sensitivity analysis of our cost-effectiveness analysis found apixaban to be the dominant strategy compared to LMWH overlapped with VKA in 42.6% of iterations and 70.6% of iterations resulted in incremental cost-effectiveness ratio below $100,000 per QALY gained. Conclusions: Our findings suggest apixaban is the least costly and most cost-effective strategy for short-term anticoagulant treatment for VTE but favor LMWH overlapped with VKA for long-term treatment. Disclosures No relevant conflicts of interest to declare.

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Real-World Adherence and Persistence to Direct Oral Anticoagulants in Patients With Atrial Fibrillation

Circulation Cardiovascular Quality and Outcomes ◽

10.1161/circoutcomes.119.005969 ◽

2020 ◽

Vol 13 (3) ◽

Cited By ~ 5

Author(s):

Aya F. Ozaki ◽

Austin S. Choi ◽

Quan T. Le ◽

Dennis T. Ko ◽

Janet K. Han ◽

...

Keyword(s):

Atrial Fibrillation ◽

Clinical Outcomes ◽

Real World ◽

Observational Studies ◽

Vitamin K Antagonists ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Medication Possession Ratio ◽

Good Adherence ◽

Proportion Of Days Covered

Background: Stroke reduction with direct oral anticoagulants (DOACs) in atrial fibrillation (AF) is dependent on adherence and persistence in the real-world setting. Individual study estimates of DOAC adherence/persistence rates have been discordant. Our aims were to characterize real-world observational evidence for DOAC adherence/persistence and evaluate associated clinical outcomes in patients with AF. Methods and Results: PubMed, EMBASE, and CINAHL were searched from inception to June 2018. Observational studies that reported real-world DOAC adherence/persistence in patients with AF were included. Study quality was assessed using the Newcastle-Ottawa Scale. Meta-analyses for pooled estimates were performed using DerSimonian and Laird random-effects models. Outcomes included DOAC mean proportion of days covered or medication possession ratio, proportion of good adherence (proportion of days covered/medication possession ratio ≥80%), persistence, DOAC versus vitamin K antagonists persistence, and clinical outcomes associated with nonadherence/nonpersistence. Forty-eight observational studies with 594 784 unique patients with AF (59% male; mean age 71 years) were included. The overall pooled mean proportion of days covered/medication possession ratio was 77% (95% CI, 75%–80%), proportion of patients with good adherence was 66% (95% CI, 63%–70%), and proportion persistent was 69% (95% CI, 65%–72%). The pooled proportion of patients with good adherence was 71% (95% CI, 64%–78%) for apixaban, 60% (95% CI, 52%–68%) for dabigatran, and 70% (95% CI, 64%–75%) for rivaroxaban. Similar patterns were found for pooled persistence by agent. The pooled persistence was higher with DOACs than vitamin K antagonists (odds ratio, 1.44 [95% CI, 1.12–.86]). DOAC nonadherence was associated with an increased risk of stroke (hazard ratio, 1.39 [95% CI, 1.06–1.81]). Conclusions: Suboptimal adherence and persistence to DOACs was common in patients with AF, with 1 in 3 patients adhering to their DOAC <80% of the time, which was associated with poor clinical outcomes in nonadherent patients. Although it is convenient that DOACs do not require laboratory monitoring, greater effort in monitoring for and interventions to prevent nonadherence may be necessary to optimize stroke prevention. Increased clinician awareness of DOAC nonadherence may help identify at-risk patients.

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Direct oral anticoagulants versus vitamin K antagonists in real-world patients with nonvalvular atrial fibrillation. The FANTASIIA study

Revista Española de Cardiología (English Edition) ◽

10.1016/j.rec.2019.02.021 ◽

2020 ◽

Vol 73 (1) ◽

pp. 14-20

Author(s):

Manuel Anguita Sánchez ◽

Vicente Bertomeu Martínez ◽

Martín Ruiz Ortiz ◽

Ángel Cequier Fillat ◽

Inmaculada Roldán Rabadán ◽

...

Keyword(s):

Atrial Fibrillation ◽

Vitamin K ◽

Real World ◽

Vitamin K Antagonists ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Nonvalvular Atrial Fibrillation

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Real-World Cost-Effectiveness Analysis of Gemcitabine and Cisplatin Compared to Docetaxel and Cisplatin Plus Fluorouracil Induction Chemotherapy in Locoregionally Advanced Nasopharyngeal Carcinoma

Frontiers in Oncology ◽

10.3389/fonc.2020.594756 ◽

2020 ◽

Vol 10 ◽

Author(s):

Jiangping Yang ◽

Jiaqi Han ◽

Jinlan He ◽

Baofeng Duan ◽

Qiheng Gou ◽

...

Keyword(s):

Sensitivity Analysis ◽

Cost Effectiveness ◽

Nasopharyngeal Carcinoma ◽

Incremental Cost ◽

Real World ◽

Cost Effective ◽

Model Parameters ◽

The Cost ◽

The Impact ◽

Gemcitabine And Cisplatin

BackgroundAddition of gemcitabine and cisplatin (GP) or docetaxel and cisplatin plus fluorouracil (TPF) to concurrent chemoradiotherapy (CCRT) signiﬁcantly improved survival in locoregionally advanced nasopharyngeal carcinoma (NPC). However, an economic evaluation of these regimens remains unknown. The purpose of this study is to compare the cost-effectiveness of GP versus TPF regimen in the treatment of locoregionally advanced NPC in China.Materials and methodsA comprehensive Markov model was developed to evaluate the health and economic outcomes of GP versus TPF regimen for patients with locoregionally advanced NPC. Baseline and clinical outcome were derived from 158 patients with newly diagnosed stage III-IVA NPC between 2010 and 2015. We evaluated the quality-adjusted life-years (QALYs), costs, and incremental cost-effectiveness ratios (ICERs) from the perspective of the Chinese healthcare system. One-way sensitive analysis explored the impact of uncertainty in key model parameters on results, and probabilistic uncertainty was assessed through a Monte Carlo probabilistic sensitivity analysis.ResultsGP regimen provided an additional 0.42 QALYs with incremental cost of $3,821.99, resulting in an ICER of $9,099.98 per QALY versus TPF regimen at the real-world setting. One-way sensitivity analysis found that the results were most sensitive to the cost and proportion of receiving subsequent treatment in two groups. The probability that GP regimen being cost-effective compared with TPF regimen was 86.9% at a willingness-to-pay (WTP) of $31,008.16 per QALY.ConclusionUsing real-world data, GP regimen was demonstrated a cost-effective alternative to TFP regimen for patients with locoregionally advanced NPC in China. It provides valuable evidence for clinicians when making treatment decisions to improve the cost-effectiveness of treatment.

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The use of mathematical model approach to select direct oral anticoagulants in patients with atrial fibrillation

European Heart Journal ◽

10.1093/ehjci/ehaa946.3374 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

S.V Malchikova ◽

N.S Maksimchuk-Kolobova ◽

M.V Kazakovtseva

Keyword(s):

Atrial Fibrillation ◽

Mathematical Model ◽

Cost Effectiveness ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Economic Effect ◽

Economic Effectiveness ◽

Stroke Treatment ◽

Life Years ◽

The Cost

Abstract Purpose To evaluate the clinical and economic effectiveness of direct oral anticoagulants (DOAC) - dabigatran/D, rivaroxaban/R, apixaban/A compared with warfarin/W in the treatment of atrial fibrillation (AF). Methods The mathematical model (MM) was used (decision-tree building- DTB) to assess the clinical and economic effectiveness of the DOAC use in comparison with W in the AF treatment. MM was based on the results of basic clinical trials on the use of D (RE-LY); R (ROCKET) and A (ARISTOTLE). MM was carried out on a time horizon of 5 years from the perspective of the healthcare system (HS). The method of cost-effectiveness analysis CER. CER = DC/Ef, CER is the cost-effectiveness balance of the alternative, DC is direct costs, Ef is the number of adjusted life years (ALY) and adjusted life years without complications (ALYC). Budget Impact Analysis. BIA = S (1) − S (2), BIA is the result of the analysis of “impact on the budget”, in monetary terms; S (l) – the total economic effect of the use of one drug, in monetary terms; S (2) – the total economic effect of the use of another drug, in monetary terms. Analysis of “lose opportunities”. MOA = ΔS/Costmin, MOA is the result of the analysis of “lose opportunities”, ΔS is the difference in the total economic effects of the two compared drugs, Costmin is the cost of using the lowest cost drugs. Results The MM showed that as a result of pair-wise comparison the DOAC and W, the greatest DC were in group of treatment with the W. The total costs when using D were 10.3% less and amounted to 4129711 against 4605164 rub. per 100 patients. The cost of using R is 5.2% less (4887744 against 5156589); using A by 10.9% (3946528 against 4433820). The greatest difference was due to the different costs of adverse drug reaction treatment (30–38% in the cost structure). In the D group, this cost component was less than the W -by 22.0%, in the R – by 10.9%, in the A – by 36.8%. Costs associated with ischemic stroke treatment were less then 28.1% in the D group. The strategy of using DOAK compared with W allows to provide a greater number of ALY and ALYC – 4, 34 and 4.3 when comparing D and W, 4.3 and 4.25 when R and W; and 4.25 and 4.2 – A and W. ALYC respectively – 3.92 and 3.79; 3.51 and 3.6; 3.9 and 3.74. The cost of ALY is 9516.65 against 10706.45 rub; 11,374.34/12123.81; 9,295.19/10547.31. The cost of ALYC respectively: 10,534.98 against 12150.83 rub.; 13,925.20/14733.11 and 10119.3/11855.13. The use of DOAK allows to save significant public funds, and the savings saved allow to treat the patients in addition by modern drugs. Savings up to 12% in 5 years, while up to 33 patients out of 1000 can be treated additionally. Conclusion DC resulting from the prevention of thromboembolic complications when using DOAC in comparison with W can be reduced by 28.1%, hemorrhagic complications by 36.8%. DOAC can save a greater number of ALY and ALYC at a lower cost. Funding Acknowledgement Type of funding source: None

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The Study of Cost-Effectiveness of Rivaroxaban versus Warfarin in Patients with Atrial Fibrillation Who Developed Ischemic Stroke

Stroke Research and Treatment ◽

10.1155/2021/5534873 ◽

2021 ◽

Vol 2021 ◽

pp. 1-8

Author(s):

Neda Jaberi ◽

Zahra Kavosi ◽

Etrat Hooshmandi ◽

Nasrin Moradi ◽

Khosro Keshavarz ◽

...

Keyword(s):

Atrial Fibrillation ◽

Sensitivity Analysis ◽

Ischemic Stroke ◽

Cost Effectiveness ◽

Cost Effective ◽

Evaluation Study ◽

Intermediate Outcomes ◽

The Social ◽

The One ◽

The Cost

Introduction. Rivaroxaban is a new anticoagulant providing benefits for the treatment of patients with atrial fibrillation (AF). This study is aimed at evaluating the cost-effectiveness of rivaroxaban compared to warfarin in patients with AF. Method. This economic evaluation study was conducted among 144 selected nonrandomly patients who were treated with rivaroxaban or warfarin and suffered from AF leading to stroke, in the stroke ward of Shiraz Nemazee Hospital in 2019. The final and clinical (intermediate) outcomes were QALYs and no bleeding and prevention of ischemic stroke, respectively. The study was performed from the social perspective, and a deterministic one-way sensitivity analysis was conducted to identify the effects of uncertainty. The analysis of the collected data was carried out using SPSS18 and TreeAge software. Results. Patients who received rivaroxaban had lower costs ($ 25275 vs. $ 26554) and higher QALYs (0.5 vs. 0.33) compared to those taking warfarin. Bleeding and stroke occurred in (9 vs. 40) and (1 vs. 3) patients in the rivaroxaban and warfarin groups, respectively, and there was a significant decrease in the incidence of bleeding in the rivaroxaban group (81.9% vs 44.4%). Thus, rivaroxaban in all the outcomes was cheaper and more effective than warfarin. The one-way sensitivity analysis confirmed the robustness of the results. Conclusions. Considering the incremental cost-effectiveness ratio, rivaroxaban is more cost-effective and can be a dominant alternative. Therefore, it is suggested to use rivaroxaban as the first priority in AF patients because rivaroxaban reduces costs and increases clinical outcomes compared with warfarin.

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