Non-warfarin oral anticoagulant copayments and adherence in atrial fibrillation: A population-based cohort study.

BACKGROUND: In patients with atrial fibrillation, incomplete adherence to anticoagulants increases risk of stroke. Non-warfarin oral anticoagulants (NOACs) are expensive; we evaluated whether higher copayments are associated with lower NOAC adherence. METHODS: Using a national claims database of commercially-insured patients, we performed a cohort study of patients with atrial fibrillation who newly initiated a NOAC from 2012 to 2018. Patients were stratified into low (<$35), medium ($35-$59), or high (≥$60) copayments and propensity-score weighted based on demographics, insurance characteristics, comorbidities, prior health care utilization, calendar year, and the NOAC received. Follow-up was 1 year, with censoring for switching to a different anticoagulant, undergoing an ablation procedure, disenrolling from the insurance plan, or death. The primary outcome was adherence, measured by proportion of days covered (PDC). Secondary outcomes included NOAC discontinuation (no refill for 30 days after the end of NOAC supply) and switching anticoagulants. We compared PDC using a Kruskal-Wallis test and rates of discontinuation and switching using Cox proportional hazards models. RESULTS: After weighting patients across the 3 copayment groups, the effective sample size was 17,558 patients, with balance across 50 clinical and demographic covariates (standardized differences <0.1). Mean age was 62 years, 29% of patients were female, and apixaban (43%), and rivaroxaban (38%) were the most common NOACs. Higher copayments were associated with lower adherence (P < .001), with a PDC of 0.82 (Interquartile range [IQR] 0.36-0.98) among those with high copayments, 0.85 (IQR 0.41-0.98) among those with medium copayments, and 0.88 (IQR 0.41-0.99) among those with low copayments. Compared to patients with low copayments, patients with high copayments had higher rates of discontinuation (hazard ratio [HR] 1.13, 95% confidence interval [CI] 1.08-1.19; P < .001). CONCLUSIONS: Among atrial fibrillation patients newly initiating NOACs, higher copayments in commercial insurance were associated with lower adherence and higher rates of discontinuation in the first year. Policies to lower or limit cost-sharing of important medications may lead to improved adherence and better outcomes among patients receiving NOACs.

Burden of oral anticoagulation in embolic stroke of undetermined source without atrial fibrillation.

OBJECTIVE: Prevention of recurrent stroke in patients with embolic stroke of undetermined source (ESUS) is challenging. The advent of safer anticoagulation in the form of direct oral anticoagulants (DOACs) has prompted exploration of prophylactic anticoagulation for all ESUS patients, rather than anticoagulating just those with documented atrial fibrillation (AF). However, recent trials have failed to demonstrate a clinical benefit, while observing increased bleeding. We modeled the economic impact of anticoagulating ESUS patients without documented AF across multiple geographies. METHODS: CRYSTAL-AF trial data were used to assess ischaemic stroke event rates in ESUS patients confirmed AF-free after long-term monitoring. Anticipated bleeding event rates (including both minor and major bleeds) with aspirin, dabigatran 150 mg, and rivaroxaban 20 mg were sourced from published meta-analyses, whilst a 30% ischaemic stroke reduction for both DOACs was assumed. Cost data for clinical events and pharmaceuticals were collected from the local payer perspective. RESULTS: Compared with aspirin, dabigatran and rivaroxaban resulted in 17.9 and 29.9 additional bleeding events per 100 patients over a patient's lifetime, respectively. Despite incorporating into our model the proposed 30% reduction in ischaemic stroke risk, both DOACs were cost-additive over patient lifetime, as the costs of bleeding events and pharmaceuticals outweighed cost savings associated with the reduction in ischaemic strokes. DOACs added £5953-£7018 per patient (UK), €6683-€7368 (Netherlands), €4933-€9378 (Spain), AUD$5353-6539 (Australia) and $26,768-$32,259 (US) of payer cost depending on the agent prescribed. Additionally, in the U.S. patient pharmacy co-payments ranged from $2468-$12,844 depending on agent and patient plan. In all settings, cost-savings could not be demonstrated even when the modelling assumed 100% protection from recurrent ischaemic strokes, due to the very low underlying risk of recurrent ischaemic stroke in this population (1.27 per 100 patient-years). CONCLUSIONS: Anticoagulation of non-AF patients may cause excess bleeds and add substantial costs for uncertain benefits, suggesting a personalised approach to anticoagulation in ESUS patients.

[Comparative clinical and economic evaluation of pharmacogenetic testing application for dabigatran in patients with atrial fibrillation].

AIM: To evaluate the clinical and economic feasibility of pharmacogenetic testing (PGT) for dabigataran etexilate administration in the treatment of atrial fibrillation (AF) without valve in comparison with tactics without pharmacogenetic testing. MATERIALS AND METHODS: The pharmacoeconomic model was done using generalized data from published clinical, epidemiological and clinical - economic studies. RESULTS AND DISCUSSION: Application of PGT on the carrier of allelic variant rs2244613 of CES1 gene for adjustment of dabigatrane etexilate dosage in patients with non - valve AF may be more cost - effective strategy for prevention of thromboembolic complications in patients with non - valve AF. Thus, due to the decrease in the number of undesirable drug reactions in the form of minor and major bleedings, the difference in treatment costs in the group with PGT compared to the group with standard pharmacotherapy tactics per 100 patients was 11 827.65 rubles. The expected cost per patient per year for standard treatment was 36 051.35 rubles, while in the group with PGT it was 35 933.07 rubles. The difference was 1182.76 rubles in favor of the pharmacogenetic approach Conclusion. A PGT approach to correct dabigatrane dosage can reduce the cost of pharmacotherapy by reducing the risk of adverse reactions of minor and major bleeding.

Anticoagulation Therapy for Atrial Fibrillation in Patients With Alzheimer's Disease.

Background and Purpose- Direct oral anticoagulants (DOACs) are safer, at least equally efficacious, and cost-effective compared to warfarin for stroke prevention in atrial fibrillation (AF) but they remain underused, particularly in demented patients. We estimated the cost-effectiveness of DOACs compared with warfarin in patients with AF and Alzheimer's disease (AD). Methods- We constructed a microsimulation model to estimate the lifetime costs, quality-adjusted life-years (QALYs), and cost-effectiveness of anticoagulation therapy (adjusted-dose warfarin and various DOACs) in 70-year-old patients with AF and AD from a US societal perspective. We stratified patient cohorts based on stage of AD and care setting. Model parameters were estimated from secondary sources. Health benefits were measured in the number of acute health events, life-years, and QALYs gained. We classified alternatives as cost-effective using a willingness-to-pay threshold of $100 000 per QALY gained. Results- For patients with AF and AD, compared with warfarin, DOACs increase costs but also increase QALYs by reducing the risk of stroke. For mild-AD patients living in the community, edoxaban increased lifetime costs by $6603 and increased QALYs by 0.076 compared to warfarin, yielding an incremental cost-effectiveness ratio of $86 882/QALY gained. Even though DOACs increased QALYs compared with warfarin for all patient groups (ranging from 0.019 to 0.085 additional QALYs), no DOAC treatment alternative had an incremental cost-effectiveness ratio <$150 000/QALY gained for patients with moderate to severe AD. For patients living in a long-term care facility with mild AD, the DOAC with the lowest incremental cost-effectiveness ratio (rivaroxaban) costs $150 169 per QALY gained; for patients with more severe AD, the incremental cost-effectiveness ratios were higher. Conclusions- For patients with AF and mild AD living in the community, edoxaban is cost-effective compared with warfarin. Even though patients with moderate and severe AD living in the community and patients with any stage of AD living in a long-term care setting may obtain positive clinical benefits from anticoagulation treatment, DOACs are not cost-effective compared with warfarin for these populations. Compared to aspirin, no oral anticoagulation (warfarin or any DOAC) is cost effective in patients with AF and AD.

Health Care Costs and Utilization of Dabigatran Compared With Warfarin for Secondary Stroke Prevention in Patients With Nonvalvular Atrial Fibrillation: A Retrospective Population Study.

BACKGROUND: It remains unclear whether the use of new oral anticoagulants, compared with warfarin, is economically beneficial in Asian countries. OBJECTIVE: The objective of this study is to compare the health care costs and utilization between dabigatran and warfarin in a real-world nonvalvular atrial fibrillation (NVAF) population. RESEARCH DESIGN: Data were obtained from the Taiwan National Health Insurance Database, and patients with an NVAF diagnosis between June 1, 2012, and May 31, 2014, were identified using the International Classification of Diseases, Ninth Revision code of 427.31. The patients in the dabigatran cohort were matched 1:2 to those in the warfarin cohort by sex, age, residential region, and a propensity score that incorporated a major bleeding history, CHADS2 score, and Charlson Comorbidity Index. The all-cause health care utilization and associated costs of the 2 treatment groups were compared at 3 and 12 months. RESULTS: A total of 1149 patients taking dabigatran were identified and matched with 2298 warfarin users. During the 3-month observation period, the likelihood of having at least 1 hospitalization among dabigatran users was significantly lower than that of warfarin users (odds ratio=0.78; P=0.001). Patients in the dabigatran group incurred lower mean emergency department costs ($2383.1 vs. $3033.6), mean ischemic stroke-related hospitalization costs ($8869.5 vs. $13,990.5), and mean all-cause hospitalization costs ($32,402.2 vs. $50,669.9) at 3 months. However, both the mean and median outpatient costs of warfarin users were consistently lower than those of dabigatran users ($17,161.2 vs. $24,931.4 and $10,509.0 vs. $20,671.5, respectively). Similar trends were observed at 12 months, except that the 2 groups had comparable total health care costs. CONCLUSIONS: The use of dabigatran is associated with lower emergency department and all-cause hospitalization costs but greater outpatient costs in a real-world, NVAF patient population compared with warfarin.

Target Population of Non-deferrable Surgery and Uncontrolled Severe Bleeding Related to Dabigatran.

PURPOSE: This observational study was aimed to identify patients who experienced non-deferrable surgery and/or uncontrolled severe bleeding following dabigatran administration and then are potentially eligible to the use of the specific antidote idarucizumab in a real-world setting. METHODS: From the big Italian real-world database ARCO, a cohort of adult patients treated with dabigatran and hospitalized due to diagnoses attributable to urgent interventions and/or major bleeding was selected in 2014. Baseline characteristics and all-cause hospitalizations, specialist/diagnostic outpatient services, and healthcare costs over the 1-year follow-up were described. RESULTS: Out of 16,756,843 Italian citizens, 271,540 (1.9%) were prescribed with oral anticoagulants, and specifically, 17,450 with dabigatran. Patients identified to be hospitalized for non-deferrable surgery (n = 106) and/or uncontrolled severe bleeding (n = 190) following dabigatran use were 289 (1.7%) [mean age (± SD) 79 ± 7, 50% of female sex]. On average, patients stayed in hospital 13.7 and 17.0 days, respectively. The per patient and per year cost to the Italian National Health System was on average 19,708€ (specifically 1487€ for drugs, of which 311€ for dabigatran, 17,353€ for all-cause hospitalizations, and 869€ for outpatient care), about four times more than the mean healthcare integrated cost of a single patient treated with dabigatran (4775€). CONCLUSIONS: This analysis of the ARCO database reliably describes the population potentially eligible to the dabigatran reversal agent, idarucizumab. These data may be useful for Healthcare Decision Makers to organize, define, and improve present and future emergency healthcare, mainly as starting point for cost-effectiveness analyses of new reversal agents.

THE GAP BETWEEN ECONOMIC EVALUATIONS AND CLINICAL PRACTICE: A SYSTEMATIC REVIEW OF ECONOMIC EVALUATIONS ON DABIGATRAN FOR ATRIAL FIBRILLATION.

OBJECTIVES: As model-based economic evaluations (MBEEs) are widely used to make decisions in the context of policy, it is imperative that they represent clinical practice. Here, we assess the relevance of MBEEs on dabigatran for the prevention of stroke in patients with atrial fibrillation (AF). METHODS: We performed a systematic review on the basis of a developed questionnaire, tailored to oral anticoagulation in patients with AF. Included studies had a full body text in English, compared dabigatran with a vitamin K antagonist, were not dedicated to one or more subgroup(s), and yielded an incremental cost-effectiveness ratio. The relevance of all MBEEs was assessed on the basis of ten context-independent factors, which encompassed clinical outcomes and treatment duration. The MBEEs performed for the United States were assessed on the basis of seventeen context-dependent factors, which were related to the country's target population and clinical environment. RESULTS: The search yielded twenty-nine MBEEs, of which six were performed for the United States. On average, 54 percent of the context-independent factors were included per study, and 37 percent of the seventeen context-dependent factors in the U.S. STUDIES: The share of relevant factors per study did not increase over time. CONCLUSIONS: MBEEs on dabigatran leave out several relevant factors, limiting their usefulness to decision makers. We strongly urge health economic researchers to improve the relevance of their MBEEs by including context-independent relevance factors, and modeling context-dependent factors befitting the decision context concerned.

Healthcare utilization and costs for patients initiating Dabigatran or Warfarin.

BACKGROUND: Novel oral anticoagulants (NOAC) such as dabigatran, when compared to warfarin, have been shown to potentially reduce the risk of stroke in patients with non-valvular atrial fibrillation (NVAF) together with lower healthcare resource utilization (HCRU) and similar total costs. This study expands on previous work by comparing HCRU and costs for patients newly diagnosed with NVAF and newly initiated on dabigatran or warfarin, and is the first study specifically in a Medicare population. METHODS: A retrospective matched-cohort study was conducted using data from administrative health care claims during the study period 01/01/2010-12/31/2012. Cox regression analyses were used to compare all-cause risk of first hospitalizations and emergency room (ER) visits. Medical, pharmacy, and total costs per-patient-per-month (PPPM) were compared between dabigatran and warfarin users. RESULTS: A total of 1110 patients initiated on dabigatran were propensity score-matched with corresponding patients initiated on warfarin. The mean number of hospitalizations (0.92 vs. 1.13, P = 0.012), ER visits (1.32 vs. 1.56, P < 0.01), office visits (21.43 vs. 29.41; P < 0.01), and outpatient visits (10.86 vs. 22.02; P < 0.01) were lower among dabigatran compared to warfarin users. Patients initiated on dabigatran had significantly lower risk of first all-cause ER visits [hazard ratio (HR): 0.84, 95% confidence interval (CI): 0.73-0.98] compared to those initiated on warfarin. Adjusted mean pharmacy costs PPPM were significantly greater for dabigatran users ($510 vs. $250, P < 0.001); however, mean medical costs PPPM ($1912 vs. $1956, P = 0.55) and mean total costs PPPM ($2381 vs. $2183, P = 0.10) were not significantly different compared to warfarin users. CONCLUSIONS: Dabigatran users had significantly lower HCRU compared to warfarin users. In addition, dabigatran users had lower risk of all-cause ER visits. Despite higher pharmacy costs, the two cohorts did not differ significantly in medical or total all-cause costs.

A cost-utility analysis of dabigatran, enoxaparin, and usual care for venous thromboprophylaxis after hip or knee replacement surgery in Thailand.

To analyze the cost-utility of oral dabigatran etexilate, enoxaparin sodium injection, and no intervention for venous thromboembolism (VTE) prophylaxis after total hip or knee replacement (THR/TKR) surgery among Thai patients. A cost-utility analysis using a decision tree model was conducted using societal and healthcare payers' perspectives to simulate relevant costs and health outcomes covering a 3-month time horizon. Costs were adjusted to year 2014. The willingness-to-pay threshold of THB 160,000 (USD 4926) was used. One-way sensitivity and probabilistic sensitivity analyses using a Monte Carlo simulation were performed. Compared with no VTE prophylaxis, dabigatran and enoxaparin after THR and TKR surgery incurred higher costs and increased quality adjusted life years (QALYs). However, their incremental cost-effectiveness ratios were high above the willingness to pay. Compared with enoxaparin, dabigatran for THR/TKR lowered VTE complications but increased bleeding cases; dabigatran was cost-saving by reducing the costs [by THB 3809.96 (USD 117.30) for THR] and producing more QALYs gained (by 0.00013 for THR). Dabigatran (vs. enoxaparin) had a 98 % likelihood of being cost effective. Dabigatran is cost-saving compared to enoxaparin for VTE prophylaxis after THR or TKR under the Thai context. However, both medications are not cost-effective compared to no thromboprophylaxis.

[Use of a Delphi survey to assess the hospital economic impact of innovative products: The example of idarucizumab a dabigatran-specific reversal agent]. / Utilisation du questionnaire Delphi pour anticiper l'impact économique des innovations thérapeutiques à l'hôpital : application à l'idarucizumab, le nouvel agent de réversion spécifique au dabigatran.

OBJECTIVES: The economic impact of therapeutic innovations on the hospital patient management cannot be easily estimated. The objective of this study is to illustrate the use of a Delphi survey as a support tool to identify the changes following the use of idarucizumab in dabigatran-treated patients with uncontrolled/life-threatening bleeding or who required emergency surgery/urgent procedures. METHODS: The Delphi questionnaires have been administrated to 8 emergency physicians or anesthetists from 6 different hospital centers. Following the answers, an economic valorization has been carried out on every parameter on which a consensus was reached (at least 4 answers showing an identical trend). A mean management cost for each etiology with and without the use of idarucizumab has thus been identified. RESULTS: For gastro-intestinal and other life-threatening bleedings (excepted intracranial bleedings), the total management cost of the hospital stay was respectively 6058 € (-35%) and 6219 € (-34%) following the use of the reversal agent. The hospital management cost for intracranial bleeding is slightly increasing to 9790 € (+3%). The cost of a stay for emergency surgery decreases to 6962€ (-2%). CONCLUSIONS: This study shows a positive economic impact following the use of the dabigatran-specific reversal agent for patients with uncontrolled/life-threatening bleeding excepted in the case of intracranial bleeding. Moreover, it points out that a Delphi survey is an easy way to predict the hospital economic impact of a therapeutic innovation when no other evaluation is possible.

Cost-Effectiveness of Oral Anticoagulants for Ischemic Stroke Prophylaxis Among Nonvalvular Atrial Fibrillation Patients.

BACKGROUND AND PURPOSE: The objective of the study is to compare the cost-effectiveness of oral anticoagulants among atrial fibrillation patients at an increased stroke risk. METHODS: A Markov model was constructed to project the lifetime costs and quality-adjusted survival (QALYs) of oral anticoagulants using a private payer's perspective. The distribution of stroke risk (CHADS2 score: congestive heart failure, hypertension, advanced age, diabetes mellitus, stroke) and age of the modeled population was derived from a cohort of commercially insured patients with new-onset atrial fibrillation. Probabilities of treatment specific events were derived from published clinical trials. Event and downstream costs were determined from the cost of illness studies. Drug costs were obtained from 2015 National Average Drug Acquisition Cost data. RESULTS: In the base case analysis, warfarin was the least costly ($46 241; 95% CI, 44 499-47 874) and apixaban had the highest QALYs (9.38; 95% CI, 9.24-9.48 QALYs). Apixaban was found to be a cost-effective strategy over warfarin (incremental cost-effectiveness ratio=$25 816) and dominated other anticoagulants. Probabilistic sensitivity analysis showed that apixaban had at least a 61% chance of being the most cost-effective strategy at willingness to pay value of $100 000 per QALY. Among patients with CHADS2 ≥3, dabigatran was the dominant strategy. The model was sensitive to efficacy estimates of apixaban, dabigatran, and edoxaban and the cost of these drugs. CONCLUSIONS: All the newer oral anticoagulants compared were more effective than adjusted dosed warfarin. Our model showed that apixaban was the most effective anticoagulant in a general atrial fibrillation population and has an incremental cost-effectiveness ratio <$50 000/QALY. For those with higher stroke risk (CHADS2≥3), dabigatran was the most cost-effective treatment option.

Cost-effectiveness analysis of dabigatran and anticoagulation monitoring strategies of vitamin K antagonist.

BACKGROUND: Vitamin K antagonists are commonly used for the prevention of thromboembolic events. Patient self-monitoring of vitamin K antagonists has proved superior to usual care. Dabigatran has been shown, relative to warfarin, to reduce thromboembolic events without increasing bleeding. METHODS: We constructed a Markov model to compare vitamin K self-monitoring strategies to dabigatran including effectiveness and costs of monitoring and complications (thromboembolism and major bleeding). The model was used to project the incidence of these complications, life years, quality-adjusted life years, and health system costs with anticoagulant treatment throughout life. The analysis was conducted from the health system perspective and from the societal perspective. RESULTS: Low quality evidence suggests that self-monitoring is at least as effective as dabigatran for the outcomes of thrombosis, bleeding and death. Moderate quality evidence that patient self-monitoring is more effective than other forms of monitoring degree of anticoagulation with vitamin K antagonists, reducing the relative risk of thromboembolism by 41% and death by 34%. The cost per quality adjusted year gained relative to other warfarin monitoring strategies is well below 30,000 € in the short term, and is a dominant alternative from the fourth year. In comparison with dabigatran, the lower annual cost and its equivalence in terms of effectiveness made self-monitoring the dominant option. These results were confirmed in the probabilistic sensitivity analysis. CONCLUSIONS: We have moderate quality evidence that self-monitoring of vitamin K antagonists is a cost-effective alternative compared with hospital and primary care monitoring, and low quality evidence, compared with dabigatran. Our analyses contrast with the available cost analysis of dabigatran and usual care of anticoagulated patients.

Cost-Effectiveness of Novel Oral Anticoagulants for Stroke Prevention in Non-Valvular Atrial Fibrillation.

Recently, novel oral anticoagulants (NOACs) have been approved for stroke prevention in patients with atrial fibrillation (AF). Although these agents overcome some disadvantages of warfarin, they are associated with increased costs. In this review, we will provide an overview of the cost-effectiveness of NOACs for stroke prevention in AF. Our comments and conclusions are limited to studies directly comparing all available NOACs within the same framework. The available cost-effectiveness analyses suggest that NOACs are cost-effective compared to warfarin, with apixaban likely being most favorable. However, significant limitations in these models are present and should be appreciated when interpreting their results.

The Cost Implications of Dabigatran in Patients with Myocardial Injury After Non-Cardiac Surgery.

BACKGROUND: The Management of Myocardial Injury after Non-Cardiac Surgery (MANAGE) trial demonstrated that dabigatran 110 mg twice daily was more effective than placebo in preventing the primary composite outcome of vascular mortality, non-fatal myocardial infarction, non-hemorrhagic stroke, peripheral arterial thrombosis, amputation and symptomatic venous thromboembolism in patients with myocardial injury after non-cardiac surgery (MINS). The cost implications of dabigatran for this population are unknown but are important given the significant clinical implications. METHODS: Hospitalized events, procedures, and study and non-study medications were documented. We applied Canadian unit costs to healthcare resources consumed for all patients in the trial, and calculated the average cost per patient in Canadian dollars for the duration of the study (median follow-up of 16 months). A sensitivity analysis was performed using only Canadian patients, and subgroup analyses were also conducted. RESULTS: The total study cost for the dabigatran group was $9985 per patient, compared with $10,082 for placebo, a difference of - $97 (95% confidence interval [CI] - $2128 to $3672). Savings arising from fewer clinical events and procedures in the dabigatran 110 mg twice-daily group were enough to offset the cost of the study drug. In Canadian patients, the difference was $250 (95% CI -$2848 to $4840). Both differences were considered cost neutral. Dabigatran 110 mg twice daily was cost saving or cost neutral in many subgroups that were considered. CONCLUSION: Dabigatran 110 mg twice daily was cost neutral for patients in the MANAGE trial. Our cost findings support the use of dabigatran 110 mg twice daily in patients with MINS. TRIAL REGISTRATION: ClinicalTrials.gov identifier number NCT01661101.

Cost-effectiveness of Dabigatran Compared With Rivaroxaban for Prevention of Stroke and Systemic Embolism in Patients With Atrial Fibrillation in China.

PURPOSE: In China, dabigatran and rivaroxaban are the only approved non-vitamin K antagonist oral anticoagulants for the treatment of atrial fibrillation (AF). The goal of this article was to assess the cost-effectiveness of dabigatran versus rivaroxaban for the prevention of stroke and systemic embolism in Chinese patients with AF from the perspective of the Chinese health care system. METHODS: A Markov model was constructed to estimate the cost-effectiveness of dabigatran versus rivaroxaban. Clinical events were modeled for a lifetime horizon, based on clinical efficacy data from indirect treatment comparisons. The weighted average of the most recent prices of these 2 drugs was used as the drug acquisition cost. Other costs, including follow-up costs and event costs, were collected by using a survey from a panel of local experts. Utility inputs (health state utilities, clinical event disutilities, and event history utility) were obtained from published literature. Sensitivity analyses that included scenario analyses and a probabilistic sensitivity analysis were conducted to examine the robustness of the economic model. FINDINGS: Over a lifetime, patients treated with dabigatran experienced fewer ischemic strokes (2.14 dabigatran vs 2.61 rivaroxaban) and fewer intracranial hemorrhage (0.48 vs 0.94) per 100 patient-years. In the base case analysis, dabigatran had an incremental cost of ¥28,128 but with higher life years (10.38 vs 10.14) and quality-adjusted life years (QALYs) (7.95 vs 7.70). The resulting incremental cost-effectiveness ratio of ¥112,910 per QALY gained and net monetary benefit of ¥12,214 versus rivaroxaban showed that dabigatran was a cost-effective alternative to rivaroxaban. Extensive sensitivity analyses indicated that the results were robust over a wide range of inputs. The probabilistic sensitivity analysis indicated that dabigatran was cost-effective in 84.2% of the 10,000 Monte Carlo simulations compared with rivaroxaban. IMPLICATIONS: Dabigatran reduced the occurrence of clinical events and increased QALYs compared with rivaroxaban. The use of dabigatran for the prevention of stroke and systemic embolism is a cost-effective option compared with rivaroxaban among patients with AF in China.

Predicting Cost-Effectiveness of Generic vs. Brand Dabigatran Using Pharmacometric Estimates Among Patients with Atrial Fibrillation in the United States.

Generic entry of newer anticoagulants is expected to decrease the costs of atrial fibrillation management. However, when making switches between brand and generic medications, bioequivalence concerns are possible. The objectives of this study were to predict and compare the lifetime cost-effectiveness of brand dabigatran with hypothetical future generics. Markov microsimulations were modified to predict the lifetime costs and quality-adjusted life years of patients on either brand or generic dabigatran from a US private payer perspective. Event rates for generics were predicted using previously developed pharmacokinetic-pharmacodynamic models. The analyses showed that generic dabigatran with lower-than-brand systemic exposure were dominant. Meanwhile, generic dabigatran with extremely high systemic exposure was not cost-effective compared with the brand reference. Cost-effectiveness of generic medications cannot always be assumed as shown in this example. Combined use of pharmacometric and pharmacoeconomic models can assist in decision making between brand and generic pharmacotherapies.

Cost-effectiveness of antithrombotic agents for atrial fibrillation in older adults at risk for falls: a mathematical modelling study.

BACKGROUND: Antithrombotic drugs decrease stroke risk in patients with atrial fibrillation, but they increase bleeding risk, particularly in older adults at high risk for falls. We aimed to determine the most cost-effective antithrombotic therapy in older adults with atrial fibrillation who are at high risk for falls. METHODS: We conducted a mathematical modelling study from July 2019 to March 2020 based on the Ontario, Canada, health care system. We derived the base-case age, sex and fall risk distribution from a published cohort of older adults at risk for falls, and the bleeding and stroke risk parameters from an atrial fibrillation trial population. Using a probabilistic microsimulation Markov decision model, we calculated quality-adjusted life years (QALYs), total cost and incremental cost-effectiveness ratios (ICERs) for each of acetylsalicylic acid (ASA), warfarin, apixaban, dabigatran, rivaroxaban and edoxaban. Cost data were adjusted for inflation to 2018 values. The analysis used the Ontario public payer perspective with a lifetime horizon. RESULTS: In our model, the most cost-effective antithrombotic therapy for atrial fibrillation in older patients at risk for falls was apixaban, with an ICER of $8517 per QALY gained (5.86 QALYs at $92 056) over ASA. It was a dominant strategy over warfarin and the other antithrombotic agents. There was moderate uncertainty in cost-effectiveness ranking, with apixaban as the preferred choice in 66% of model iterations (given willingness to pay of $50 000 per QALY gained); edoxaban, 30 mg, was preferred in 31% of iterations. Sensitivity analysis across ranges of age, bleeding risk and fall risk still favoured apixaban over the other medications. INTERPRETATION: From a public payer perspective, apixaban is the most cost-effective antithrombotic agent in older adults at high risk for falls. Health care funders should implement strategies to encourage use of the most cost-effective medication in this population.

Pharmaceutical industry funding of events for healthcare professionals on non-vitamin K oral anticoagulants in Australia: an observational study.

OBJECTIVES: To describe the nature, frequency and content of non-vitamin K oral anticoagulant (NOAC)-related events for healthcare professionals sponsored by the manufacturers of the NOACs in Australia. A secondary objective is to compare these data to the rate of dispensing of the NOACs in Australia. DESIGN AND SETTING: This cross-sectional study examined consolidated data from publicly available Australian pharmaceutical industry transparency reports from October 2011 to September 2015 on NOAC-related educational events. Data from April 2011 to June 2016 on NOAC dispensing, subsidised under Australia's Pharmaceutical Benefits Scheme (PBS), were obtained from the Department of Health and the Department of Human Services. MAIN OUTCOME MEASURES: Characteristics of NOAC-related educational events including costs (in Australian dollars, $A), numbers of events, information on healthcare professional attendees and content of events; and NOAC dispensing rates. RESULTS: During the study period, there were 2797 NOAC-related events, costing manufacturers a total of $A10 578 745. Total expenditure for meals and beverages at all events was $A4 238 962. Events were predominantly attended by general practitioners (42%, 1174/2797), cardiologists (35%, 977/2797) and haematologists (23%, 635/2797). About 48% (1347/2797) of events were held in non-clinical settings, mainly restaurants, bars and cafes. Around 55% (1551/2797) of events consisted of either conferences, meetings or seminars. The analysis of the content presented at two events detected promotion of NOACs for unapproved indications, an emphasis on a favourable benefit/harm profile, and that all speakers had close ties with the manufacturers of the NOACs. Following PBS listings relevant to each NOAC, the numbers of events related to that NOAC and the prescribing of that NOAC increased. CONCLUSIONS: Our findings suggest that the substantial investment in NOAC-related events made by four pharmaceutical companies had a promotional purpose. Healthcare professionals should seek independent information on newly subsidised medicines from, for example, government agencies or drug bulletins.

Total costs of treating venous thromboembolism: implication of different cost perspectives in a Danish setting.

Aim: Optimal use of scarce resources is a focus in the healthcare sector, as resources devoted to health care are limited. Costs and health economic analyses can help guide decision-making concerning treatments. One important factor is the choice of cost perspective that can range from a focus on narrow drug budget costs to broader economic perspectives. In the case of treatment with oral anticoagulants in patients with venous thromboembolism (VTE), encompassing deep vein thrombosis and pulmonary embolism, the aim of this cost analysis was to illustrate the differences in costs when applying different cost perspectives.Methods: In a cost analysis, pairwise comparisons of average costs of 6 months standard treatment with either a low molecular weight heparin parenteral anticoagulant (LMWH) and a Vitamin K Antagonist (VKA) versus one of the non-vitamin K oral anticoagulants [NOACs; dabigatran etexilate, rivaroxaban, apixaban, and edoxaban) used in daily clinical practice in Denmark for VTE patients were carried out. Each analysis included the results from five different cost analyses with increasingly broader cost perspectives going from the narrowest "drug cost only" perspective to the broadest "societal" perspective.Results: Focusing on "drug costs only", LMWH/VKA was associated with the lowest costs compared to all NOACs. However, including the economic impact of preventing recurrent VTE and limit bleedings, apixaban and rivaroxaban resulted in slightly lower health care costs than LMWH/VKA. When applying the "societal perspective", the total costs saved with apixaban and rivaroxaban compared to LMWH/VKA further increased, with apixaban having the lowest total costs.Conclusions: The present study's case of oral anticoagulants in VTE treatment illustrated the importance of the cost perspective in the choice of therapy. If decision-making were based on drug costs only, instead of applying a health care sector or societal cost perspective, suboptimal decisions may be likely.

Comparison of all-cause, stroke, and bleed-specific healthcare resource utilization among patients with non-valvular atrial fibrillation (NVAF) and newly treated with dabigatran or warfarin.

BACKGROUND: We compared healthcare utilization outcomes and persistence among non-valvular atrial fibrillation (NVAF) patients newly treated with dabigatran or warfarin. METHODS: Using a nationwide, US administrative claims database, a retrospective matched-cohort of newly diagnosed NVAF patients (age≥18 years) treated with dabigatran or warfarin (propensity score matched 1:1) in 01/01/2011-12/31/2013 was evaluated. All-cause, stroke-, and bleed-specific per patient per month (PPPM) healthcare resource utilization (HCRU), incidence rate of hospitalization for stroke or bleed, 30-day readmission, and persistence were reported. RESULTS: In total, 18,890 dabigatran patients were matched to corresponding warfarin patients. Compared to warfarin users, dabigatran users PPPM had significantly fewer all-cause hospitalizations (0.04 vs 0.05), total outpatient visits (3.98 vs 5.87), and lower 30-day readmissions (14.5% vs 17.4%, all p < 0.001). Dabigatran users had lower incidence rate for stroke (0.65 vs 1.06) and bleed (1.69 vs 2.20), stroke (0.0006 vs 0.0011, p < 0.001) and bleed-specific hospitalizations (0.002 vs 0.003, p = 0.008), and stroke (0.03 vs 0.04, p < 0.001) and bleed-specific outpatient visits (0.07 vs 0.08, p = 0.018), and significantly lower non-persistence (62.1% vs 66.3%, p < 0.001). CONCLUSION: Among newly diagnosed newly treated NVAF patients, dabigatran users had significantly lower all-cause, stroke- and bleed-specific HCRU, lower risk of hospitalization for stroke or bleed events, lower 30-day readmissions, and higher persistence than warfarin users.