Pharmacogenetic guided versus standard warfarin dosing for routine clinical care with its pharmacoeconomic impact: a randomized controlled clinical trial.

BACKGROUND: Empirical use of pharmacogenetic test(PGT) is advocated for many drugs, and resource-rich setting hospitals are using the same commonly. The clinical translation of pharmacogenetic tests in terms of cost and clinical utility is yet to be examined in hospitals of low middle income countries (LMICs). AIM: The present study assessed the clinical utility of PGT by comparing the pharmacogenetically(PGT) guided- versus standard of care(SOC)- warfarin therapy, including the health economics of the two warfarin therapies. METHODS: An open-label, randomized, controlled clinical trial recruited warfarin-receiving patients in pharmacogenetically(PGT) guided- versus standard of care(SOC)- study arms. Pharmacogenetic analysis of CYP2C9*2(rs1799853), CYP2C9*3(rs1057910) and VKORC1(rs9923231) was performed for patients recruited to the PGT-guided arm. PT(Prothrombin Time)-INR(international normalized ratio) testing and dose titrations were allowed as per routine clinical practice. The primary endpoint was the percent time spent in the therapeutic INR range(TTR) during the 90-day observation period. Secondary endpoints were time to reach therapeutic INR(TRT), the proportion of adverse events, and economic comparison between two modes of therapy in a Markov model built for the commonest warfarin indication- atrial fibrillation. RESULTS: The study enrolled 168 patients, 84 in each arm. Per-protocol analysis showed a significantly high median time spent in therapeutic INR in the genotype-guided arm(42.85%; CI 21.4-66.75) as compared to the SOC arm(8.8%; CI 0-27.2)(p < 0.00001). The TRT was less in the PG-guided warfarin dosing group than the standard-of-care dosing warfarin group (17.85 vs. 33.92 days) (p = 0.002). Bleeding and thromboembolic events were similar in the two study groups. Lifetime expenditure was ₹1,26,830 in the PGT arm compared to ₹1,17,907 in the SOC arm. The QALY gain did not differ in the two groups(3.9 vs. 3.65). Compared to SOC, the incremental cost-utility ratio was ₹35,962 per QALY gain with PGT test opting. In deterministic and probabilistic sensitivity analysis, the base case results were found to be insensitive to the variation in model parameters. In the cost-effectiveness-acceptability curve analysis, a 90% probability of cost-effectiveness was reached at a willingness-to-pay(WTP) of ₹ 71,630 well below one time GDP threshold of WTP used. CONCLUSION: Clinical efficacy and the cost-effectiveness of the warfarin pharmacogenetic test suggest its routine use as a point of care investigation for patient care in LMICs.

Early experience of using regional citrate anticoagulation for continuous renal replacement therapy in critically ill patients in a resource-limited setting.

AIM: Despite the superiority of regional citrate anticoagulation (RCA) in continuous renal replacement therapy (CRRT), its application is limited in resource-limited settings. We aim to explore the cost and safety of RCA for CRRT in critically ill patients, compared to usual care. METHODS: This prospective observational study included patients requiring CRRT in a tertiary intensive care unit (ICU) from February 2022 to January 2023. They were classified to either the RCA or usual care groups based on the anticoagulation technique chosen by the treating physician, considering contraindications. The CRRT prescription follows the institutional protocol. All relevant data were obtained from the ICU CRRT-RCA charts and electronic medical records. A cost analysis was performed. RESULTS: A total of 54 patients (27 per group) were included, with no demographic differences. Sequential Organ Failure Assessment score and lactate levels were significantly higher in the usual care group. The number of filters used were comparable (p = .108). The median filter duration in the RCA group was numerically longer (35.00 [15.50-56.00] vs. 23.00 [17.00-29.00] h), but not statistically significant (p = .253). The duration of mechanical ventilation, vasopressor requirement, and mortality were similar, but the RCA group had a significantly longer ICU stay. The rate of adverse events was similar, with four severe metabolic alkalosis cases in the RCA group. The RCA group had higher total cost per patient per day (USD 611 vs. 408; p = .013). CONCLUSION: In this resource-limited setting, RCA for CRRT appeared safe and had clinically longer filter lifespan compared with usual care, albeit the increased cost.

Prophylactic anticoagulation after minimally invasive hysterectomy for endometrial cancer: a cost-effectiveness analysis.

OBJECTIVE: To determine our institutional rate of venous thromboembolism (VTE) following minimally invasive surgery for endometrial cancer and to perform a cost-effectiveness analysis of extended prophylactic anticoagulation after minimally invasive staging surgery for endometrial cancer. METHODS: All patients with newly diagnosed endometrial cancer who underwent minimally invasive staging surgery from January 1, 2017 to December 31, 2020 were identified retrospectively, and clinicopathologic and outcome data were obtained through chart review. Event probabilities and utility decrements were obtained through published clinical data and literature review. A decision model was created to compare 28 days of no post-operative pharmacologic prophylaxis, prophylactic enoxaparin, and prophylactic apixaban. Outcomes included no complications, deep vein thrombosis (DVT), pulmonary embolism, clinically relevant non-major bleeding, and major bleeding. We assumed a willingness-to-pay threshold of $100 000 per quality-adjusted life year (QALY) gained. RESULTS: Three of 844 patients (0.36%) had a VTE following minimally invasive staging surgery for endometrial cancer. In this model, no pharmacologic prophylaxis was less costly and more effective than prophylactic apixaban and prophylactic enoxaparin over all parameters examined. When all patients were assigned prophylaxis, prophylactic apixaban was both less costly and more effective than prophylactic enoxaparin. If the risk of DVT was ≥4.8%, prophylactic apixaban was favored over no pharmacologic prophylaxis. On Monte Carlo probabilistic sensitivity analysis for the base case scenario, no pharmacologic prophylaxis was favored in 41.1% of iterations at a willingness-to-pay threshold of $100 000 per QALY. CONCLUSIONS: In this cost-effectiveness model, no extended pharmacologic anticoagulation was superior to extended prophylactic enoxaparin and apixaban in clinically early-stage endometrial cancer patients undergoing minimally invasive surgery. This model supports use of prophylactic apixaban for 7 days post-operatively in select patients when the risk of DVT is 4.8% or higher.

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.

Global access to affordable direct oral anticoagulants.

Poor control of cardiovascular disease accounts for a substantial proportion of the disease burden in developing countries, but often essential anticoagulant medicines for preventing strokes and embolisms are not widely available. In 2019, direct oral anticoagulants were added to the World Health Organization's WHO Model list of essential medicines. The aims of this paper are to summarize the benefits of direct oral anticoagulants for patients with cardiovascular disease and to discuss ways of increasing their usage internationally. Although the cost of direct oral anticoagulants has provoked debate, the affordability of introducing these drugs into clinical practice could be increased by: price negotiation; pooled procurement; competitive tendering; the use of patent pools; and expanded use of generics. In 2017, only 14 of 137 countries that had adopted national essential medicines lists included a direct oral anticoagulant on their lists. This number could increase rapidly if problems with availability and affordability can be tackled. Once the types of patient likely to benefit from direct oral anticoagulants have been clearly defined in clinical practice guidelines, coverage can be more accurately determined and associated costs can be better managed. Government action is required to ensure that direct oral anticoagulants are covered by national budgets because the absence of reimbursement remains an impediment to achieving universal coverage. Tackling cardiovascular disease with the aid of direct oral anticoagulants is an essential component of efforts to achieve the World Health Organization's target of reducing premature deaths due to noncommunicable disease by 25% by 2025.

L'absence de lutte efficace contre les maladies cardiovasculaires contribue grandement à la charge de morbidité pesant sur les pays en développement. Pourtant, les anticoagulants essentiels permettant d'éviter les accidents vasculaires cérébraux et les embolies sont souvent difficiles à obtenir. En 2019, les anticoagulants oraux directs ont été ajoutés à la Liste modèle des médicaments essentiels publiée par l'Organisation mondiale de la Santé. Le présent document vise à résumer les avantages des anticoagulants oraux directs pour les patients souffrant d'une maladie cardiovasculaire, et à évoquer les moyens d'encourager leur utilisation au niveau international. Bien que le coût des anticoagulants oraux directs ait fait débat, intégrer ces médicaments dans la pratique clinique les rendrait plus abordables grâce à diverses méthodes: négociation des prix; achats groupés; appels d'offres concurrentiels; communautés de brevets; et recours accru aux alternatives génériques. En 2017, seulement 14 des 137 pays ayant adopté des listes nationales de médicaments essentiels y avaient inclus des anticoagulants oraux directs. Ce chiffre pourrait augmenter rapidement si les problèmes de disponibilité et d'accessibilité peuvent être résolus. Dès que les profils des patients susceptibles d'être traités par des anticoagulants oraux directs sont clairement établis dans les directives de pratique clinique, la couverture peut être définie avec plus de précision et les dépenses correspondantes, mieux gérées. Les gouvernements doivent s'assurer que ces médicaments sont bien pris en compte dans les budgets nationaux, car l'absence de remboursement demeure un obstacle à la couverture maladie universelle. La lutte contre les maladies cardiovasculaires à l'aide des anticoagulants oraux directs est un élément essentiel des efforts destinés à atteindre l'objectif de l'OMS: faire baisser de 25% d'ici 2025 les décès prématurés dus aux maladies non transmissibles de 25% d'ici 2025.

El mal control de las enfermedades cardiovasculares representa una proporción importante de la carga de enfermedades en los países en desarrollo, y a menudo los medicamentos anticoagulantes esenciales para prevenir los accidentes cerebrovasculares y las embolias no son fácilmente accesibles. En 2019, los anticoagulantes orales directos se añadieron a la lista modelo de medicamentos esenciales de la Organización Mundial de la Salud. Los objetivos del presente artículo son resumir los beneficios de los anticoagulantes orales directos para los pacientes con enfermedades cardiovasculares y discutir las formas de aumentar su uso a nivel internacional. Aunque el coste de los anticoagulantes orales directos ha suscitado debate, la asequibilidad de introducir estos medicamentos en la práctica clínica podría aumentarse al: negociar precios; hacer adquisiciones conjuntas; hacer licitaciones competitivas; utilizar consorcios de patentes; y ampliar el uso de genéricos. En 2017, solo 14 de los 137 países que habían adoptado listas nacionales de medicamentos esenciales incluían un anticoagulante oral directo en sus listas. Este número podría aumentar rápidamente si se pueden abordar los problemas de disponibilidad y asequibilidad. Cuando los tipos de pacientes que pueden beneficiarse de los anticoagulantes orales directos se hayan definido claramente en las directrices de la práctica clínica, la cobertura podrá determinarse con mayor precisión y los costes asociados podrán gestionarse mejor. Es necesario que los gobiernos actúen para garantizar que los anticoagulantes orales directos estén cubiertos por los presupuestos nacionales, ya que la ausencia de reembolso sigue siendo un impedimento para lograr la cobertura universal. La lucha contra las enfermedades cardiovasculares con la ayuda de los anticoagulantes orales directos es un componente esencial de los esfuerzos por alcanzar el objetivo de la OMS de reducir las muertes prematuras debidas a enfermedades no transmisibles en un 25 % para 2025.

Cost-effectiveness analysis of rivaroxaban plus aspirin versus aspirin alone in secondary prevention among patients with chronic cardiovascular diseases.

PURPOSE: This study aimed to investigate the cost-effectiveness of low-dose rivaroxaban plus aspirin versus aspirin alone for patients with stable cardiovascular diseases in the Taiwan setting. METHODS: We constructed a Markov model to project the lifetime direct medical costs and quality-adjusted life-years of both therapies. Transitional probabilities were derived from the COMPASS trial, and the costs and utilities were obtained from the Taiwan National Health Insurance Database and published studies. One-way, scenario, subgroup, and probabilistic sensitivity analyses were performed to assess the uncertainty. Incremental cost-effectiveness ratio was presented as the outcome. The threshold of willingness-to-pay was set at US$76,368 (3 times the gross domestic product per capita of Taiwan). All analyses were operated by TreeAge 2019 and Microsoft Excel. RESULTS: The incremental cost-effectiveness ratios of rivaroxaban plus aspirin versus aspirin alone in the patients with stable cardiovascular diseases, coronary artery diseases, and peripheral artery diseases were US$83,459, US$69,852 and -US$13,823 per quality-adjusted life-year gained, respectively. The probabilistic sensitivity analyses showed that the probabilities of cost-effectiveness for the regimen with rivaroxaban among those with cardiovascular diseases and coronary artery diseases were 44.1% and 65.3% at US$76,368. CONCLUSION: Low-dose rivaroxaban plus aspirin is less likely to be a cost-effective alternative to aspirin in secondary prevention for the patients with stable cardiovascular diseases; however, among these patients, the regimen may have pharmacoeconomic incentives for the group merely having chronic coronary artery diseases from the Taiwan national payer's perspective. The pharmacoeconomic incentives are influenced by the drug price, event treatment fees, and willingness-to-pay threshold.

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.

Cost-effectiveness of rivaroxaban versus warfarin in non-valvular atrial fibrillation patients with chronic kidney disease in China.

WHAT IS KNOWN AND OBJECTIVE: In non-valvular atrial fibrillation (NVAF) patients with chronic kidney disease (CKD), rivaroxaban was not inferior to warfarin in preventing stroke and systemic embolism. However, a comparative evaluation of the cost-effectiveness of rivaroxaban and warfarin therapies for NVAF patients at different renal function levels has not yet been reported, and this study aimed to estimate the cost-effectiveness of rivaroxaban compared with warfarin in Chinese NVAF patients with CKD. METHODS: A Markov model was constructed to estimate quality-adjusted life years (QALYs) and lifetime costs associated with the use of rivaroxaban relative to warfarin in patients with NVAF at different estimated glomerular filtration rate (eGFR) levels as follows: 30 to <50, 50 to <80 and ≥80 mL/min. Input parameters were sourced from the clinical literature. Probabilistic sensitivity analyses were performed to assess model uncertainty. RESULTS AND DISCUSSION: The incrementalQALYs with rivaroxaban was slightly increased by approximately 0.3 QALY as compared with that with warfarin in all the subgroups, resulting in an ICER of $9,736/QALY (eGFR, 30 to <50 mL/min), $9,758/QALY (50 to <80 mL/min) and $9,969/QALY (≥80 mL/min). The probabilistic sensitivity analysis suggested a chance of >80% that the ICER would be lower than the willingness-to-pay threshold of three times the GDP of China in 2019 in all the subgroups. Results were consistent even under the assumption of anticoagulant discontinuation after major bleeding events. The model was most sensitive to event-free-related utility and survival rates. WHAT IS NEW AND CONCLUSION: The existing evidence supports the cost-effectiveness of rivaroxaban therapy as an alternative anticoagulant to warfarin for patients with NVAF at different renal function levels.

Cost-effectiveness analysis of low-dose direct oral anticoagulant (DOAC) for the prevention of cancer-associated thrombosis in the United States.

BACKGROUND: Randomized controlled trials (RCTs) have demonstrated that low-dose direct oral anticoagulants (DOACs), including rivaroxaban and apixaban, may help reduce the incidence of cancer-associated venous thromboembolism (VTE). METHODS: A cost-utility analysis was performed from the health sector perspective using a Markov state-transition model in patients with cancer who are at intermediate-to-high risk for VTE. Transition probability, relative risk, cost, and utility inputs were obtained from a meta-analysis of the RCTs and relevant epidemiology studies. Differences in cost, quality-adjusted life-years (QALYs), and the incremental cost-effectiveness ratio (ICER) per patient were calculated over a lifetime horizon. One-way, probabilistic, and scenario sensitivity analyses were conducted. RESULTS: In patients with cancer at intermediate-to-high risk for VTE, treatment with low-dose DOAC thromboprophylaxis for 6 months, compared with placebo, was associated with 32 per 1000 fewer VTE and 11 per 1000 more major bleeding episodes over a lifetime. The incremental cost and QALY increases were $1445 and 0.12, respectively, with an ICER of $11,947 per QALY gained. Key drivers of ICER variations included the relative risks of VTE and bleeding as well as drug cost. This strategy was 94% cost effective at the threshold of $50,000 per QALY. The selection of patients with Khorana scores ≥3 yielded the greatest value, with an ICER of $5794 per QALY gained. CONCLUSIONS: Low-dose DOAC thromboprophylaxis for 6 months appears to be cost-effective in patients with cancer who are at intermediate-to-high risk for VTE. The implementation of this strategy in patients with Khorana scores ≥3 may lead to the highest cost-benefit ratio.

Four-year trends in oral anticoagulant use and declining rates of ischemic stroke among 194,030 atrial fibrillation patients drawn from a sample of 12 million people.

BACKGROUND: Administrative data were used to investigate changes in hospitalizations for atrial fibrillation (AF), AF-related stroke, and treatment patterns between 2012 and 2016. METHODS: From the 'Ricerca e Salute' database, a population- and patient-based repository involving >12 million inhabitants and linking demographics, prescriptions, and hospital discharge records, all patients discharged alive with a diagnosis of AF between 2012 and 2015 were followed for 1 year. RESULTS: A total of 194,030 AF patients were included. The number of AF cases increased ~10% over time, from 4.0 per 1,000 inhabitants in 2012 to 4.4 per 1,000 in 2015. At 1 year, hospitalizations for ischemic stroke decreased from 21.3 per 1,000 patients with AF in 2012-2013 to 14.7 per 1,000 in 2015-2016 (-31%, 95% CI -18 to -41). Over the same period, oral anticoagulant (OAC) use increased from 56.7% to 64.4% (+14%, 95% CI +8 to +26), vitamin K antagonist use decreased (from 55.9 to 36.7%; -34%, 95% CI -21 to -44), whereas direct OACs (DOACs) increased (from <1% in 2012 to 27.7% in 2015). Antiplatelet prescriptions fell from 42.6% in 2012 to 28.1% in 2015. Hospitalizations for major bleeds, mainly gastrointestinal, increased from 1.5‰ in 2012-2013 to 2.3‰ in 2015-2016, whereas hemorrhagic stroke admissions decreased from 6.5‰ to 4.1‰. CONCLUSIONS: There was a slight increase in the prevalence of AF between 2012 and 2015, whereas the overall use of antiplatelet agents decreased and that of OAC, particularly DOACs, increased. Over the same period, 1-year hospitalizations for ischemic stroke declined substantially, with a declining rate of hemorrhagic strokes.

Cost-Effectiveness of Multigene Pharmacogenetic Testing in Patients With Acute Coronary Syndrome After Percutaneous Coronary Intervention.

OBJECTIVE: To evaluate the cost-effectiveness of multigene testing (CYP2C19, SLCO1B1, CYP2C9, VKORC1) compared with single-gene testing (CYP2C19) and standard of care (no genotyping) in acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI) from Medicare's perspective. METHODS: A hybrid decision tree/Markov model was developed to simulate patients post-PCI for ACS requiring antiplatelet therapy (CYP2C19 to guide antiplatelet selection), statin therapy (SLCO1B1 to guide statin selection), and anticoagulant therapy in those that develop atrial fibrillation (CYP2C9/VKORC1 to guide warfarin dose) over 12 months, 24 months, and lifetime. The primary outcome was cost (2016 US dollar) per quality-adjusted life years (QALYs) gained. Costs and QALYs were discounted at 3% per year. Probabilistic sensitivity analysis (PSA) varied input parameters (event probabilities, prescription costs, event costs, health-state utilities) to estimate changes in the cost per QALY gained. RESULTS: Base-case-discounted results indicated that the cost per QALY gained was $59 876, $33 512, and $3780 at 12 months, 24 months, and lifetime, respectively, for multigene testing compared with standard of care. Single-gene testing was dominated by multigene testing at all time horizons. PSA-discounted results indicated that, at the $50 000/QALY gained willingness-to-pay threshold, multigene testing had the highest probability of cost-effectiveness in the majority of simulations at 24 months (61%) and over the lifetime (81%). CONCLUSIONS: On the basis of projected simulations, multigene testing for Medicare patients post-PCI for ACS has a higher probability of being cost-effective over 24 months and the lifetime compared with single-gene testing and standard of care and could help optimize medication prescribing to improve patient outcomes.

Current status and factors influencing oral anticoagulant therapy among patients with non-valvular atrial fibrillation in Jiangsu province, China: a multi-center, cross-sectional study.

BACKGROUND: It has been reported that oral anticoagulation (OAC) is underused among Chinese patients with non-valvular atrial fibrillation (NVAF). Non-vitamin K antagonist oral anticoagulants (NOAC) have been recommended by recent guidelines and have been covered since 2017 by the Chinese medical insurance; thus, the overall situation of anticoagulant therapy may change. The aim of this study was to explore the current status of anticoagulant therapy among Chinese patients with NVAF in Jiangsu province. METHODS: This was a multi-center, cross-sectional study that was conducted in seven hospitals from January to September in 2017. The demographic characteristics and medical history of the patients were collected by questionnaire and from the medical records. Multivariate logistic regression was used to identify factors associated with anticoagulant therapy. RESULTS: A total of 593 patients were included in the analysis. A total of 35.6% of the participants received OAC (11.1% NOAC and 24.5% warfarin). Of those patients with a high risk of stroke, 11.1% were on NOAC, 24.8% on warfarin, 30.6% on aspirin, and 33.6% were not on medication. Self-paying, duration of AF ≥5 years were negatively associated with anticoagulant therapy in all patients (OR 1.724, 95% CI 1.086~2.794; OR 1.471, 95% CI 1.006~2.149, respectively), whereas, permanent AF was positively associated with anticoagulant therapy (OR 0.424, 95% CI 0.215~0.839). Among patients with high risk of stroke, self-paying and increasing age were negatively associated with anticoagulant therapy (OR 2.305, 95% CI 1.186~4.478; OR 1.087, 95% CI 1.041~1.135, respectively). CONCLUSIONS: Anticoagulant therapy is positively associated with permanent AF and negatively associated with self-paying, duration of AF > 5 years. Furthermore, the current status of anticoagulant therapy among Chinese patients with NVAF in Jiangsu province does not appear optimistic. Therefore, further studies should focus on how to improve the rate of OAC use among NVAF patients. In addition, policy makers should pay attention to the economic situation of the patients with NVAF using NOAC. TRIAL REGISTRATION: 2,017,029. Registered 20 March 2017 (retrospectively registered).

Are direct oral anticoagulants an economically attractive alternative to low molecular weight heparins in lung cancer associated venous thromboembolism management?

Venous thromboembolism is highly prevalent in lung cancer patients. Low molecular weight heparins are recommended for long term treatment of cancer associated venous thromboembolism. Direct oral anticoagulants are however an interesting alternative as they are administered orally and don't require monitoring. There are currently studies comparing both their efficacy and tolerance for cancer patients and more and more guidelines suggest considering direct oral anticoagulants for cancer associated venous thromboembolism treatment. The objective of this study was to evaluate the budgetary impact that direct oral anticoagulants use would have for lung cancer associated venous thromboembolism treatment and prevention in France. An economic model was made to evaluate the cost of venous thromboembolism treatment and prevention among patients with primary lung cancer in France by two strategies: current guidelines versus direct oral anticoagulants use. The model was fed with clinical and economic data extracted from the French national health information system. The analysis was conducted from the national mandatory Health insurance point of view. The time horizon of the study was the evaluation of the annual management cost. Lung cancer associated venous thromboembolism management's mean cost was estimated of 836€ per patient, that is a total cost of about 40 million euros per year at a national level. A 76% decrease of this cost can be expected with direct oral anticoagulants use. However, despite their benefits, these treatments raise new issues (medication interactions, bleeding management), and would likely not be recommended for all patients.

Cost-effectiveness microsimulation of catheter-directed thrombolysis in submassive pulmonary embolism using a right ventricular function model.

Approximately 30-50% of hemodynamically stable patients presenting with acute pulmonary embolism (PE) have evidence of right ventricular (RV) dysfunction. These patients are classified as submassive PE and the role of reperfusion therapy remains unclear. We sought to identify the circumstances under which catheter-directed thrombolysis (CDT) would represent high-value care for submassive PE. We used a computer-based, individual-level, state-transition model with one million simulated patients to perform a cost-effectiveness analysis comparing the treatment of submassive PE with CDT followed by anticoagulation to treatment with anticoagulation alone. Because RV function impacts prognosis and is commonly used in PE outcomes research, our model used RV dysfunction to differentiate health states. One-way, two-way, and probabilistic sensitivity analyses were used to quantify model uncertainty. Our base case analysis generated an incremental cost-effectiveness ratio (ICER) of $119,326 per quality adjusted life year. Sensitivity analyses resulted in ICERs consistent with high-value care when CDT conferred a reduction in the absolute probability of RV dysfunction of 3.5% or more. CDT yielded low-value ICERs if the absolute reduction was less than 1.56%. Our model suggests that catheter-directed thrombolytics represents high-value care compared to anticoagulation alone when CDT offers an absolute improvement in RV dysfunction of 3.5% or more, but there is substantial uncertainly around these results. We estimated the monetary value of clarifying the costs and consequences surrounding RV dysfunction after submassive PE to be approximately $268 million annually, suggesting further research in this area could be highly valuable.

A simple, cost-effective, and rapid separation process for the isolation of anticoagulant active fraction from the fruit extract of Momordica charantia: Characterization of bioactive components and anticoagulant mechanism of active fraction in a mouse model.

A simple, rapid, and cost-effective process for the separation of an active anticoagulant fraction from the aqueous fruit extract of Momordica charantia by using rice husk as adsorbed is described. The in vitro anticoagulant activity of active anticoagulant fraction was comparable to commercial anticoagulants heparin and warfarin. Phytochemical analysis revealed the presence of alkaloids, flavonoids, and phytols in the active anticoagulant fraction, nevertheless; it was devoid of glycosides, triterpenoids, tannins, saponins, steroids, and carbohydrates. By gas chromatography with mass spectrometry analysis, decanoic acid, 1,2,3-propanetriyl ester (22.3%), dodecanoic acid, 1,2,3-propanetriyl ester-d5 (17.3%), dodecenoic acid, 1,2,3-propanetriyl ester (12.5%), and 4-B-methylandrostane 2,3-diol-1,17-dione (11.4%) were identified as the most abundant constituents of active anticoagulant fraction. Presence of αß-fibrinogenase enzyme was identified by biochemical assay but not by liquid chromatography with tandem mass spectrometry analysis suggesting presence of a novel protease enzyme in this fraction. The active anticoagulant fraction demonstrated biding to fibrinogen but not to thrombin or Factor Xa, inhibited the collagen/ADP-induced mammalian platelet aggregation, showed in vitro thrombolytic activity, noncytotoxic to mammalian cells, showed in vivo plasma defibrinogenation and anticoagulant activities, and inhibited k-carrageen-induced thrombus formation in the tails of mice. Therefore, active anticoagulant fraction (an herbal drug) may find therapeutic application for the prevention and/or treatment of hyperfibrinogenemia/thrombosis-associated cardiovascular disorders.

The speed of adoption of new drugs and prescription volume after the amendments in reimbursement coverage: the case of non-vitamin K antagonist oral anticoagulants in South Korea.

BACKGROUND: The speed of adoption of new drugs and frequencies of substitutions leads to changes in health care expenditures as well as patient outcomes. In this study, we aim to understand the speed of adoption of new drugs and their prescription volume in health care institutions and evaluate the impact of policy options to manage pharmaceutical expenditure. METHODS: We conducted a retrospective cohort study of health care institutions prescribing NOACs, including Apixaban, Dabigatran, and Rivaroxaban, to address the speed of adoption and their substitution from October 1, 2010, through December 31, 2015, using the National Health Insurance Service-National Sample Cohort. Two threshold time points, including the extension of reimbursement with the need for the letter of opinion and the withdrawal of the letter of opinion, were noted in this study. Then, we applied a survival analysis to elucidate factors that affected the speed of adoption of NOACs, and interrupted time series analysis to estimate the effect of amendments in reimbursement coverage in prescription volume. RESULTS: Among 934 health care institutions in a study population, 334 institutions (36%) had prescribed NOACs at least one time during the study period, indicating that health care institutions were conservative in adopting new drugs. However, the speed of adoption was related to the characteristics of health care institution. We also found that prescriptions of NOACs before the withdrawal of the need for the letter of opinion were marginal, and the prescription volume of NOACs was significantly increased after the withdrawal of a letter of opinion. CONCLUSIONS: Health care institutions were conservative in adopting new drugs, and the speed of adoption is not closely related to an increased prescription volume in the short run. Thus, policies that are centered on managing pharmaceutical expenditure should be devised with considering the impact of introducing new drugs in the long run. A letter of opinion, which was devised to manage prescriptions of NOACs, was effective in managing pharmaceutical expenditures in health care institutions, particularly for tertiary institutions. Conversely, the withdrawal of the need for the letter of opinion should be implemented with caution.

Warfarin control in Hong Kong clinical practice: a single-centre observational study.

INTRODUCTION: Time in therapeutic range (TTR) assesses the safety and effectiveness of warfarin therapy using the international normalised ratio. This study investigated the TTR in Hong Kong patients using both European and Japanese therapeutic ranges and patients' economic and clinical outcomes. Predictors of poor warfarin control and patient knowledge concerning warfarin therapy were assessed. METHODS: A 5-month observational study with retrospective and prospective components was conducted in the Prince of Wales Hospital. The study examined electronic patient records of patients who received warfarin for at least 1 year during the period from January 2010 to August 2015. Patient knowledge was assessed via phone interview using the Oral Anticoagulation Knowledge (OAK) test. RESULTS: In total, 259 patients were included; 174 completed the OAK test. The calculated mean TTR was 40.2±17.1% (European therapeutic range), compared with 49.1±16.1% (Japanese therapeutic range) [P<0.001]. Mean TTR was higher in patients with atrial fibrillation than in patients with prosthetic heart valve (P<0.001). The abilities of TTR to predict clinical and economic outcomes were comparable between European and Japanese therapeutic ranges. Patients with ideal TTR had fewer clinical complications and lower healthcare costs. Patients with younger age exhibited worse TTR, as did those with concurrent use of furosemide, famotidine, or simvastatin. Mean OAK test score was 54.1%. Only 24 (13.8%) patients achieved a satisfactory overall score of ≥75% in the test. CONCLUSION: Warfarin use in Hong Kong patients was poorly controlled, regardless of indication. Patient knowledge concerning warfarin use was suboptimal; thus, additional patient education is warranted regarding warfarin.

Cost-Effectiveness Analysis of Non-Vitamin K Antagonist Oral Anticoagulants Versus Warfarin in Thai Patients With Non-Valvular Atrial Fibrillation.

BACKGROUND: Non-vitamin K antagonist oral anticoagulants (NOACs) have been recommended as preferred options for stroke prevention in patients with atrial fibrillation (AF) versus warfarin by guidelines worldwide. AIM: This study aimed to evaluate the cost-effectiveness of each NOAC in a Thai health care environment, a country with upper middle-income economies based on the World Bank's classification. METHOD: A lifetime Markov model was created from a Thai societal perspective. The model consisted of 19 health states separated into two cycles: event cycle and consequence cycle. The consequences of AF included in the model were ischaemic stroke, intracranial haemorrhage, extracranial haemorrhage, and myocardial infarction. All NOACs available in Thailand (dabigatran 150 mg and 110 mg twice daily; rivaroxaban 20 mg once daily; apixaban 5 mg twice daily; edoxaban 60 mg and 30 mg once daily) were assessed using warfarin with an international normalised ratio of 2-3 as the reference. Inputs were a combination of published literature and local data when available. A willingness-to-pay of 160,000 Thai baht (THB)/quality-adjusted life year (QALY) was used as the threshold of being cost-effective. Incremental cost-effectiveness ratios and cost-effectiveness acceptability curves were estimated. RESULTS: All NOACs were not cost-effective strategies for the Thai AF population. The ranking of incremental cost-effectiveness ratios from lowest to highest were apixaban 5 mg twice daily (THB 692,136 or US$21,862) followed by edoxaban 60 mg once daily (THB 911,772 or US$28,799), edoxaban 30 mg once daily (THB 913,749 or US$28,861), dabigatran 150 mg twice daily (THB 1,102,106 or US$34,811), dabigatran 110 mg twice daily (THB 1,195,347 or US$37,756), and rivaroxaban 20 mg once daily (THB 1,347,650 or US$42,566). Cost-effectiveness acceptability curve indicated that apixaban had the highest potential to be a cost-effective strategy versus other NOACs. CONCLUSIONS: Our findings indicated that all NOACs were not cost-effective in the Thai AF population. Of the NOACs, apixaban may be the most likely to be cost-effective. These data may be useful for policymakers to perform a comprehensive evaluation of these agents for formulary decision and pricing negotiation.

Oral Anticoagulants - Utilisation and Expenditure under the Community Drugs Schemes.

Aims This study determined the impact of the direct oral anticoagulants (DOACs) on the utilisation and expenditure on oral anticoagulants (OACs) in the Irish Community healthcare setting. We also investigated aspects of DOAC prescribing. Methods Using anonymised prescription data from the HSE pharmacy claims database we investigated anticoagulant prescribing over the study period (1/1/2014 - 31/12/2018). Results Some 74,748 patients were being treated with OACs by the year end 2018 an increase of 30,319 over 5 years. Warfarin prescribing fell from 32,751 patients in 2014 to 16,166 by the year end 2018. Apixaban is the most frequently prescribed OAC and annual expenditure on DOACs now exceeds € 51 million. Patients treated with DOACs are older than participants in the pivotal clinical trials and are frequently co-administered interacting drugs. Conclusion The introduction of DOACs has resulted in an overall increase in anticoagulant prescribing, a significant reduction in warfarin usage and a large increase in expenditure.

[The cost of pulmonary thromboembolism treatment]. / Pulmoner tromboemboli tedavisinde maliyet.

INTRODUCTION: Primary aim of this study is to determine the financial burden of Vitamin K Antagonists (VKA), low molecular weight heparins (LMWH) and new oral anticoagulants (NOAC) which are used in the treatment of the pulmonary thromboembolism (PTE). Secondary aim is to show long term complications of the treatment options. MATERIALS AND METHODS: The patients who are diagnosed with PTE between May 2016 and March 2018 at Faculty of Medicine Karadeniz Technical University Hospital were observed prospectively. Hospitalization costs were calculated on patients who were treated only for PTE by hospitalized in the Chest Diseases Service in the acute period. Maintenance costs were calculated over all patients who regulary admitted to our outpatient clinic with the diagnosis of PTE. Data were presented as mean ± SD and median ± interquartilee range. A p-value of <0.05 was accepted to be significant. RESULT: Fifty five (37.2%) of the patients were male, 93 (62.8%) were female and the median age was 68 (range 18-95). The median hospitalization time and cost of patients who are discharged with VKA (n: 22) compared with patients discharged with LMWH (n: 22) was found to be increased (1316.82 TL 7,5 days / 803.36 TL, 5 days p<0.001). Statistical analysis could not be performed with NOAC (n: 2). In the analysis of sixth month costs, LMWH cost was found to be higher than VKA cost (6.927.15 ± 2.687.67 TL/698.29 ± 483.51 TL p<0.001). However VKA treatment tended to be less expensive than treatment with NOACs (698.29 ± 483.51 TL/1.050.81 ± 300.28 TL p= 0.140). CONCLUSIONS: In the acute period of PTE, VKA increases the length of hospitalization and hospital costs in patients treated at the hospital. In the maintenance period, VKA tends to have a lower cost compared to NOACs.