Coordination of oral anticoagulant care at hospital discharge (COACHeD): pilot randomised controlled trial.

OBJECTIVES: To evaluate whether a focused, expert medication management intervention is feasible and potentially effective in preventing anticoagulation-related adverse events for patients transitioning from hospital to home. DESIGN: Randomised, parallel design. SETTING: Medical wards at six hospital sites in southern Ontario, Canada. PARTICIPANTS: Adults 18 years of age or older being discharged to home on an oral anticoagulant (OAC) to be taken for at least 4 weeks. INTERVENTIONS: Clinical pharmacologist-led intervention, including a detailed discharge medication management plan, a circle of care handover and early postdischarge virtual check-up visits to 1 month with 3-month follow-up. The control group received the usual care. OUTCOMES MEASURES: Primary outcomes were study feasibility outcomes (recruitment, retention and cost per patient). Secondary outcomes included adverse anticoagulant safety events composite, quality of transitional care, quality of life, anticoagulant knowledge, satisfaction with care, problems with medications and health resource utilisation. RESULTS: Extensive periods of restriction of recruitment plus difficulties accessing patients at the time of discharge negatively impacted feasibility, especially cost per patient recruited. Of 845 patients screened, 167 were eligible and 56 were randomised. The mean age (±SD) was 71.2±12.5 years, 42.9% females, with two lost to follow-up. Intervention patients were more likely to rate their ability to manage their OAC as improved (17/27 (63.0%) vs 7/22 (31.8%), OR 3.6 (95% CI 1.1 to 12.0)) and their continuity of care as improved (21/27 (77.8%) vs 2/22 (9.1%), OR 35.0 (95% CI 6.3 to 194.2)). Fewer intervention patients were taking one or more inappropriate medications (7 (22.5%) vs 15 (60%), OR 0.19 (95% CI 0.06 to 0.62)). CONCLUSION: This pilot randomised controlled trial suggests that a transitional care intervention at hospital discharge for older adults taking OACs was well received and potentially effective for some surrogate outcomes, but overly costly to proceed to a definitive large trial. TRIAL REGISTRATION NUMBER: NCT02777047.

Effectiveness, utilisation and cost associated with implantable loop recorders versus external monitors after ischaemic or cryptogenic stroke.

OBJECTIVE: Implantable loop recorders (ILRs) are increasingly used for long-term rhythm monitoring after ischaemic and cryptogenic stroke, with the goal of detecting atrial fibrillation (AF) and subsequent initiation of oral anticoagulation to reduce risk of adverse clinical outcomes. There is a need to determine the effectiveness of different rhythm monitoring strategies in this context. METHODS: We conducted a retrospective cohort analysis of individuals with commercial and Medicare Advantage insurance in Optum Labs Data Warehouse who had incident ischaemic or cryptogenic stroke and no prior cardiovascular implantable electronic device from 1 January 2016 to 30 June 2021. Patients were stratified by rhythm monitoring strategy: ILR, long-term continuous external cardiac monitor (>48 hours to 30 days) or Holter monitor (≤48 hours). The primary outcome was risk-adjusted all-cause mortality at 12 months. Secondary outcomes included new diagnosis of AF and oral anticoagulation, bleeding, and costs. RESULTS: Among 48 901 patients with ischaemic or cryptogenic stroke, 9235 received an ILR, 29 103 long-term continuous external monitor and 10 563 Holter monitor only. Mean age was 69.9 (SD 11.9) years and 53.5% were female. During the 12-month follow-up period, patients who received ILRs compared with those who received long-term continuous external monitors had a higher odds of new diagnosis of AF and oral anticoagulant initiation (adjusted OR 2.27, 95% CI 2.09 to 2.48). Compared with patients who received long-term continuous external monitors, those who received ILRs had similar 12-month mortality (HR 1.00; 95% CI 0.89 to 1.12), with approximately $13 000 higher costs at baseline (including monitor cost) and $2500 higher costs during 12-month follow-up. CONCLUSIONS: In this large real-world study of patients with ischaemic or cryptogenic stroke, ILR placement resulted in more diagnosis of AF and initiation of oral anticoagulation, but no difference in mortality compared with long-term continuous external monitors.

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.

Trends in Oral Anticoagulant Use and Individual Expenditures Across the United States from 2014 to 2020.

BACKGROUND: Landmark clinical trials have expended the indications for the direct oral anticoagulants (DOACs), but contemporary data on usage and expenditure patterns are lacking. OBJECTIVE: This study aimed to assess annual trends in oral anticoagulant (OAC) utilization and expenditure across the United States (US) from 2014 to 2020. METHODS: We utilized the Medical Expenditure Panel Survey (MEPS) to study the trends of use and expenditures of warfarin, dabigatran, rivaroxaban, apixaban, and edoxaban between 2014 and 2020 in the US. Survey respondents reported OAC use within the past year, which was verified against pharmacy records. Payment information was obtained from the respondent's pharmacy and was categorized as third-party or self/out-of-pocket. Potential indications and medical conditions of interest for OAC therapy were identified from respondent-reported medical conditions. We estimated the national number of OAC users and total expenditures across age, sex, race, ethnicity, insurance, and medical condition subgroups. Trends of OAC users' characteristics, expenditure, and number of prescriptions were evaluated using the Mann-Kendall test for trends. RESULTS: Between 2014 and 2020, the number of warfarin users decreased from 3.8 million (70% of all OAC users) to 2.2 million (p = 0.007) [29% of all OAC users], while the number of DOAC users increased from 1.6 million (30% of all OAC users) to 5.4 million (p = 0.003) [70% of all OAC users]. The total expenditure of OACs in the US increased from $3.4 billion in 2014 to $17.8 billion in 2020 (p = 0.003), which was driven by the increase in DOAC expenditures (p = 0.003). CONCLUSIONS: DOACs have replaced warfarin as the preferred OAC in the US. The increased costs associated with DOAC use may decline when generic formulations are approved.

Payer approval and rejection of oral anticoagulant prescriptions and prescription abandonment patterns among patients with venous thromboembolism.

BACKGROUND: Venous thromboembolism (VTE) is a major public health condition that renders patients at risk of recurrent events, which significantly increases their morbidity, mortality, and health care costs. Apart from warfarin, direct oral anticoagulants, such as apixaban, dabigatran, or rivaroxaban, are approved for VTE treatment. Cardiovascular drugs are largely impacted by formulary restrictions; however, the impact on oral anticoagulants (including warfarin and direct oral anticoagulants) in VTE has not been well studied. OBJECTIVE: To describe the extent of payer-rejected claims for oral anticoagulants for VTE and the factors associated with rejected claims. Prescription abandonment of oral anticoagulants and the time to an eventual fill for oral anticoagulant after rejection or abandonment were also evaluated. METHODS: A retrospective cohort study was conducted among patients with VTE newly prescribed an oral anticoagulant (first claim was the index) between October 2016 and October 2021. Descriptive statistics were used to describe the proportion of patients with paid (ie, filled), rejected, or abandoned index oral anticoagulant prescription and journey to paid prescription among those with initial rejection. Multivariable logistic regression was used to identify factors associated with initial rejection. RESULTS: Among the overall sample (N = 297,312), 74.3% had initial oral anticoagulant prescriptions approved, 9.1% had them rejected, and 16.7% abandoned them. Of the patients with initial rejection, 82.1% eventually filled their oral anticoagulant prescriptions; however, for 14.2% of these patients, the first fill was for an oral anticoagulant other than that initially prescribed. The mean time to a first fill for an oral anticoagulant after an initial rejection was 18.3 days. More than half of the patients with an initial rejected oral anticoagulant claim had at least 1 additional rejection during the follow-up period. Of the patients who abandoned their initial oral anticoagulant prescription, 83.9% filled an oral anticoagulant prescription during follow-up; the mean time to fill for the index oral anticoagulant was 15.6 days. Oral anticoagulant type, Medicare payer coverage, prescribing physician specialty, and VTE diagnosis setting of care were significantly associated with index oral anticoagulant claim rejection (P < 0.05). CONCLUSIONS: Rejection and abandonment may delay access to oral anticoagulant treatment. Factors contributing to these scenarios should be understood and addressed for proper VTE management.

Methods for Economic Evaluations of Novel Oral Anticoagulants in Patients with Atrial Fibrillation: A Systematic Review.

BACKGROUND: Atrial fibrillation (AF) is a severe epidemiological and public health concern among the elderly population worldwide, with substantial economic and social burdens. Economic evaluations can play an essential role in optimizing the utilization of scarce resources. In recent years, the number of economic evaluation studies related to AF has increased due to the rising number of AF patients, the continuous updating of clinical data, and the emergence of real-world evidence. However, there are still deficiencies in model settings and parameter sources in relevant studies. OBJECTIVE: This study aims to review the existing economic evaluations of novel oral anticoagulants (NOACs) in patients with AF and summarize the evidence and methods applied. METHODS: A comprehensive and systematic search was conducted on electronic databases, including PubMed, Embase, Web of Science (WOS), and The Cochrane Library, from the date of database creation to November 2022. The reporting quality of included literature was assessed using the Consolidated Health Economic Evaluation Reporting Standards 2022 (CHEERS 2022) statement. RESULTS: A total of 102 studies were included in the review, with 200 comparisons between NOACs and vitamin K antagonists (VKAs), as well as 58 comparisons between different NOACs. The healthcare sector and payer perspectives were the most common, and accordingly, the majority of the evaluations considered only direct medical costs. Most studies used Markov cohort models with the number of health states ranging from 4 to 29. Of included studies, 80 (78%) considered event recurrence and complications, and 78 (76%) considered discontinuation and second-line therapy. All of the studies applied uncertainty analysis to explore the robustness of the results. Of all 200 NOACs-VKAs comparisons, 149 (75%) showed that NOACs were more cost-effective; this proportion was 84% (139 out of 165) in high-income countries but decreased to 29% (10 out of 35) in middle- and low-income countries. Most (82%) of the 28 items in the CHEERS 2022 checklist were elucidated in the majority of included studies. A minority (only 39%) of included studies demonstrated high reporting quality. CONCLUSION: NOACs may be more cost-effective than VKAs in patients with AF, but this conclusion applies to high-income countries, whereas VKAs may be more cost-effective in middle- and low-income countries. The reporting quality of included studies was variable, and certain methodological issues were presented. This study highlights the economic evaluation methodology of NOACs in patients with AF and provides recommendations for modeling methods and future studies.

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.

Contemporary clinical and economic outcomes among oral anticoagulant treated and untreated elderly patients with atrial fibrillation: Insights from the United States Medicare database.

BACKGROUND: Oral anticoagulants (OACs) mitigate the risk of stroke in atrial fibrillation (AF) patients. OBJECTIVE: Elderly AF patients who were treated with OACs (apixaban, dabigatran, edoxaban, rivaroxaban, or warfarin) were compared against AF patients who were not treated with OACs with respect to their clinical and economic outcomes. METHODS: Newly diagnosed AF patients were identified between January 2013 and December 2017 in the Medicare database. Evidence of an OAC treatment claim on or after the first AF diagnosis was used to classify patients into treatment-defined cohorts, and these cohorts were further stratified based on the initial OAC prescribed. The risks of stroke/systemic embolism (SE), major bleeding (MB), and death were analyzed using inverse probability treatment weighted time-dependent Cox regression models, and costs were compared with marginal structural models. RESULTS: The two treatment groups were composed of 1,421,187 AF patients: OAC treated (N = 583,350, 41.0% [36.4% apixaban, 4.9% dabigatran, 0.1% edoxaban, 26.7% rivaroxaban, and 31.9% warfarin patients]) and untreated (N = 837,837, 59.0%). OAC-treated patients had a lower adjusted risk of stroke/SE compared to untreated patients (hazard ratio [HR]: 0.70; 95% confidence interval [CI]: 0.68-0.72). Additionally patients receiving OACs had a lower adjusted risk of death (HR: 0.56; 95% CI: 0.55-0.56) and a higher risk of MB (HR: 1.57; 95% CI: 1.54-1.59) and this trend was consistent across each OAC sub-group. The OAC-treated cohort had lower adjusted total healthcare costs per patient per month ($4,381 vs $7,172; p < .0001). CONCLUSION: For the OAC-treated cohort in this elderly US population, stroke/SE and all-cause death were lower, while risk of MB was higher. Among OAC treated patients, total healthcare costs were lower than those of the untreated cohort.

A Systematic Review of Economic Aspects of Service Interventions to Increase Anticoagulation Use in Atrial Fibrillation.

OBJECTIVE: To systematically identify and appraise existing evidence surrounding economic aspects of anticoagulation service interventions for patients with atrial fibrillation. METHODS: We searched the published and grey literature up to October 2019 to identify relevant economic evidence in any health care setting. A narrative-synthesis approach was taken to summarise evidence by economic design and type of service intervention, with costs expressed in pound sterling and valued at 2017 to 2018 prices. RESULTS: A total of 13 studies met our inclusion criteria from 1,168 papers originally identified. Categories of interventions included anticoagulation clinics (n = 4), complex interventions (n = 4), decision support tools (n = 3) and patient-centred approaches (n = 2). Anticoagulation clinics were cost-saving compared with usual care (range for mean cost difference: £188-£691 per-patient per-year) with equivalent health outcomes. Only one economic evaluation of a complex intervention was conducted; case management was more expensive than usual care (mean cost difference: £255 per-patient per-year) and the probability of its cost-effectiveness did not exceed 70%. There was limited economic evidence surrounding decision support tools or patient-centred approaches. Targeting service interventions at high-risk groups and those with suboptimal treatment was most likely to result in cost savings. CONCLUSION: This review revealed some evidence to support the cost-effectiveness of anticoagulation clinics. However, summative conclusions are constrained by a paucity of economic evidence, a lack of direct comparisons between interventions, and study heterogeneity in terms of intervention, comparator and study year. Further research is urgently needed to inform commissioning and service development. Data from this review can inform future economic evaluations of anticoagulation service interventions.

Primary care provider payment models and adherence to anticoagulation in patients with atrial fibrillation.

BACKGROUND: Oral anticoagulation (OAC) is recommended for the prevention of stroke in atrial fibrillation (AF). However, only 50%-60% of AF patients in the United States are treated with OAC, and 60% of them adhere to OAC therapy over time. OBJECTIVES: To (1) compare adherent use of OAC between AF patients who received primary care from practices involved in shared-savings models and patients who received care from practices not involved in shared savings and (2) examine the trend of adherence to OAC over time. Because OAC can save downstream medical costs associated with averted stroke events, we hypothesized that OAC adherence would be higher among patients receiving care from practices involved in shared savings. METHODS: Using 2014-2019 claims data from a health insurer in western Pennsylvania, we identified 20,637 AF patients from 2015-2018. Patients were followed from the first AF diagnosis (index date) for 12 months or until disenrollment. We categorized patients according to the payment model of the practice from which they received primary care: shared savings (n = 8,844) and no shared savings (n = 11,793). The primary outcome was adherent use of OAC therapy, which was defined as having at least 80% of the followup period covered with OAC. Secondary outcomes included adherent use of direct oral anticoagulants (DOACs) and adherent use of warfarin. We constructed logistic regression models to assess the association between involvement in shared savings and adherent use of OAC, while controlling for demographics, clinical characteristics, and index year. RESULTS: 34% of patients in the shared-savings group adhered to OAC, compared with 32.7% in the no shared-savings group (P = 0.04). After adjustment, adherence was higher for the shared-savings group for OAC (adjusted odds ratio [aOR] = 1.07, 95% CI = 1.01-1.14) and warfarin (aOR = 1.11, 95% CI = 1.02-1.20) compared with the no shared-savings group. However, the odds of adherent use of DOACs did not statistically differ between shared savings and no shared savings (aOR = 0.99, 95% CI = 0.91-1.08). The odds of adherent OAC use increased over time: the aOR of adherent use of OAC was 1.21 (95% CI = 1.09-1.34) for index year 2016; 1.50 (95% CI = 1.36-1.67) for 2017; and 1.78 (95% CI 1.60-1.98) for 2018, all compared with 2015. CONCLUSIONS: Receipt of primary care from a practice involved in shared savings was associated with a higher adherent use of OAC and warfarin for patients with atrial fibrillation. Furthermore, adherent use of OAC improved over time for both treatment groups. Our research demonstrates that the alignment of financial incentives between providers and insurers may improve the use of therapies with downstream cost-saving potential. DISCLOSURES: This project was funded by the National Heart, Lung and Blood Institute (grant number K01HL142847). Hernandez has received consulting fees from Pfizer and BMS, outside of the submitted work. The other authors have nothing to disclose.

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.

Comparing total medical expenditure between patients receiving direct oral anticoagulants vs warfarin for the treatment of atrial fibrillation: evidence from VA-Medicare dual enrollees.

BACKGROUND: Direct oral anticoagulants (DOACs) are an alternative to warfarin for treatment of atrial fibrillation (AF). Evidence demonstrating the efficacy and safety of DOACs has primarily been from clinical trial settings. The real-world effectiveness of DOACs in specific nontrial populations that differ in age, comorbidity burden, and socioeconomic status is unclear. OBJECTIVE: To compare total downstream medical expenditure between AF patients treated with warfarin and DOACs dually enrolled in the Veterans Affairs (VA) Healthcare System and fee-for-service Medicare. METHODS: This was an exploratory treatment effectiveness study that analyzed VA administrative data and Medicare claims. We examined patients with an incident diagnosis for AF and initiated warfarin or DOAC treatment between 2012 and 2015. The primary outcome was total medical expenditure over 3 years following treatment initiation. To address potential informative censoring, we applied a multipart estimator that extends traditional 2-part models to separate differences between groups due to survival and cost accumulation effects. Inverse probability weighting was applied to address potential treatment selection bias. RESULTS: We identified 31,276 and 17,021 patients receiving warfarin and DOACs, respectively. Mean unadjusted (SD) expenditure was higher for warfarin ($56,265 [$96,666]) compared with DOAC patients ($32,736 [$52,470]). Compared with patients receiving DOACs, adjusted 3-year expenditure was $25,688 (P < 0.001) higher for patients receiving warfarin. CONCLUSIONS: VA patients with AF initiating warfarin incurred markedly higher downstream expenditure compared with similar patients receiving DOACs. The benefits of DOACs found in previous clinical trials were present in this population, suggesting that these DOACs may be the preferred option for treatment of AF in older VA patients. DISCLOSURES: This study was funded by a VA Health Services Research and Development Investigator Initiated Research Award (IIR 15-139). Support for VA/CMS data was provided by the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Health Services Research and Development, VA Information Resource Center (Project Numbers SDR 02-237 and 98-004). The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs, the University of Washington, Northeastern University, and Boston University. The authors declare no conflicts of interest. This research includes data obtained from the VHA Office of Performance Measurement (17API2), which resides within the Office of Analytics and Performance Integration (API), under the Office of Quality and Patient Safety (QPS; formerly known as RAPID). An oral presentation documenting a subset of the findings from this study was presented at the 2020 AcademyHealth Annual Research Meeting, delivered virtually on July 29, 2020.

Cost Conversations About Anticoagulation Between Patients With Atrial Fibrillation and Their Clinicians: A Secondary Analysis of a Randomized Clinical Trial.

Importance: How patients with atrial fibrillation (AF) and their clinicians consider cost in forming care plans remains unknown. Objective: To identify factors that inform conversations regarding costs of anticoagulants for treatment of AF between patients and clinicians and outcomes associated with these conversations. Design, Setting, and Participants: This cohort study of recorded encounters and participant surveys at 5 US medical centers (including academic, community, and safety-net centers) from the SDM4AFib randomized trial compared standard AF care with and without use of a shared decision-making (SDM) tool. Included patients were considering anticoagulation treatment and were recruited by their clinicians between January 30, 2017, and June 27, 2019. Data were analyzed between August and November 2019. Main Outcomes and Measures: The incidence of and factors associated with cost conversations, and the association of cost conversations with patients' consideration of treatment cost burden and their choice of anticoagulation. Results: A total of 830 encounters (out of 922 enrolled participants) were recorded. Patients' mean (SD) age was 71.0 (10.4) years; 511 patients (61.6%) were men, 704 (86.0%) were White, 303 (40.9%) earned between $40 000 and $99 999 in annual income, and 657 (79.2%) were receiving anticoagulants. Clinicians' mean (SD) age was 44.8 (13.2) years; 75 clinicians (53.2%) were men, and 111 (76%) practiced as physicians, with approximately half (69 [48.9%]) specializing in either internal medicine or cardiology. Cost conversations occurred in 639 encounters (77.0%) and were more likely in the SDM arm (378 [90%] vs 261 [64%]; OR, 9.69; 95% CI, 5.77-16.29). In multivariable analysis, cost conversations were more likely to occur with female clinicians (66 [47%]; OR, 2.85; 95% CI, 1.21-6.71); consultants vs in-training clinicians (113 [75%]; OR, 4.0; 95% CI, 1.4-11.1); clinicians practicing family medicine (24 [16%]; OR, 12.12; 95% CI, 2.75-53.38]), internal medicine (35 [23%]; OR, 3.82; 95% CI, 1.25-11.70), or other clinicians (21 [14%]; OR, 4.90; 95% CI, 1.32-18.16) when compared with cardiologists; and for patients with an annual household income between $40 000 and $99 999 (249 [82.2%]; OR, 1.86; 95% CI, 1.05-3.29) compared with income below $40 000 or above $99 999. More patients who had cost conversations reported cost as a factor in their decision (244 [89.1%] vs 327 [69.0%]; OR 3.66; 95% CI, 2.43-5.50), but cost conversations were not associated with the choice of anticoagulation agent. Conclusions and Relevance: Cost conversations were common, particularly for middle-income patients and with female and consultant-level primary care clinicians, as well as in encounters using an SDM tool; they were associated with patients' consideration of treatment cost burden but not final treatment choice. With increasing costs of care passed on to patients, these findings can inform efforts to promote cost conversations in practice. Trial Registration: ClinicalTrials.gov Identifier: NCT02905032.

Short- and Long-term Health Care Resource Utilization and Costs Following Intracerebral Hemorrhage.

OBJECTIVE: We sought to evaluate the short- and long-term resource use and costs associated with intracerebral hemorrhage (ICH) taken from an entire population. We in addition sought to evaluate the association of oral anticoagulation (OAC) and health care costs. METHODS: This was a retrospective cohort study of adult patients (≥18 years) with ICH in the entire population of Ontario, Canada (2009-2017). We captured outcomes through linkage to health administrative databases. We used generalized linear models to identify factors associated with total cost. Analysis of OAC use was limited to patients ≥66 years of age. The primary outcome was total 1-year direct health care costs in 2020 US dollars. RESULTS: Among 16,248 individuals with ICH (mean age 71.2 years, male 52.3%), 1-year mortality was 46.0%, and 24.2% required mechanical ventilation. The median total 1-year cost was $26,886 (interquartile range [IQR] $9,641-$62,907) with costs for those who died in hospital of $7,268 (IQR $4,031-$14,966) vs $44,969 (IQR $20,264-$82,414, p < 0.001) for survivors to discharge. OAC use (analysis limited to individuals ≥66 years old) was associated with higher total 1-year costs (cost ratio 1.06 [95% confidence interval 1.01-1.11]). Total 1-year costs for the entire cohort exceeded $120 million per year over the study period. CONCLUSIONS: ICH is associated with significant health care costs, and the median cost of a patient with ICH is roughly 10 times the median inpatient cost in Ontario. Costs were higher among survivors than deceased patients. OAC use is independently associated with increased costs. To maximize cost-effectiveness, future therapies for ICH must aim to reduce disability, not only improve mortality.

A meta-analysis and cost-minimization analysis of bivalirudin versus heparin in high-risk patients for percutaneous coronary intervention.

This meta-analysis was performed to compare the safety, efficacy, and pharmacoeconomic of bivalirudin versus heparin in high-risk patients for percutaneous coronary interventions (PCI). Earlier meta-analysis comparing bivalirudin and heparin during PCI demonstrated that bivalirudin caused less bleeding with more stent thrombosis. However, little data were available on the safety of bivalirudin versus heparin in high-risk patients for PCI. Thus, we performed a meta-analysis to evaluate the efficacy and safety in the "high-risk" patients. A systematic search of electronic databases was conducted up to July 30, 2020. The Cochrane Risk of Bias assessment tool was used to assess the quality of included studies. The primary outcomes were all-cause death and major adverse cardiac events (MACE); secondary outcomes were major and minor bleeding, followed by a cost-minimization analysis comparing bivalirudin and heparin using a local drug and medical costs reported in China. Subgroup analysis was based on the type of disease of the high-risk population. Finally, a total of 10 randomized controlled trials involved 42,699 patients were collected. The Cochrane Risk of Bias Tool was employed to appraise the research quality. No significant difference was noted between bivalirudin and heparin regarding all-cause death and MACE. However, subgroup analysis showed that bivalirudin caused less major bleeding in female (OR:0.65, 95% CI:0.53-0.79), diabetes (OR:0.55, 95%CI:0.42-0.73), and CKD (OR:0.59, 95%CI:0.63-1.65). The scatterers of the included literature were approximately symmetrical, and no research was outside the funnel plot. Additionally, cost-minimization analysis showed that heparin was likely to represent a cost-effective option compared with bivalirudin in China, with potential savings of 2129.53 Chinese Yuan (CNY) per patient for one PCI. Overall, the meta-analysis showed that although bivalirudin appeared to have a lower risk of major bleeding rate, the overall effectiveness and safety between the two groups showed no significant difference in high-risk patients for PCI. But the results of the cost-minimization analysis showed that heparin could be a potential cost-saving drug than bivalirudin in patients for PCI in China.

A tale of two centers: Is low-molecular-weight heparin really superior for prevention of posttraumatic venous thromboembolism?

BACKGROUND: Low-molecular-weight heparin (LMWH) is widely used for venous thromboembolism chemoprophylaxis following injury. However, unfractionated heparin (UFH) is a less expensive option. We compared LMWH and UFH for prevention of posttraumatic deep venous thrombosis (DVT) and pulmonary embolism (PE). METHODS: Trauma patients 15 years or older with at least one administration of venous thromboembolism chemoprophylaxis at two level I trauma centers with similar DVT-screening protocols were identified. Center 1 administered UFH every 8 hours for chemoprophylaxis, and center 2 used twice-daily antifactor Xa-adjusted LMWH. Clinical characteristics and primary chemoprophylaxis agent were evaluated in a two-level logistic regression model. Primary outcome was incidence of DVT and PE. RESULTS: There were 3,654 patients: 1,155 at center 1 and 2,499 at center 2. The unadjusted DVT rate at center 1 was lower than at center 2 (3.5% vs. 5.0%; p = 0.04); PE rates did not significantly differ (0.4% vs. 0.6%; p = 0.64). Patients at center 2 were older (mean, 50.3 vs. 47.3 years; p < 0.001) and had higher Injury Severity Scores (median, 10 vs. 9; p < 0.001), longer stays in the hospital (mean, 9.4 vs. 7.0 days; p < 0.001) and intensive care unit (mean, 3.0 vs. 1.3 days; p < 0.001), and a higher mortality rate (1.6% vs. 0.6%, p = 0.02) than patients at center 1. Center 1's patients received their first dose of chemoprophylaxis earlier than patients at center 2 (median, 1.0 vs. 1.7 days; p < 0.001). After risk adjustment and accounting for center effects, primary chemoprophylaxis agent was not associated with risk of DVT (odds ratio, 1.01; 95% confidence interval, 0.69-1.48; p = 0.949). Cost calculations showed that UFH was less expensive than LMWH. CONCLUSION: Primary utilization of UFH is not inferior to LMWH for posttraumatic DVT chemoprophylaxis and rates of PE are similar. Given that UFH is lower in cost, the choice of this chemoprophylaxis agent may have major economic implications. LEVEL OF EVIDENCE: Prognostic and epidemiological, level II; Therapeutic, level III.

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.

Posthospital discharge venous thromboembolism prophylaxis among colorectal and hepatobiliary surgeons: A practice survey.

BACKGROUND: Recent practice guidelines recommend venous thromboembolism prophylaxis for 28 days after cancer surgery. We sought to characterize and compare awareness, agreement, adoption, and adherence to these guidelines among surgeons. METHODS: We electronically surveyed Canadian hepatobiliary surgeons registered with the Canadian Hepatopancreatobiliary Association, general and colorectal surgeons registered with the College of Physicians and Surgeons of Ontario and the Canadian Society of Colorectal Surgeons who provide colorectal cancer care with a pilot-tested questionnaire. Attitudes to relevant guideline recommendations and perceived barriers to postdischarge venous thromboembolism prophylaxis were assessed on a 5-point Likert scale. RESULTS: There were 128 responses (response rate 60%, 128 of 213), including 60 general/colorectal and 68 hepatobiliary surgeons. Most surgeons were aware (122 of 128, 95%), agreed (101 of 122, 83%), adopted (78 of 101, 77%), and adhered (74 of 78, 95%) with guidelines. Preexisting venous thromboembolism-prophylaxis hospital programs, hepatobiliary surgeons, and geographical region were associated with increased likelihood of adherence. Among respondents that did not agree, insufficient evidence (median Likert: 4, interquartile range 3-5) and low incidence of venous thromboembolism (median Likert: 4, interquartile range 3-4) were cited as the strongest barriers. Surgeons who agreed but did not adopt these programs reported that the most significant barriers were "drug cost" (median Likert: 4, interquartile range 3-4) and "subcutaneous injections" (median Likert: 4, interquartile range 3-4). Surgeons that adhered additionally reported "logistical challenges of prescribing" as the greatest implementation barrier. CONCLUSION: Surgeons who remain apprehensive about postdischarge venous thromboembolism prophylaxis cite poor evidence and cost of the medication as the major barriers. Adherence was higher among hepatobiliary surgeons and at hospitals with existing venous thromboembolism-prophylaxis programs.