Background Heart failure presents a growing clinical and economic burden in the USA. Robust cost data on the burden of illness are critical to inform economic evaluations of new therapeutic interventions. Objectives This systematic literature review of heart failure-related costs in the USA aimed to assess the quality of the published evidence and provide a narrative synthesis of current data. Methods Four electronic databases (MEDLINE, EMBASE, EconLit, and the Centre for Reviews and Dissemination York Database, including the NHS Economic Evaluation Database and Health Technology Assessment Database) were searched for journal articles published between January 2014 and March 2020. The review, registered with PROSPERO (CRD42019134201), was restricted to cost-of-illness studies in adults with heart failure events in the USA. Results Eighty-seven studies were included, 41 of which allowed a comparison of cost estimates across studies. The annual median total medical costs for heart failure care were estimated at $24,383 per patient, with heart failure-specific hospitalizations driving costs (median $15,879 per patient). Analyses of subgroups revealed that heart failure-related costs are highly sensitive to individual patient characteristics (such as the presence of comorbidities and age) with large variations even within a subgroup. Additionally, differences in study design and a lack of standardized reporting limited the ability to compare cost estimates. The finding that costs are higher for patients with heart failure with reduced ejection fraction compared with patients with preserved ejection fraction highlights the need for differentiating among different heart failure types. Conclusions The review underpins the conclusion drawn in earlier reviews, namely that hospitalization costs are the key driver of heart failure-related costs. Analyses of subgroups provide a clearer understanding of sources of heterogeneity in cost data. While current cost estimates provide useful indications of economic burden, understanding the nuances of the data is critical to support its application. Electronic supplementary material The online version of this article (10.1007/s40273-020-00952-0) contains supplementary material, which is available to authorized users.

Objective To improve the efficiency and appropriateness of CT use in children with minor head trauma, clinical prediction rules were derived and validated by the Pediatric Emergency Care Applied Research Network (PECARN). The objective of this study was to conduct a cost-effectiveness analysis comparing the PECARN traumatic brain injury (TBI) prediction rules to usual care for selective CT use. Methods We used decision analytic modelling to project the outcomes, costs, and the cost-effectiveness of applying the PECARN rules compared with usual care in a hypothetical cohort of 1,000 children with minor blunt head trauma. Clinical management was directed by level of risk as specified by the presence or absence of variables in the PECARN TBI prediction rules. Immediate costs of care (diagnostic testing, treatment [not including clinician time], and hospital stay) were derived on single center data. Quality-adjusted life year (QALY) losses related to the sequelae of clinically important TBI (ciTBI) and to radiation-induced cancers, number of CT scans, radiation-induced cancers, missed ciTBI, and total costs were evaluated. Results Compared to the usual care strategy, the PECARN strategy was projected to miss slightly more children with ciTBIs (0.26 vs. 0.02 per 1000 children), but used fewer cranial CT scans (274 vs. 353), resulted in fewer radiation-induced cancers (0.34 vs. 0.45), cost less ($904,940 vs. $954,420), and had lower net QALY loss (−4.64 vs. −5.79). Because the PECARN strategy was more effective (less QALY loss) and less costly, it dominated the usual care strategy. Results were robust under sensitivity analyses. Conclusion Application of the PECARN TBI prediction rules for children with minor head trauma would lead to beneficial outcomes and more cost-effective care.

Background: An elevated level of low-density lipoprotein cholesterol (LDL-C) constitutes one of the most important modifiable risk factors for cardiovascular disease (CVD). Individuals with heterozygous familial hypercholesterolaemia (HeFH) are particularly vulnerable to CVD events. The addition of evolocumab to statins has shown marked reductions in LDL-C levels. The objective of this analysis is to demonstrate the clinical and economic value of LDL-C lowering with evolocumab from the Bulgarian public health care perspective. Methods: A disease-specific measure of health benefit was devised: Effectively treated patient-years (ETPYs) combine length of life with the likelihood of attaining best-practice recommendations on LDL-C lowering. “Effective treatment” was defined as a reduction in LDL-C levels of ≥50%. A Markov cohort state-transition model was adapted, considering a life-long treatment duration. Demographics, baseline characteristics and efficacy data were taken from the RUTHERFORD-2 trial. The model uses the relationship between LDL-C lowering and reduced CVD event rates observed in the meta-analyses conducted by the Cholesterol Treatment Trialists’ Collaboration. Outcomes and costs (from year 2015) were discounted at an annual rate of 5%. Sensitivity analyses were conducted to assess uncertainty surrounding the results. Results: The total incremental costs of evolocumab added to statins versus statins alone are BGN 120,329 while adding 9.30 ETPYs over lifetime. These results imply an incremental cost per ETPY of BGN 12,937 (US$ 7,215; € 6,604). The use of evolocumab is associated with a relative reduction in the CVD event rate by 38% (18% per 1 mmol/L). Conclusions: Adding evolocumab to statins may be considered cost-effective in light of an additional expense per patient-year gained in which individuals with HeFH receive effective treatment under the terms of international prevention guidelines. ETPYs are an intuitive and clinically meaningful measure of patient benefit that, in relation to costs, can support health care decision-making that considers quality of care.

Background and Objectives New treatments and interventions are in development to address clinical needs in heart failure. To support decision making on reimbursement, cost-effectiveness analyses are frequently required. A systematic literature review was conducted to identify and summarize heart failure utility values for use in economic evaluations. Methods Databases were searched for articles published until June 2019 that reported health utility values for patients with heart failure. Publications were reviewed with specific attention to study design; reported values were categorized according to the health states, 'chronic heart failure', 'hospitalized', and 'other acute heart failure'. Interquartile limits (25th percentile 'Q1', 75th percentile 'Q3') were calculated for health states and heart failure subgroups where there were sufficient data. Results The systematic literature review identified 161 publications based on data from 142 studies. Utility values for chronic heart failure were reported by 128 publications; 39 publications published values for hospitalized and three for other acute heart failure. There was substantial heterogeneity in the specifics of the study populations, methods of elicitation, and summary statistics, which is reflected in the wide range of utility values reported. EQ-5D was the most used instrument; the interquartile limit for mean EQ-5D values for chronic heart failure was 0.64-0.72. Conclusions There is a wealth of published utility values for heart failure to support economic evaluations. Data are heterogenous owing to specificities of the study population and methodology of utility value elicitation and analysis. Choice of value(s) to support economic models must be carefully justified to ensure a robust economic analysis.

Introduction To evaluate the cost-effectiveness of evolocumab when added to standard of care lipid-lowering treatment (LLT) for patients with atherosclerotic cardiovascular disease (ASCVD) who cannot adequately control their low-density lipoprotein cholesterol (LDL-C) despite optimized LLT in Canada. Methods An incremental cost-utility analysis was conducted using a Markov cohort state transition model adapted to the Canadian setting. Analyses were conducted from a public health and societal perspective using a lifetime time horizon for Canada. Scenario analyses were conducted on the basis of recommendations from the 2021 Canadian Cardiovascular Society (CCS) dyslipidemia guidelines. Results In ASCVD patients with prior myocardial infarction (MI) and baseline LDL-C ≥ 1.8 mmol/L, adding evolocumab to optimized statin therapy with or without ezetimibe is associated with an incremental cost per quality-adjusted life year (QALY) gained of $66,453 CAD. Furthermore, for every 100 patients treated with evolocumab for lifetime, adding evolocumab to optimized LLT will prevent approximately 52 cardiovascular (CV) events, of which seven would be fatal. The results are generally robust using univariate and simultaneous variation in model input parameters. Scenario analyses for patient populations as per the CCS guidelines suggest that evolocumab added to optimized LLT may be considered cost-effective, given an incremental cost-effectiveness ratio (ICER) threshold of CAD$100,000 per QALY gained. Limitations associated with this analysis should be interpreted in the context of data and modeling assumptions used. Conclusion Overall, this analysis supports reimbursement of evolocumab by payers in patients with ASCVD who cannot reach LDL-C thresholds despite optimized LLT to reduce unnecessary fatal and non-fatal CV events. Supplementary Information The online version contains supplementary material available at 10.1007/s12325-022-02130-4.

The relative efficacy and safety of dabigatran etexilate and warfarin have been evaluated in two head-to-head, phase III, treatment of acute venous thromboembolism (VTE) trials, and one extended prophylaxis trial, in patients with high risk of recurrent VTE. Dabigatran etexilate demonstrated similar efficacy to warfarin, and was associated with a reduced risk of major or clinically relevant bleeds. Based on results of these trials, and real-life disease prognosis following discontinuation of anticoagulation treatment, we evaluated the cost-utility of dabigatran etexilate compared with warfarin in six months anticoagulation, and in extended, up to 24 months anticoagulation, in patients with acute VTE, acute deep-vein thrombosis (DVT) or acute, symptomatic, pulmonary embolism (PE). Costs were analysed from the perspective of the National Health Services (NHS) and Public Social Services (PSS) in England and Wales. Outcomes were quantified in quality-adjusted life years (QALY). The estimated incremental, lifetime cost/QALY gain following acute, symptomatic VTE (DVT or PE) was £1,252/QALY when dabigatran etexilate or warfarin were administered for up to six months treatment. In treatment of acute, symptomatic PE and in DVT respective ratios were £1,767/QALY and £1,075/QALY. In extended, up to 24 months anticoagulation, dabigatran etexilate projected costs/QALY of £8,242/QALY, when compared with warfarin. Results obtained herein were robust across a number of sensitivity analyses and suggest dabigatran etexilate to be a cost-effective alternative to current standard of care when evaluated in six months treatment and in extended anticoagulation following acute VTE (DVT and/or PE).

Background Proprotein convertase subtilisin/kexin type 9 inhibitors, such as evolocumab, are cholesterol-lowering drugs effective in lowering lipid levels in high-risk patients with primary hypercholesterolemia or mixed dyslipidemia. Objective This study assessed the cost effectiveness of evolocumab in combination with lipid-lowering therapies (LLTs) compared with LLTs alone, from a public healthcare perspective in the Kingdom of Saudi Arabia (KSA). Methods A Markov cohort state transition model was used, incorporating efficacy estimates from the FOURIER clinical trial and baseline cardiovascular event rates observed in clinical practice. Other model inputs were extracted from the literature and Saudi sources. Results In patients with clinically evident atherosclerotic cardiovascular disease and baseline low-density lipoprotein cholesterol ≥ 70 or ≥ 100 mg/dL, adding evolocumab to a maximally tolerated statin, with or without ezetimibe, was associated with incremental cost-effectiveness ratios (ICERs) of Saudi Arabian riyal (SAR) 109,274 ($US60,708) per quality-adjusted lifeyear (QALY) gained and SAR75,163 ($US41,757) per QALY gained, respectively. The ICER was SAR22,391 ($US12,440) per QALY gained in patients with heterozygous familial hypercholesterolemia. Sensitivity analysis results were robust to changes in model parameters and fell below the willingness-to-pay threshold of up to three times gross domestic product per capita in 2019 (SAR264,813 [$US147,118]). Conclusion Evolocumab can be considered a cost-effective treatment option for patients with atherosclerotic cardiovascular disease or heterozygous familial hypercholesterolemia in the KSA.

A489cost-effective over rivaroxaban. ConClusions: In patients treated for acute pulmonary embolism, dabigatran is a cost-effective alternative compared with both warfarin and rivaroxaban.