Health and Economic Evaluation of Sacubitril-Valsartan for Heart Failure Management.

Importance: The US Food and Drug Administration expanded labeling of sacubitril-valsartan from the treatment of patients with chronic heart failure (HF) with reduced ejection fraction (EF) to all patients with HF, noting the greatest benefits in those with below-normal EF. However, the upper bound of below normal is not clearly defined, and value determinations across a broader EF range are unknown. Objective: To estimate the cost-effectiveness of sacubitril-valsartan vs renin-angiotensin system inhibitors (RASis) across various upper-level cutoffs of EF. Design, Setting, and Participants: This economic evaluation included participant-level data from the PARADIGM-HF (Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure) and the PARAGON-HF (Prospective Comparison of ARNi with ARB Global Outcomes in HF With Preserved Ejection Fraction) trials. PARADIGM-HF was conducted between 2009 and 2014, PARAGON-HF was conducted between 2014 and 2019, and this analysis was conducted between 2021 and 2023. Main Outcomes and Measures: A 5-state Markov model used risk reductions for all-cause mortality and HF hospitalization from PARADIGM-HF and PARAGON-HF. Quality-of-life differences were estimated from EuroQol-5D scores. Hospitalization and medication costs were obtained from published national sources; the wholesale acquisition cost of sacubitril-valsartan was $7092 per year. Risk estimates and treatment effects were generated in consecutive 5% EF increments up to 60% and applied to an EF distribution of US patients with HF from the Get With the Guidelines-Heart Failure registry. The base case included a lifetime horizon from a health care sector perspective. Incremental cost-effectiveness ratios (ICERs) were estimated at EFs of 60% or less (base case) and at various upper-level EF cutoffs. Results: Among 13 264 total patients whose data were analyzed, for those with EFs of 60% or less, sacubitril-valsartan was projected to add 0.53 quality-adjusted life-years (QALYs) at an incremental lifetime cost of $40 892 compared with RASi, yielding an ICER of $76 852 per QALY. In a probabilistic sensitivity analysis, 95% of the values of the ICER occurred between $71 516 and $82 970 per QALY. Among patients with chronic HF and an EF of 60% or less, treatment with sacubitril-valsartan vs RASis would be at least of economic intermediate value (ICER <$180 000 per QALY) at a sacubitril-valsartan cost of $10 242 or less per year, of high economic value (ICER <$60 000 per QALY) at a cost of $3673 or less per year, and cost-saving at a cost of $338 or less per year. The ICERs were $67 331 per QALY, $59 614 per QALY, and $56 786 per QALY at EFs of 55% or less, 50% or less, and 45% or less, respectively. Treatment with sacubitril-valsartan in only those with EFs of 45% or greater (up to ≤60%) yielded an ICER of $127 172 per QALY gained; treatment was more cost-effective in those at the lower end of this range (ICER of $100 388 per QALY gained for those with EFs of 45%-55%; ICER of $84 291 per QALY gained for those with EFs of 45%-50%). Conclusions and Relevance: Cost-effectiveness modeling provided an ICER for treatment with sacubitril-valsartan vs RASis consistent with high economic value for patients with reduced and mildly reduced EFs (≤50%) and at least intermediate value at the current undiscounted wholesale acquisition cost price at an EF of 60% or less. Treatment was more cost-effective at lower EF ranges. These findings may have implications for coverage decisions and value assessments in contemporary clinical practice guidelines.

Heart Failure and Shared Decision-Making: Patients Open to Medication-Related Cost Discussions.

BACKGROUND: Discussions of medication costs between patients and clinicians are infrequent and often suboptimal. In the context of recently introduced drugs that are effective but expensive, patients with heart failure with reduced ejection fraction provide an ideal population to understand the perspectives of patients with chronic illness on medication cost and cost discussions. METHODS: To explore patients' perspectives on discussing out-of-pocket medication costs with clinicians, 49 adults, aged 44 to 70 years, with heart failure with reduced ejection fraction were recruited from outpatient heart failure clinics. Descriptive qualitative analysis was performed on open-ended text data. RESULTS: Participants who had prior medication-related cost discussions described their experience as generally positive, but about half of the participants had never had a cost discussion with their clinician. Most participants were open to cost discussions with clinicians and preferred that the clinician initiate discussions regarding medication cost. Importantly, these preferences held constant across reported levels of financial burden. CONCLUSIONS: These data suggest a substantial willingness on the part of patients with heart failure with reduced ejection fraction to incorporate cost discussions into their care and identify important aspects of these discussions for clinicians to consider when engaging in conversations where cost is relevant. Improving understanding about how to integrate patient preferences regarding cost discussions into clinical encounters is an important priority for advancing patient-centered care.

Cost-effectiveness of Sacubitril-Valsartan in Hospitalized Patients Who Have Heart Failure With Reduced Ejection Fraction.

Importance: Sacubitril-valsartan use reduces mortality and hospitalizations compared with enalapril among patients with chronic heart failure with reduced ejection fraction (HFrEF); however, the cost-effectiveness of these treatments when initiated during hospitalization for HF is unknown. Objective: To estimate the cost-effectiveness of inpatient initiation of sacubitril-valsartan vs enalapril compared with no initiation or posthospitalization initiation of sacubitril-valsartan among stabilized patients with HFrEF. Design, Setting, and Participants: This economic evaluation included data on US patients with HFrEF who were eligible for sacubitril-valsartan treatment from December 8, 2009, to May 15, 2018. Main Outcomes and Measures: A 5-state Markov model with all-cause mortality, HF, and non-HF hospitalization probabilities was used. Quality of life was estimated using Euro-QoL EQ-5D scores. Hospitalization, long-term care, and medication costs for sacubitril-valsartan and enalapril were modeled with a discount rate of 3%. The base-case analysis included a lifetime horizon from a health care and societal perspective. Results: Modeled patients were a mean (SD) age of 63.8 (11.5) years. Inpatient treatment with sacubitril-valsartan ($5628 per year) was associated with 62 fewer HF-related admissions per 1000 patients compared with outpatient initiation or 116 fewer HF-related admissions compared with continuation of enalapril treatment. From a health care system perspective, initiation of sacubitril-valsartan during hospitalization saved $452 per year compared with continuing enalapril and $811 per year compared with initiation at 2 months after hospitalization and was associated with an incremental cost-effectiveness ratio of $21 532 per quality-adjusted life-year compared with continued enalapril treatment over a lifetime. From a societal perspective, inpatient initiation was estimated to save $460 per year per patient compared with no initiation of sacubitril-valsartan and $813 per year per patient compared with initiation after hospitalization. In a budget analysis, inpatient initiation of sacubitril-valsartan was estimated to save up to $449 per person for 1 year or $2550 per person over 5 years compared with continuation of enalapril. Conclusions and Relevance: The findings suggest that, for patients with HFrEF, initiation of sacubitril-valsartan during hospitalization may be associated with reduced hospitalizations, increased quality-adjusted life expectancy, and cost savings compared with no initiation or initiation after hospitalization.

Angiotensin Receptor Neprilysin Inhibitors-2019 Update.

An abundance of new data regarding the use of the novel drug compound sacubitril/valsartan in chronic heart failure (CHF) patients is published every year since the initial publication of the PARADIGM-HF study in 2014. This review summarises the most recent evidence (2019 and onwards) of sacubitril/valsartan in CHF patients as well as provides a critical appraisal of these data. New data are grouped in categories such as real-world data, randomised controlled trials, surrogate end-points, cost-effectiveness, use of sacubitril/valsartan as an anti-hypertensive treatment, effect on diuretic dosing and implementation of this novel compound in other populations. This review of recent literature identified important messages such as early initiation during index hospitalisation or immediately post-discharge, barriers against implementation of this novel treatment modality, analytical issues regarding measuring natriuretic peptides in patients under treatment and extrapolated use of sacubitril/valsartan in other than PARADIGM-HF populations. This update may serve as a very helpful evidence-based resource for practising clinicians, future research planning and health-related policy makers.

[Impact of stopping reimbursement of olmesartan for hypertensive patients in primary care]. / Impact du déremboursement de l'olmésartan chez les patients hypertendus en soins premiers.

AIMS OF STUDY: Since January 2017, olmesartan-based treatment are no longer reimbursed by French national health insurance. Indeed, enteropathy cases, potentially lethal, were described in relation to this medication. Objectives were to study the impact of stopping the reimbursement of olmesartan for hypertensive patients. PATIENTS AND METHOD: A descriptive retrospective study was performed with data from two primary care facilities in French occidental Normandy. To evaluate the blood pressure control, different blood pressure measurements were considered during the year before (period 1) and the year after (period 2) potential stopping olmesartan. A medico-economic analysis was also realized. RESULTS: From June 2015 to July 2017, 107 hypertensive patients treated by olmesartan were included. Among them, 47 patients (44%) had an antihypertensive monotherapy. olmesartan had been mainly switched by another sartan (75%, 80/107) including valsartan (59%, 47/80). Mean blood pressures during period 1 and period 2 were not statistically different. Moreover, 83% of patients were initially controlled with olmesartan and 81% after switching medication (P=0,86). The use of olmesartan generated an additional cost of 58% compared to the other drugs that replaced it during period 2. CONCLUSIONS: Stopping olmesartan reimbursement didn't seem to have a significant impact on blood pressure control of hypertensive patients while its cost is significant. In addition to potential serious side effects, olmesartan has not shown any improvement in cardiovascular morbi-mortality.

Cost-effectiveness of sacubitril/valsartan for the treatment of patients with heart failure with reduced ejection fraction in Portugal.

Objectives: This study assesses the cost-effectiveness of sacubitril/valsartan versus enalapril in patients with symptomatic heart failure with reduced ejection fraction (HFrEF).Methods: We used a previously developed Markov model calibrated with patient-level data from the PARADIGM-HF trial, adapted to the Portuguese setting. The model considers two health states (alive or dead) and uses regression analyzes to estimate hospitalizations and deaths over time. A panel of experts estimated resource consumption in the outpatient setting. To estimate resource consumption with hospitalizations, the National Health Service Diagnosis Related Groups database was used. Unit costs were based on national legislation, and on the Infomed database. The model considers a societal perspective, a time horizon of 30-years, and a 5% annual discount rate. Sensitivity analyses assessed the robustness of results.Results: Sacubitril/valsartan increases life expectancy by 0.5 life-years, corresponding to 0.4 incremental quality adjusted life-years (QALY) versus enalapril. The estimated incremental cost-effectiveness ratio (ICER) is 22,702€/QALY. Sensitivity analysis shows that results are robust, but sensitive to the parameter estimates of the cardiovascular survival curve.Conclusion: Sacubitril/valsartan is a cost-effective therapeutic option in the treatment of Portuguese patients with HFrEF and translate into significant health gains and increased life expectancy versus the current standard of care.

Economic evaluation of olmesartan/amlodipine fixed-dose combination for hypertension treatment in China.

Objectives: To evaluate the cost-effectiveness of olmesartan/amlodipine fixed-dose combination vs olmesartan and amlodipine free combination, amlodipine single drug, and valsartan/amlodipine fixed-dose combination in the treatment of hypertensive patients from payer perspective in China.Methods: A Markov model was constructed, which included five health states of hypertensive patients who are aged 35-84 years at baseline and free of cardiovascular disease. Clinical data were obtained from a network meta-analysis. Epidemiology data, adverse events (AEs), cost, and utility data were obtained from the literature. The cost associated with AEs was estimated based on the cost of same symptoms of hypertensive patients in an electric medical record database. The model projected quality-adjusted life years (QALYs) gained, total costs per patient in a 20-year time horizon, and incremental cost-effectiveness ratios. Probability sensitivity analyses (PSA) and one-way sensitivity analyses were conducted for the main parameters to test the robustness of the model.Results: Compared to olmesartan and amlodipine free combination, amlodipine, and valsartan/amlodipine fixed-dose combination, treatment with olmesartan/amlodipine fixed-dose combination led to fewer CVD events and deaths; resulted in an incremental cost of ¥-5,439 ($-791.36), ¥6,530 ($950.09), and ¥-1,019 ($-148.26) and gained additional QALYs of 0.052, 0.094, and 0.037 per patient, respectively. Compared with olmesartan and amlodipine free combination and valsartan/amlodipine fixed-dose combination, olmesartan/amlodipine fixed-dose combination was dominant. Compared with amlodipine alone, the incremental cost-effectiveness ratios were below the WHO recommended cost-effectiveness threshold, indicating the olmesartan/amlodipine fixed-dose combination was a cost-effective option for hypertensive patients in China. The 10-years' time horizon scenario analysis showed similar results to the 20-years' time horizon. Probabilistic sensitivity analysis and one-way sensitivity analyses showed the robustness of the model results.Conclusions: Olmesartan/amlodipine fixed-dose combination confers better health outcomes and costs less compared with olmesartan and amlodipine free combination and valsartan/amlodipine fixed-dose combination, and is cost-effective compared to amlodipine for hypertension treatment in China.

Contemporary Patterns of Medicare and Medicaid Utilization and Associated Spending on Sacubitril/Valsartan and Ivabradine in Heart Failure.

Importance: In 2015, the US Food and Drug Administration approved 2 new medications for treatment of heart failure with reduced ejection fraction, sacubitril/valsartan and ivabradine. However, few national data are available examining their contemporary use and associated costs. Objective: To evaluate national patterns of use of sacubitril/valsartan and ivabradine and associated therapeutic spending in Medicare Part D and Medicaid. Design, Setting, and Participants: In this US nationwide claims-based study, we analyzed data from the Medicare Part D Prescription Drug Event and Medicaid Utilization and Spending data sets to compare national patterns of use of sacubitril/valsartan and ivabradine between 2016 and 2017. Main Outcomes and Measures: Changes in total spending, per-beneficiary/claim spending, number of beneficiaries, and number of claims between 2016 and 2017 for sacubitril/valsartan and ivabradine. Results: The number of Medicare beneficiaries prescribed sacubitril/valsartan increased from 35 423 to 90 606 (156% increase from 2016 to 2017). Medicare beneficiaries prescribed ivabradine increased from 15 856 to 23 213 (46% increase). In 2017, Medicare Part D spent $227 million and $7.3 million on sacubitril/valsartan and ivabradine, respectively. This represented increases of 241% and 59% compared with 2016 spending, respectively. The annual Medicare per-beneficiary spending on sacubitril/valsartan and ivabradine was $2512 and $2400. Parallel trends in use patterns and spending were observed among Medicaid beneficiaries. Conclusions and Relevance: Although initial experiences suggested slow uptake after regulatory approval, these national data demonstrate an increase in use of sacubitril/valsartan and, to a lesser degree, ivabradine in the United States. Current annual per-beneficiary expenditures remain less than spending thresholds that have been reported to be cost-effective. Ongoing efforts are needed to promote high-value care while improving affordability and access to established and emerging heart failure therapies.

Cost-Effectiveness of Sacubitril/Valsartan in Germany: An Application of the Efficiency Frontier.

BACKGROUND: To assess the cost-effectiveness of new treatments in Germany, the efficiency frontier (EF) method has been developed. We compared the cost-effectiveness analysis using international standards and the German methodology, using the heart failure drug sacubitril/valsartan as an example. METHODS: A previously developed Markov model was adapted to include 4 treatment options: no treatment, enalapril, candesartan, and sacubitril/valsartan. The internationally used incremental cost-effectiveness ratio (ICER) was calculated, as well as cost-effectiveness acceptability curves. Additionally, EFs, net monetary benefits (NMBs), and price-acceptability curves were created according to German guidelines. All analyses were performed from the perspective of the German Statutory Health Insurance. RESULTS: The base-case ICER for sacubitril/valsartan compared to enalapril is €19 300/quality-adjusted life-year. On the cost-effectiveness acceptability curve, sacubitril/valsartan is most likely to be cost-effective, out of all included comparators, from a hypothetical willingness-to-pay threshold of €18 250/quality-adjusted life-year onward. No EF could be constructed for the base case. Taking the uncertainty of the input parameters into account for the probabilistic sensitivity analysis, a NMB of around -€14 000 was calculated, depending on the outcome considered, with the NMB being zero at a daily price for sacubitril/valsartan ranging from €1.52 to €1.67. CONCLUSION: We calculated an ICER for Germany, comparable to previously published cost-effectiveness analyses for Europe, which widely concluded sacubitril/valsartan to be cost-effective. Using the German EF approach, a considerable discount needs to be applied before sacubitril/valsartan can be considered cost-effective.

Cost-Utility Analysis of Sacubitril/Valsartan Use Compared With Standard Care in Chronic Heart Failure Patients With Reduced Ejection Fraction in South Korea.

PURPOSE: Sacubitril/valsartan, the first-in-class angiotensin receptor neprilysin inhibitor (ARNI), is a possible treatment option for chronic heart failure patients with reduced ejection fraction (HFrEF). The aim of this study was to estimate the cost-effectiveness of sacubitril/valsartan use in South Korea for treating patients with HFrEF compared with that of enalapril, an angiotensin-converting enzyme inhibitor, and with angiotensin receptor blockers (ARBs). METHODS: A Markov model was designed to estimate the lifetime cost-effectiveness of treatment for patients with HFrEF. Cohorts in the alive-state incurred a monthly risk of hospitalization because of deteriorated HF, adverse events (AEs), or death. Transition probabilities of sacubitril/valsartan and enalapril were estimated by using data from the PARADIGM-HF (Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure) trial. The effectiveness of ARBs (eg, reduction in mortality and hospitalization rates) was assumed to be identical to that of enalapril, according to the results of the meta-analysis. However, there was no comparative evidence for AEs. We therefore conducted a Bayesian network meta-analysis and adjusted the incidence rate of AEs for ARBs. The utility for estimating quality-adjusted life years (QALYs) was elicited by the survey of the general South Korean population by using EuroQol-5 dimensions. We calculated the medical costs, including medication, monitoring, hospitalization, AEs, and terminal care, from the health care sector perspective. Costs and effectiveness were discounted by 5%. One-way sensitivity analyses and a probabilistic sensitivity analysis were conducted to determine the model robustness. FINDINGS: The total cost per patient for sacubitril/valsartan and enalapril was $25,832 and $18,295, respectively. Sacubitril/valsartan was associated with an ∼8- month longer life expectancy compared with enalapril and a QALY gain of 0.59. As a result, the incremental cost-effectiveness ratio for sacubitril/valsartan versus enalapril was $12,722 per QALY. The incremental cost-effectiveness ratio of sacubitril/valsartan versus ARB was $11,970 with an incurred cost of $18,741 for the ARB group. The main results and those of various sensitivity analyses were lower than a threshold of $20,000. IMPLICATIONS: From a health care sector perspective, sacubitril/valsartan is a cost-effective treatment for HFrEF compared with enalapril and ARBs. This finding could be helpful for cardiologists or decision makers in reaching cost-effective choices regarding the treatment selection process.

The cost implication of primary prevention in the HOPE 3 trial.

AIMS: The Heart Outcomes Prevention Evaluation-3 (HOPE-3) found that rosuvastatin alone or with candesartan and hydrochlorothiazide (HCT) (in a subgroup with hypertension) significantly lowered cardiovascular events compared with placebo in 12 705 individuals from 21 countries at intermediate risk and without cardiovascular disease. We assessed the costs implications of implementation in primary prevention in countries at different economic levels. METHODS AND RESULTS: Hospitalizations, procedures, study and non-study medications were documented. We applied country-specific costs to the healthcare resources consumed for each patient. We calculated the average cost per patient in US dollars for the duration of the study (5.6 years). Sensitivity analyses were also performed with cheapest equivalent substitutes. The combination of rosuvastatin with candesartan/HCT reduced total costs and was a cost-saving strategy in United States, Canada, Europe, and Australia. In contrast, the treatments were more expensive in developing countries even when cheapest equivalent substitutes were used. After adjustment for gross domestic product (GDP), the costs of cheapest equivalent substitutes in proportion to the health care costs were higher in developing countries in comparison to developed countries. CONCLUSION: Rosuvastatin and candesartan/HCT in primary prevention is a cost-saving approach in developed countries, but not in developing countries as both drugs and their cheapest equivalent substitutes are relatively more expensive despite adjustment by GDP. Reductions in costs of these drugs in developing countries are essential to make statins and blood pressure lowering drugs affordable and ensure their use. CLINICAL TRIAL REGISTRATION: HOPE-3 ClinicalTrials.gov number, NCT00468923.

The impact of generics and generic reference pricing on candesartan and rosuvastatin utilisation, price and expenditure in South Africa.

Background In the South African private sector context, generically similar products are grouped together and the reimbursement rate is set at the average price of the generically equivalent products. Very little evidence exists in low and middle-income countries with regards to the impact of this policy over time. Objectives To determine the impact of the introduction of generics and generic reference pricing on candesartan and rosuvastatin in the South African private health care sector in terms of medicine utilisation, medicine price and medicine expenditure. Setting South African private health sector. Method Medicine claims for candesartan and rosuvastatin was obtained from a Pharmacy Benefit Manager in South Africa. The claims covered a 48-month period from January 2012 to December 2015 and provided a pre- and post-reference price period for analysis. Medicine utilisation was measured as the number of Defined Daily Doses dispensed per 100,000 beneficiaries. Medicine price and expenditure was calculated as the average per Defined Daily Dose. Main outcome measure Medicine utilisation, price and expenditure. Results Candesartan experienced an average 7.0% year-on-year decline in utilisation and rosuvastatin a 5.0% increase. Medicine expenditure reduced by an additional 34.6% and 20.9% for candesartan and rosuvastatin respectively. The total savings was 54.8% for candesartan and 31.9% for rosuvastatin. Conclusion The introduction of generics and generic reference pricing did not have an impact on medicine utilisation, but reduced the price and expenditure of both candesartan and rosuvastatin.

Discussing Out-of-Pocket Costs With Patients: Shared Decision Making for Sacubitril-Valsartan in Heart Failure.

Background "Financial toxicity" is a concern for patients, but little is known about how patients consider out-of-pocket cost in decisions. Sacubitril-valsartan provides a contemporary scenario to understand financial toxicity. It is guideline recommended for heart failure with reduced ejection fraction, yet out-of-pocket costs can be considerable. Methods and Results Structured interviews were conducted with 49 patients with heart failure with reduced ejection fraction at heart failure clinics and inpatient services. Patient opinions of the drug and its value were solicited after description of benefits using graphical displays. Descriptive quantitative analysis of closed-ended responses was conducted, and qualitative descriptive analysis of text data was performed. Of participants, 92% (45/49) said that they would definitely or probably switch to sacubitril-valsartan if their physician recommended it and out-of-pocket cost was $5 more per month than their current medication. Only 43% (21/49) would do so if out-of-pocket cost was $100 more per month ( P<0.001). At least 40% across all income categories would be unlikely to take sacubitril-valsartan at $100 more per month. Participants exhibited heterogeneous approaches to cost in decision making and varied on their use and interpretation of probabilistic information. Few (20%) participants stated physicians had initiated a conversation about cost in the past year. Conclusions Out-of-pocket cost variation reflective of contemporary cost sharing substantially influenced stated willingness to take sacubitril-valsartan, a guideline-recommended therapy with mortality benefit. These findings suggest a need for cost transparency to promote shared decision making. They also demonstrate the complexity of cost discussion and need to study how to incorporate out-of-pocket cost into clinical decisions.

Sacubitril/valsartan or an implantable cardioverter-defibrillator in heart failure with reduced ejection fraction patients: a cost-effectiveness analysis.

AIMS: The availability of novel drugs might affect the modern interplay between pharmacological and device therapy of heart failure with reduced ejection fraction (HFrEF). The aim of this study was to assess the cost-effectiveness of sacubitril/valsartan as compared with an implantable cardioverter-defibrillator (ICD) on top of optimal medical therapy in patients with HFrEF. METHODS: Data from 2000 adults with demographic and clinical characteristics similar to those in the PARADIGM-HF were derived as inputs for a four-state Markov model simulated HFrEF. Probabilities of all-cause mortality, heart failure hospitalization and ICD-related complications along with quality of life data and costs, discounted at 3%, from an Italian healthcare payer perspective were projected over a 10-year time horizon. Sensitivity analyses on key inputs were performed. RESULTS: According to the model, sacubitril/valsartan would lead to 5.85 life years saved, whilst reducing by more than 20% the risk of heart failure hospitalizations for 1000 patients with HFrEF over 10 years. Estimated incremental costs with sacubitril/valsartan were -&OV0556;13 302 associated with incremental 0.14 quality-adjusted life years gained, yielding an incremental cost-effectiveness ratio of -&OV0556;98 500 per quality-adjusted life year gained for the base-case consistent with a dominant, cost-saving and clinically superior treatment strategy. Sacubitril/valsartan was dominant in more than 80% of the scenarios explored with sensitivity analyses. CONCLUSION: The findings of this model suggest that in patients with HFrEF sacubitril/valsartan would be cost-effective by increasing survival at lower costs compared with an ICD. Sensitivity analyses confirmed the cost-effectiveness of sacubitril/valsartan that remained dominant across most of the ranges of the variables tested.

Sacubitril/Valsartan (LCZ696): A Novel Treatment for Heart Failure and its Estimated Cost Effectiveness, Budget Impact, and Disease Burden Reduction in Germany.

BACKGROUND: Heart failure affects over 1 million people in Germany and contributes to morbidity, mortality, and high healthcare costs. A recent large randomized controlled trial compared the novel compound sacubitril/valsartan (LCZ696) with the angiotensin-converting enzyme (ACE) inhibitor enalapril and found a 16% reduction in mortality hazard. In Germany, sacubitril/valsartan was launched at the beginning of 2016. OBJECTIVE: The purpose of this study was to conduct a post hoc analysis of the cost effectiveness, budget impact, and disease burden reduction of sacubitril/valsartan compared with ACE inhibitors for patients with heart failure from the perspective of the German social health insurance (SHI), based on the results of this trial. METHODS: A Markov (cohort) state transition model was constructed to simulate treatment over a remaining lifetime. Based on the Markov model, a dynamic population model was developed that projects the incidence, prevalence, mortality, and healthcare costs of heart failure in the SHI population from 2017 to 2060. The population model follows prevalent and incident cohorts over time. Each year a new cohort is added, while the existing cohorts age by 1 year or die. To test for sensitivity of results, a Monte Carlo simulation was run. RESULTS: Based on the price negotiated between manufacturer and representatives of the SHI, the base-case incremental cost-effectiveness ratio (ICER) of sacubitril/valsartan versus ACE inhibitors is €23,401 per life-year gained (in 2018 Euros). At a price of zero, the cost-effectiveness ratio is already €9594 per life-year gained due to high background costs of heart failure. Annual budget impact and reduction of disease burden reach a maximum at 4-8 years after launch (€221 million and 2.9%, respectively, in the base case). CONCLUSIONS: The ICER of sacubitril/valsartan is projected to be at or below the level of other accepted interventions for the treatment of asymptomatic to severe heart failure in Germany. Projected budget impact leads to an increase in SHI expenditures by < 0.04% per year.

Cost-Effectiveness Analysis of Sacubitril-Valsartan Compared with Enalapril in Patients with Heart Failure with Reduced Ejection Fraction in Thailand.

BACKGROUND: Sacubitril-valsartan is a new medication that has recently been recommended as a replacement for enalapril in the treatment of patients with heart failure with reduced ejection fraction (HFrEF). OBJECTIVE: This study aimed to determine the cost effectiveness of sacubitril-valsartan compared with enalapril. METHODS: An analytical decision model was developed to estimate the long-term costs and outcomes from a healthcare perspective. Clinical inputs were mostly derived from the PARADIGM-HF study. Enalapril-related costs, risk of non-cardiovascular death, and all-cause readmission rate were based on data from Thailand. The costs and outcomes were discounted at 3% annually. The incremental cost-effectiveness ratio (ICER) was calculated and presented for the year 2017. A series of sensitivity analyses were also performed. RESULTS: For the base-case, the increased cost (144,146 vs. 16,048 Thai baht [THB]) of sacubitril-valsartan was associated with gains in both life-years (9.214 vs. 8.367 years) and quality-adjusted life-years (QALYs) (7.698 vs. 6.909) compared with enalapril, yielding an ICER of 162,276 THB/QALY ($US4857.11/QALY). This ICER is not considered to be cost effective at the willingness-to-pay (WTP) level of 160,000 THB/QALY. The risk of cardiovascular death and costs of both sacubitril-valsartan and hospitalization influenced the ICER. At a WTP of 160,000 THB/QALY, sacubitril-valsartan had a 48% probability of being a cost-effective treatment. CONCLUSIONS: At its current price in Thailand, sacubitril-valsartan may not represent good value for the nations's limited healthcare resources. The cost of sacubitril-valsartan needs to reduce by approximately 2% to yield an ICER below the threshold.

The repercussion of stopping reimbursement of olmésartan on antihypertensive drugs prescription and blood pressure control of treated hypertensive patients in France.

OBJECTIVE: Since January 2017, olmesartan-based treatments are no longer reimbursed by French health insurance. Health authorities have recommended switch to one of the "many effective, better tolerated and reimbursed alternatives". The objective of this study was to evaluate the consequences on the prescription of antihypertensive drugs in France and to evaluate the blood pressure control of treated hypertensive patients after the switch from olmesartan to another Angiotensin receptor blocker (ARB). METHODS: To evaluate antihypertensive prescriptions, the French League Against Hypertension Survey (FLAHS) was conducted in 2007, 2012 and 2017 by self-questionnaire sent by mail to a representative panel of the population living in metropolitan France aged 35 years and over. Antihypertensive treatments were grouped by pharmacological class. To evaluate blood pressure control in hypertensive patients treated with olmesartan alone or in combination, 3 home blood pressure monitoring (HBPM) were performed. The first and the second were performed without modification of the dose of olmesartan. The third was performed 1 month after the switch to another ARB. RESULTS: Antihypertensive prescriptions changed between 2007 and 2017. Beta-blockers decreased between 2007 and 2012 and then increased slightly. Between 2012 and 2017, ARB and diuretics decreased and ACE inhibitors (ACE-I) and calcium antagonist (CA) drugs increased. Blood pressure control was assessed in 82 hypertensive patients aged 63±11 years treated with olmesartan. The difference in SBP/DBP between the first 2 self-measurements was -0.96/-0.83mmHg. After therapy switch, the 3rd self-measurement showed an increase in SBP/DBP of 3.4/1.2mmHg. In the subgroup of olmesartan-treated controlled hypertensive patients, the switch to another ARB lead to uncontrolled hypertension for 20% of patients with a 12.1mmHg increase in SBP. CONCLUSION: With the halt of reimbursement of olmesartan, there was a decrease in the prescription of ARB in France. When olmersartan was replaced by another ARB, a worse blood pressure control was observed in treated hypertensive patients. The cessation of the reimbursement of olmesartan has had consequences on the treatment of hypertension in France.

Cost-Effectiveness Analysis of Sacubitril/Valsartan for the Treatment of Heart Failure with Reduced Ejection Fraction in the United States.

OBJECTIVE: Sacubitril/valsartan (SAC/VAL) has been shown to reduce mortality and hospitalization in patients with heart failure with reduced ejection fraction (HFrEF) compared with enalapril but at a substantially higher cost. This study evaluates the cost-effectiveness of SAC/VAL versus enalapril in patients with HFrEF over a 5-year time horizon from the U.S. payer perspective. METHODS: A cohort-based Markov model was developed to compare costs and quality-adjusted life years (QALYs) between SAC/VAL and enalapril in patients with HFrEF over a 5-year time horizon. Markov states included New York Heart Association (NYHA) class (II-IV) and death. Treatment discontinuation, HF-related hospitalizations, and NYHA class progression were modeled as transition states based on data from the PARADIGM trial. Other probabilities, costs, and utilities were obtained from published literature and public databases. RESULTS: In the base case analysis, SAC/VAL cost more than enalapril ($81,943 vs $67,287) and was more effective (2.647 QALYs vs 2.546 QALYs), resulting in an incremental cost-effectiveness ratio of $143,891/QALY gained. At a willingness to pay (WTP) of $100,000/QALY, SAC/VAL was cost-effective up to a cost of $298/month. Results were most sensitive to SAC/VAL cost, SAC/VAL mortality benefit, and NYHA progression probability. SAC/VAL had a 10% and 52% probability of being cost-effective at WTP thresholds of $100,000/QALY and $150,000/QALY, respectively. CONCLUSIONS: SAC/VAL is associated with clinical benefit and may be cost-effective compared with the current standard of care over realistic treatment durations from the payer perspective. Results of this analysis can inform discussions on the value and position of SAC/VAL in the current market.

Adoption of Sacubitril/Valsartan for the Management of Patients With Heart Failure.

BACKGROUND: The US Food and Drug Administration approved the use of sacubitril/valsartan in patients with heart failure with reduced ejection fraction in July 2015. We aimed to assess the adoption and prescription drug costs of sacubitril/valsartan in its first 18 months after Food and Drug Administration approval. METHODS AND RESULTS: Using a large US insurance database, we identified privately insured and Medicare Advantage beneficiaries who filled a first prescription for sacubitril/valsartan between July 1, 2015, and December 31, 2016. We compared them to patients treated with an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker. Outcomes included adoption, prescription drug costs, and 180-day adherence, defined as a proportion of days covered ≥80%. A total of 2244 patients initiated sacubitril/valsartan. Although the number of users increased over time, the proportion of heart failure with reduced ejection fraction patients taking sacubitril/valsartan remained low (<3%). Patients prescribed sacubitril/valsartan were younger, more often male, with less comorbidity than those taking an angiotensin-converting enzyme inhibitor/angiotensin receptor blocker. Although a majority of prescription costs were covered by the health plan (mean, $328.37; median, $362.44 per 30-day prescription), out-of-pocket costs were still high (mean, $71.16; median, $40.27). By comparison, median out-of-pocket costs were $2 to $3 for lisinopril, losartan, carvedilol, and spironolactone. Overall, 59.1% of patients were adherent to sacubitril/valsartan. Refill patterns suggested that nearly half of nonadherent patients discontinued sacubitril/valsartan within 180 days of starting. CONCLUSIONS: Adoption of sacubitril/valsartan after Food and Drug Administration approval has been slow and may be associated with the high cost.