[Clinical and economic analysis of the use of dapagliflozin in patients with chronic heart failure with reduced left ventricular ejection fraction in various subgroups of standard therapy in the Russian Federation].

AIM: To evaluate the clinical and economic effectiveness of dapagliflozin in patients with chronic heart failure (CHF) with reduced left ventricular ejection fraction (HFrEF) in the Russian Federation in various subgroups of standard therapy for CHF. MATERIALS AND METHODS: A clinical and economic analysis of the use of the drug dapagliflozin in addition to standard therapy was carried out in comparison with standard therapy in various subgroups of standard therapy for HFrEF using a modeling method. Cost calculations were carried out in a mathematical model adapted to the healthcare conditions of the Russian Federation by using Russian cost indicators and characteristics of the patient population. RESULTS: The present study demonstrates that the addition of dapagliflozin is beneficial in terms of clinical and cost-effectiveness, regardless of the initial regimen (angiotensin receptor-neprilysin inhibitors [ARNI] or angiotensin-converting enzyme inhibitors [ACEi]/angiotensin II receptor blockers [ARB]) of standard drug therapy for HFrEF and in all cases leads to an increase in life expectancy, a decrease in the number of hospitalizations and emergency visits due to CHF, as well as cardiovascular mortality. The obtained values of added value per additional year of life in all cases are significantly lower than the willingness-to-pay threshold, which indicates the clinical and economic effectiveness of the strategy of prescribing dapagliflozin as part of standard therapy for patients with HFrEF. In the case of adding dapagliflozin the values of the additional cost of an added year of life in the 3 considered standard therapy options (ARNI or ACEi/ARB, only ACEi/ARB and only ARNI) were 291,256, 279,571 and 338,374 rubles respectively. Thus, the scenario of using dapagliflozin with standard therapy, which included only ACEi/ARB, is characterized by the lowest additional cost and has the best clinical and economic characteristics. At the same time the scenario of use with standard therapy, which included only ARNI, is characterized by the highest value of the additional value of the added year of life.

Cost-effectiveness of ace inhibitors versus ARBs in heart failure management.

BACKGROUND: Heart failure is a chronic condition that imposes a significant burden on healthcare systems worldwide. Effective management is crucial for improving patient outcomes and reducing costs. Angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) are widely used to manage heart failure by reducing cardiac strain and preventing disease progression. Despite their common use, ACE inhibitors and ARBs differ in mechanisms, cost, and potential side effects. ACE inhibitors have long been the standard treatment, while ARBs are often prescribed to patients intolerant to ACE inhibitors, particularly due to side effects like cough. Given these differences, evaluating the cost-effectiveness of these treatments is essential. This study compares the cost-effectiveness of ACE inhibitors and ARBs from a healthcare system perspective, considering both direct medical costs and health outcomes. METHODS: A cost-effectiveness analysis was conducted using a decision-analytic Markov model to simulate heart failure progression in a hypothetical cohort. Data inputs included clinical trial outcomes, real-world effectiveness data, direct medical costs (medications, hospitalizations, monitoring), and utility values for quality of life. The primary outcome measures were the cost per quality-adjusted life year gained and the incremental cost-effectiveness ratio. Sensitivity analyses tested the robustness of results, and subgroup analyses were conducted based on age and disease severity. RESULTS: The base-case analysis showed that ACE inhibitors were associated with lower overall costs and slightly higher quality-adjusted life years than ARBs. Sensitivity analyses revealed that variations in key parameters, such as transition probabilities, mortality rates, and healthcare expenses, had limited impact on the overall cost-effectiveness conclusions. Subgroup analyses indicated that ACE inhibitors and ARBs exhibited similar cost-effectiveness profiles for patients aged <65 and ≥65 years. However, among patients with severe heart failure, ARBs demonstrated a higher incremental cost-effectiveness ratio compared with ACE inhibitors, suggesting reduced cost-effectiveness in this subgroup. CONCLUSION: ACE inhibitors are likely a more cost-effective option for managing heart failure than ARBs, particularly from a healthcare system perspective. The findings underscore the importance of tailoring treatment decisions to individual patient factors, preferences, and clinical conditions, providing valuable insights for healthcare policy and practice, particularly regarding cost-effectiveness across patient subgroups.

Cost-effectiveness of single-pill and separate-pill administration of antihypertensive triple combination therapy: a population-based microsimulation study.

BACKGROUND: Single-pill combination (SPC) of three antihypertensive drugs has been shown to improve adherence to therapy compared with free combinations, but little is known about its long-term costs and health consequences. This study aimed to evaluate the lifetime cost-effectiveness profile of a three-drug SPC of an angiotensin-converting enzyme inhibitor, a calcium-channel blocker, and a diuretic vs the corresponding two-pill administration (a two-drug SPC plus a third drug separately) from the Italian payer perspective. METHODS: A cost-effectiveness analysis was conducted using multi-state semi-Markov modeling and microsimulation. Using the healthcare utilization database of the Lombardy Region (Italy), 30,172 and 65,817 patients aged ≥ 40 years who initiated SPC and two-pill combination, respectively, between 2015 and 2018 were identified. The observation period extended from the date of the first drug dispensation until death, emigration, or December 31, 2019. Disease and cost models were parametrized using the study cohort, and a lifetime microsimulation was applied to project costs and life expectancy for the compared strategies, assigning each of them to each cohort member. Costs and life-years gained were discounted by 3%. Probabilistic sensitivity analysis with 1,000 samples was performed to address parameter uncertainty. RESULTS: Compared with the two-pill combination, the SPC increased life expectancy by 0.86 years (95% confidence interval [CI] 0.61-1.14), with a mean cost differential of -€12 (95% CI -9,719-8,131), making it the dominant strategy (ICER = -14, 95% CI -€15,871-€7,113). The cost reduction associated with the SPC was primarily driven by savings in hospitalization costs, amounting to €1,850 (95% CI 17-7,813) and €2,027 (95% CI 19-8,603) for patients treated with the SPC and two-pill combination, respectively. Conversely, drug costs were higher for the SPC (€3,848, 95% CI 574-10,640 vs. €3,710, 95% CI 263-11,955). The cost-effectiveness profile did not significantly change according to age, sex, and clinical status. CONCLUSIONS: The SPC was projected to be cost-effective compared with the two-pill combination at almost all reasonable willingness-to-pay thresholds. As it is currently prescribed to only a few patients, the widespread use of this strategy could result in benefits for both patients and the healthcare system.

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.

Exposure to guideline-recommended drugs after a first acute myocardial infarction in older adults: does deprivation matter?

BACKGROUND: Inequities between guideline-recommended drugs (GRD) exposure and socioeconomic status might exist. The objective was to assess the association between a material and a social deprivation index and GRD exposure following a first acute myocardial infarction (AMI) in older adults in the province of Quebec. METHODS: We conducted a retrospective cohort study using the Quebec Integrated Chronic Disease Surveillance System. Elderly ≥66 years, hospitalized for a first AMI between January 1, 2006, and December 31, 2011 and covered by the public drug plan were identified. Exposure to GRD (i.e. simultaneous use of 1) antiplatelet, 2) beta-blocker, 3) lipid-lowering and 4) angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker drugs) was assessed 30 and 365 days following hospital discharge. Associations between deprivation index and GRD exposure were estimated with log-binomial regressions adjusting for potential confounders. RESULTS: Exposure to GRD was 52.2% and 48.0%, 30 and 365 days after hospital discharge, respectively. No statistically significant association was observed in multivariate analysis for both time points. Thirty days post hospital discharge, adjusted prevalence ratio of non-exposure to GRD was 0.98 (95% confidence interval [CI]: 0.95-1.02) for most materially deprived vs. least deprived and 1.04 (95% CI: 0.99-1.08) for most socially deprived vs. least deprived. Similar results were observed for 365 days. CONCLUSION: Exposure to GRD after a first urgent AMI among older adults insured by the public drug plan in the province of Quebec is relatively low. Reasons and risk groups for this low exposure should be studied to improve secondary prevention. However, results suggest equitable access to GRD, regardless of deprivation.

Budget impact analysis of increasing prescription of renin-angiotensin system inhibitors drugs to standard anti-hypertensive treatments in patients with diabetes and hypertension in a hypothetical cohort of Malaysian population.

INTRODUCTION: Renin-angiotensin system inhibitors (RAS) drugs have a proteinuria-reducing effect that could prevent the progression of kidney disease in diabetic patients. Our study aimed to assess the budget impact based on healthcare payer perspective of increasing uptake of RAS drugs into the current treatment mix of standard anti-hypertensive treatments to prevent progression of kidney disease in patient's comorbid with hypertension and diabetes. METHODS: A Markov model of a Malaysian hypothetical cohort aged ≥30 years (N = 14,589,900) was used to estimate the total and per-member-per-month (PMPM) costs of RAS uptake. This involved an incidence and prevalence rate of 9.0% and 10.53% of patients with diabetes and hypertension respectively. Transition probabilities of health stages and costs were adapted from published data. RESULTS: An increasing uptake of RAS drugs would incur a projected total treatment cost ranged from MYR 4.89 billion (PMPM of MYR 27.95) at Year 1 to MYR 16.26 billion (PMPM of MYR 92.89) at Year 5. This would represent a range of incremental costs between PMPM of MYR 0.20 at Year 1 and PMPM of MYR 1.62 at Year 5. Over the same period, the care costs showed a downward trend but drug acquisition costs were increasing. Sensitivity analyses showed the model was minimally affected by the changes in the input parameters. CONCLUSION: Mild impact to the overall healthcare budget has been reported with an increased utilization of RAS. The long-term positive health consequences of RAS treatment would reduce the cost of care in preventing deterioration of kidney function, thus offsetting the rising costs of purchasing RAS drugs. Optimizing and increasing use of RAS drugs would be considered an affordable and rational strategy to reduce the overall healthcare costs in Malaysia.

Impact of Optimal Medical Therapy at Discharge on One-year Direct Medical Costs in Patients with Acute Coronary Syndromes: A Retrospective, Observational Database Analysis in China.

PURPOSE: This study was conducted to examine the use of optimal medical therapy (OMT), consisting of an antiplatelet, a ß-blocker, an angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (ACEI/ARB), and a statin combined, after hospital discharge and its relationship with direct medical costs in patients with acute coronary syndromes (ACS) in Tianjin, China. METHODS: Data were obtained from the Tianjin Urban Employee Basic Medical Insurance database (2011-2015). Data from adult patients with ≥1 hospitalization for ACS between January 2012 and December 2014 were included. Medications including antiplatelets, ß-blockers, ACEIs/ARBs, and statins at discharge were recorded, with OMT defined as the use of all 4 indicated medications. Propensity-score matching was conducted to form matched OMT and non-OMT cohorts based on baseline differences. All-cause and ACS-related health care resource utilization and direct medical costs during a 12-month follow-up period were assessed and compared between cohorts. Generalized linear modeling was conducted to assess the association between OMT at discharge and direct medical costs. FINDINGS: A total of 22,041 patients were identified (mean age, 64.7 [10.7] years; 45.6% female), of whom 15.1% (3336) received OMT at discharge. The OMT cohort had fewer patients hospitalized for any cause during follow-up compared with the matched non-OMT cohort (38.1% vs 43.2%; P < 0.001), which was further associated with fewer hospitalizations (1.55 vs 1.64; P = 0.019) and shorter annualized length of stay (15.9 vs 17.2 d; P = 0.041). Despite higher costs of outpatient services (9958 vs 10,060 Chinese yuan [CNY] [P = 0.006]; adjusted difference, +456 CNY [P = 0.004]) (year-2014 1 USD = 6.20 CNY), the OMT cohort had significantly lower all-cause total costs (20,771 vs 22,877 CNY [P = 0.174]; adjusted difference, -2089 CNY [P = 0.006]), driven by lower costs of inpatient services (10,813 vs 12,817 CNY [P < 0.001]; adjusted difference, -2184 CNY [P = 0.001]). The difference in ACS-related total costs between the 2 cohorts was not statistically significant (8535 vs 9304 CNY [P = 0.128]; adjusted difference, -558 CNY [P = 0.214]). IMPLICATIONS: Receiving OMT at discharge was associated with fewer hospitalizations and lower all-cause direct medical costs in these patients with ACS in China. Strategies are needed to improve OMT prescribing rates at discharge, which would lead to better clinical prognosis and total cost-savings among patients with ACS in China.

Effectiveness of treatment of newly diagnosed hypertension in family medicine practices in South Croatia.

BACKGROUND: Uncontrolled blood pressure remains an urgent issue in clinical practice worldwide. This study aimed to compare the characteristics and effectiveness of hypertension control in family medicine pratice in the first treatment year, in relation to the geographical position, socio-economic standard, and access to medical services and public pharmacies in urban, rural and island environments (city of Split vs. Dalmatian Hinterland vs. islands in Southern Croatia). METHODS: A historical cohort study included 213 patients diagnosed from 2008 to 2014 with essential arterial hypertension (AH) and without related complications or diabetes mellitus. Each patient was followed up for 365 days from the visit when the diagnosis of hypertension was ascertained. Normotension was defined as arterial pressure < 140/90 mmHg. The annual cost of drugs prescribed for treating newly diagnosed hypertensive patient and the total price for defined daily dose per patient were also evaluated. RESULTS: More than half patients achieved normotension within a year from the initial diagnosis in all family medicine practices (57.3%), without significant differences among the three geographic regions (P = 0.981). Higher initial systolic blood pressure was a positive predictive prognostic factor on achieveing normotension (odds ratio (OR) 0.96, 95% confidence interval 0.95-0.98). ACE inhibitors were the most commonly prescribed antihypertensive agents in monotherapy (35.1%), as well as considering overall prescriptions (25.2%). Calcium channel blockers were the most commonly prescribed initial BP-lowering single agents in urban areas (28.6%), whereas angiotensin-converting enzyme inhibitors were more common in rural (28.0%) and island areas (22.7%) (P = 0.037). The median annual antihypertensive drug cost was 169.4 (95% CI 151.5-201.8) Croatian kunas and was similar across the study sites. CONCLUSION: Multiple antihypertensive drugs, prescribed in accordance with the guidelines, lead to similar pharmacological effects. Primary care physicians seem to be able to overcome potential interfering socio-economic factors and successfully achieve normotension in newly diagnosed patients with uncomplicated AH after 1 year of treatment.

Clinical and economic implications of therapeutic switching of angiotensin receptor blockers to angiotensin-converting enzyme inhibitors: a population-based study.

OBJECTIVE: To evaluate the clinical and cost impact of switching angiotensin receptor blockers (ARBs) to angiotensin-converting enzyme inhibitors (ACEIs) in patients with hypertension. METHODS: This study used the UK Clinical Practice Research Datalink, linking with the Hospital Episode Statistics (April 2006 to March 2012). Adults with hypertension (n = 470) were followed from the first ARB prescription date to the switching date (preswitching period); then from the switching date to the date when study ended, patient left the dataset or died (postswitching period). Patients were divided into ACEIs-combined (n = 369) and ACEIs-monotherapy (n = 101) groups by whether additional antihypertensive drugs were prescribed with ACEIs in the postswitching period. Proportion of days covered (PDC), clinical outcomes and costs were compared between the preswitching and postswitching periods using a multilevel regression. RESULTS: Overall, in the postswitching period, there was a significant increase in the proportion of nonadherence (PDC < 80%) (OR: 2.4; 95% CI: 1.6-3.7), but a significant reduction in mean SBP (mean difference: -2.3; 95 CI: -3.4 to 1.2 mmHg) and mean DBP (mean difference: -1.9; 95% CI: -2.6 to -1.2 mmHg). However, these results were only observed in the ACEIs-combined group. There was no postswitching significant difference in either the incidence of individual or composite hypertension-related complications (OR: 0.9; 95% CI: 0.4-2.0). There was a significant reduction in the overall annual medical cost per patient by £329 (95% CI: -534 to -205). CONCLUSION: Switching of ARBs to ACEIs monotherapy appeared to be clinically effective and a cost-saving strategy. The observed changes in the ACEIs-combined group are assumed to be related to factors other than the ARBs switching.

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.

Trends in Diabetes Treatment and Monitoring among Medicare Beneficiaries.

BACKGROUND: Diabetes is a costly and common condition, but little is known about recent trends in diabetes management among Medicare beneficiaries. OBJECTIVE: To evaluate the use of diabetes medications and testing supplies among Medicare beneficiaries. DESIGN/SETTING: Retrospective cohort analysis of Medicare claims from 2007 to 2014. PARTICIPANTS: Traditional Medicare beneficiaries with a diagnosis of diabetes in the current or any prior year. MAIN MEASURES: We analyzed choices of first diabetes medication for those new to medication and patterns of adding medications. We also examined the use of testing supplies, use of statins and ACE inhibitors/angiotensin receptor blockers, and spending. KEY RESULTS: Diagnosed diabetes increased from 28.7% to 30.2% of beneficiaries from 2007 to 2014. The use of metformin as the most commonly prescribed first medication increased from 50.2% in 2007 to 70.2% in 2014, whereas long-acting sulfonylureas decreased from 16.6% to 8.2%. The use of thiazolidinediones fell considerably, while the use of new diabetes medication classes increased. Among patients prescribed insulin, long-acting insulin as the first choice increased substantially, from 38.9% to 56.8%, but short-acting or combination regimens remained common, particularly among older or sicker beneficiaries. Prescriptions of testing supplies for more than once-daily testing were also common. The mean total cost of diabetes medications per patient increased over the period due to the increasing use of high-cost drugs, particularly by those patients with costs above the 90th percentile of spending, although the median costs decreased for both medications and testing supplies. CONCLUSIONS: The use of metformin and long-acting insulin have increased substantially among elderly Medicare patients with diabetes, but a substantial subgroup continues to receive costly and complex treatment regimens.

Cost Effectiveness of the Angiotensin Receptor Neprilysin Inhibitor Sacubitril/Valsartan for Patients with Chronic Heart Failure and Reduced Ejection Fraction in the Netherlands: A Country Adaptation Analysis Under the Former and Current Dutch Pharmacoeconomic Guidelines.

OBJECTIVES: To describe the adaptation of a global health economic model to determine whether treatment with the angiotensin receptor neprilysin inhibitor LCZ696 is cost effective compared with the angiotensin-converting enzyme inhibitor enalapril in adult patients with chronic heart failure with reduced left ventricular ejection fraction in the Netherlands; and to explore the effect of performing the cost-effectiveness analyses according to the new pharmacoeconomic Dutch guidelines (updated during the submission process of LCZ696), which require a value-of-information analysis and the inclusion of indirect medical costs of life-years gained. METHODS: We adapted a UK model to reflect the societal perspective in the Netherlands by including travel expenses, productivity loss, informal care costs, and indirect medical costs during the life-years gained and performed a preliminary value-of-information analysis. RESULTS: The incremental cost-effectiveness ratio obtained was €17,600 per quality-adjusted life-year (QALY) gained. This was robust to changes in most structural assumptions and across different subgroups of patients. Probability sensitivity analysis results showed that the probability that LCZ696 is cost-effective at a €50,000 per QALY threshold is 99.8%, with a population expected value of perfect information of €297,128. On including indirect medical costs of life-years gained, the incremental cost-effectiveness ratio was €26,491 per QALY gained, and LCZ696 was 99.46% cost effective at €50,000 per QALY, with a population expected value of perfect information of €2,849,647. CONCLUSIONS: LCZ696 is cost effective compared with enalapril under the former and current Dutch guidelines. However, the (monetary) consequences of making a wrong decision were considerably different in both scenarios.

Cost-effectiveness Analyses of Antihypertensive Medicines: A Systematic Review.

CONTEXT: Hypertension affects one third of the U.S. adult population. Although cost-effectiveness analyses of antihypertensive medicines have been published, a comprehensive systematic review across medicine classes is not available. EVIDENCE ACQUISITION: PubMed, Embase, Cochrane Library, and Health Technology Assessment were searched to identify original cost-effectiveness analyses published from 1990 through August 2016. Results were summarized by medicine class: angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), calcium channel blockers (CCBs), thiazide-type diuretics, ß-blockers, and others. Incremental cost-effectiveness ratios (ICERs) were adjusted to 2015 U.S. dollars. EVIDENCE SYNTHESIS: Among 76 studies reviewed, 14 compared medicines with no treatment, 16 compared medicines with conventional therapy, 29 compared between medicine classes, 13 compared within medicine class, and 11 compared combination therapies. All antihypertensives were cost effective compared with no treatment (ICER/quality-adjusted life year [QALY]=dominant-$19,945). ARBs were more cost effective than CCBs (ICER/QALY=dominant-$13,016) in nine comparisons, whereas CCBs were more cost effective than ARBs (ICER/QALY=dominant) in two comparisons. ARBs were more cost effective than ACEIs (ICER/QALY=dominant-$34,244) and ß-blockers (ICER/QALY=$1,498-$18,137) in all eight comparisons. CONCLUSIONS: All antihypertensives were cost effective compared with no treatment. ARBs appeared to be more cost effective than CCBs, ACEIs, and ß-blockers. However, these latter findings should be interpreted with caution because these findings are not robust due to the substantial variability across the studies, including study settings and analytic models, changes in the cost of generic medicines, and publication bias.

Early health technology assessments in pharmacogenomics: a case example in cardiovascular drugs.

AIM: To assess the required characteristics (cost, sensitivity and specificity) of a pharmacogenomic test for being a cost-effective prevention of angiotensin-converting enzyme inhibitors induced angioedema. Furthermore, we assessed the influence of only testing high-risk populations. MATERIALS & METHODS: A decision tree was used. RESULTS: With a willingness-to-pay threshold of €20,000 and €80,000 per quality adjusted life year, a 100% sensitive and specific test may have a maximum cost of €1.30 and €1.95, respectively. When only genotyping high-risk populations, the maximum test price would be €5.03 and €7.55, respectively. CONCLUSION: This theoretical pharmacogenomic test is only cost-effective at high specificity, high sensitivity and a low price. Only testing high-risk populations yields more realistic maximum test prices for cost-effectiveness of the intervention.

Cost-effectiveness of angiotensin-converting enzyme inhibitors versus angiotensin II receptor blockers as first-line treatment in autosomal dominant polycystic kidney disease.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is a rare kidney disorder impacting ∼1:2,500 individuals among the general US population. Hypertension is a significant predictor of ADPKD progression, and a risk factor for development of cardiovascular disease (CVD), the most common cause for mortality among ADPKD patients. Angiotensin-converting enzymes inhibitors (ACE-I) are widely used as first-line treatment in ADPKD for the management of hypertension. However, their cost-effectiveness relative to other hypertensive medications, such as angiotensin II receptor blockers (ARB), has never been assessed. OBJECTIVE: To determine if ARB are more cost-effective than ACE-Is as first-line treatment in ADPKD. METHODS: A Markov-state decision model was constructed for estimation of cost and outcome benefits in hypertensive ADPKD patients. Transition probabilities were extrapolated from a retrospective cohort study comparing chronic kidney disease (CKD) stage transitions in ADPKD patients. Annual pharmaceutical costs per average daily dose per CKD stage were extracted from a US healthcare claims database. Median total healthcare costs per CKD stage or transplant were extracted from the published literature. The time horizon was set to 30 years, with 1-year duration to cycle shift. A cost-effectiveness analysis was conducted to estimate the incremental cost-effectiveness ratio (ICER) of ACE-I vs ARB per additional year of prevented transplant and/or death. A one-way probabilistic sensitivity analysis was conducted, with 10% variation in probabilities and cost. RESULTS: Total annual healthcare costs accrued after 30 years among ADPKD patients taking ACE-Is was estimated to be $3,505,028.41, compared to ARB at $3,644,327.65. Life expectancy was increased by 1.39 years among patients taking ACE-I. Approximate 10-year survival in patients taking ACE-Is was 47% compared to ARB at 34%. CONCLUSIONS: ACE-I dominated ARB and displayed greater cost-effectiveness due to lower cost and increased capacity to prolong years of life without transplant or death among hypertensive ADPKD patients. This model strengthens the value of ACE-I over ARB as first-line treatment for hypertension management in ADPKD patients.

Usefulness of a Cardiovascular Polypill in the Treatment of Secondary Prevention Patients in Spain: A Cost-effectiveness Study.

INTRODUCTION AND OBJECTIVES: To estimate the health benefits and cost-effectiveness of a polypill intervention (aspirin 100 mg, atorvastatin 20 mg, ramipril 10 mg) compared with multiple monotherapy for secondary prevention of cardiovascular events in adults with a history of myocardial infarction from the perspective of the Spanish National Health System. METHODS: An adapted version of a recently published Markov model developed and validated in Microsoft Excel was used to compare the cost-effectiveness of the polypill with that of its combined monocomponents over a 10-year time horizon. The population included in the model had a mean age of 64.7 years; most were male and had a history of myocardial infarction. The input parameters were obtained from a systematic literature review examining efficacy, adherence, utilities, and costs. The results of the model are expressed in events avoided, incremental costs, incremental life years, incremental quality-adjusted life years, and the incremental cost-effectiveness ratio. RESULTS: Over a 10-year period, use of the cardiovascular polypill instead of its monocomponents simultaneously would avoid 46 nonfatal and 11 fatal cardiovascular events per 1000 patients treated. The polypill would also be a more effective and cheaper strategy. Probabilistic analysis of the base case found a 90.9% probability that the polypill would be a cost-effective strategy compared with multiple monotherapy at a willingness-to-pay of 30 000 euros per quality-adjusted life year. CONCLUSIONS: The polypill would be a cost-effective strategy for the Spanish National Health System with potential clinical benefits.

Cost-Effectiveness of Sacubitril-Valsartan in Patients With Heart Failure With Reduced Ejection Fraction.

BACKGROUND: Sacubitril-valsartan therapy reduces cardiovascular mortality compared with enalapril therapy in patients with heart failure with reduced ejection fraction. OBJECTIVE: To evaluate the cost-effectiveness of sacubitril-valsartan versus angiotensin-converting enzyme inhibitor therapy in patients with chronic heart failure. DESIGN: Markov decision model. DATA SOURCES: Clinical trials, observational analyses, reimbursement data from the Centers for Medicare & Medicaid Services, drug pricing databases, and Centers for Disease Control and Prevention life tables. TARGET POPULATION: Patients at an average age of 64 years, New York Heart Association (NYHA) class II to IV heart failure, and left ventricular ejection fraction of 0.40 or less. TIME HORIZON: Lifetime. PERSPECTIVE: Societal. INTERVENTION: Treatment with sacubitril-valsartan or lisinopril. OUTCOME MEASURES: Life-years, quality-adjusted life-years (QALYs), costs, heart failure hospitalizations, and incremental cost-effectiveness ratios. RESULTS OF BASE-CASE ANALYSIS: The sacubitril-valsartan group experienced 0.08 fewer heart failure hospitalization, 0.69 additional life-year, 0.62 additional QALY, and $29 203 in incremental costs, equating to a cost per QALY gained of $47 053. The cost per QALY gained was $44 531 in patients with NYHA class II heart failure and $58 194 in those with class III or IV heart failure. RESULTS OF SENSITIVITY ANALYSIS: Sacubitril-valsartan treatment was most sensitive to the duration of improved outcomes, with a cost per QALY gained of $120 623 if the duration was limited to the length of the trial (median, 27 months). No variations in other parameters caused the cost to exceed $100 000 per QALY gained. LIMITATION: The benefit of sacubitril-valsartan is based on a single clinical trial. CONCLUSION: Treatment with sacubitril-valsartan provides reasonable value in reducing cardiovascular mortality and morbidity in patients with NYHA class II to IV heart failure. PRIMARY FUNDING SOURCE: U.S. Department of Veterans Affairs and Institute for Clinical and Economic Review.

Modelling of the production of ACE inhibitory hydrolysates of horse mackerel using proteases mixtures.

Fish protein hydrolysates from Mediterranean horse mackerel were produced by using a mixture of two commercial endoproteases (i.e. subtilisin and trypsin) at different levels of substrate concentration (2.5 g L(-1), 5 g L(-1), and 7.5 g L(-1) of protein), temperature (40 °C, 47.5 °C, and 55 °C) and percentage of subtilisin in the enzyme mixture (0%, 25%, 50%, 75% and 100%). A crossed mixture process model was employed to predict the degree of hydrolysis (DH) and the ACE inhibitory activity of the final hydrolysates as a function of the experimental factors. Both models were optimized for a maximum DH and ACE inhibition. A maximum DH (17.1%) was predicted at 2.54 g L(-1) of substrate concentration, 40 °C and an enzyme mixture comprising 38.3% of subtilisin and 61.7% of trypsin. Although its proteolytic activity is limited, the presence of trypsin in the enzyme mixture allowed obtaining higher degrees of hydrolysis at low temperatures, which is desirable to minimize thermal deactivation of the proteins. Similarly, a percentage of ACE inhibition above 48% was attained at 2.5 g L(-1) of protein, 40 °C and a 1 : 1 mixture of both proteases. Higher values of ACE inhibition could be attained by increasing both the temperature and the amount of trypsin in the enzyme mixture (e.g. 50% ACE inhibition at 55 °C and 81.5% of trypsin). Finally, those hydrolysates exhibiting the highest levels of ACE inhibition were subjected to simulated gastrointestinal digestion. These assays confirmed the resistance of active fractions against their degradation by digestive enzymes.