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.

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.

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.

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.

Availability and affordability of cardiovascular disease medicines and their effect on use in high-income, middle-income, and low-income countries: an analysis of the PURE study data.

BACKGROUND: WHO has targeted that medicines to prevent recurrent cardiovascular disease be available in 80% of communities and used by 50% of eligible individuals by 2025. We have previously reported that use of these medicines is very low, but now aim to assess how such low use relates to their lack of availability or poor affordability. METHODS: We analysed information about availability and costs of cardiovascular disease medicines (aspirin, ß blockers, angiotensin-converting enzyme inhibitors, and statins) in pharmacies gathered from 596 communities in 18 countries participating in the Prospective Urban Rural Epidemiology (PURE) study. Medicines were considered available if present at the pharmacy when surveyed, and affordable if their combined cost was less than 20% of household capacity-to-pay. We compared results from high-income, upper middle-income, lower middle-income, and low-income countries. Data from India were presented separately given its large, generic pharmaceutical industry. FINDINGS: Communities were recruited between Jan 1, 2003, and Dec 31, 2013. All four cardiovascular disease medicines were available in 61 (95%) of 64 urban and 27 (90%) of 30 rural communities in high-income countries, 53 (80%) of 66 urban and 43 (73%) of 59 rural communities in upper middle-income countries, 69 (62%) of 111 urban and 42 (37%) of 114 rural communities in lower middle-income countries, eight (25%) of 32 urban and one (3%) of 30 rural communities in low-income countries (excluding India), and 34 (89%) of 38 urban and 42 (81%) of 52 rural communities in India. The four cardiovascular disease medicines were potentially unaffordable for 0·14% of households in high-income countries (14 of 9934 households), 25% of upper middle-income countries (6299 of 24,776), 33% of lower middle-income countries (13,253 of 40,023), 60% of low-income countries (excluding India; 1976 of 3312), and 59% households in India (9939 of 16,874). In low-income and middle-income countries, patients with previous cardiovascular disease were less likely to use all four medicines if fewer than four were available (odds ratio [OR] 0·16, 95% CI 0·04-0·57). In communities in which all four medicines were available, patients were less likely to use medicines if the household potentially could not afford them (0·16, 0·04-0·55). INTERPRETATION: Secondary prevention medicines are unavailable and unaffordable for a large proportion of communities and households in upper middle-income, lower middle-income, and low-income countries, which have very low use of these medicines. Improvements to the availability and affordability of key medicines is likely to enhance their use and help towards achieving WHO's targets of 50% use of key medicines by 2025. FUNDING: Population Health Research Institute, the Canadian Institutes of Health Research, Heart and Stroke Foundation of Ontario, AstraZeneca (Canada), Sanofi-Aventis (France and Canada), Boehringer Ingelheim (Germany and Canada), Servier, GlaxoSmithKline, Novartis, King Pharma, and national or local organisations in participating countries.

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 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.

Improving Adherence to Cardiovascular Therapies: An Economic Evaluation of a Randomized Pragmatic Trial.

OBJECTIVE: Preplanned economic analysis of a pragmatic trial using electronic-medical-record-linked interactive voice recognition (IVR) reminders for enhancing adherence to cardiovascular medications (i.e., statins, angiotensin-converting enzyme inhibitors [ACEIs], and angiotensin receptor blockers [ARBs]). METHODS: Three groups, usual care (UC), IVR, and IVR plus educational materials (IVR+), with 21,752 suboptimally adherent patients underwent follow-up for 9.6 months on average. Costs to implement and deliver the intervention (from a payer perspective) were tracked during the trial. Medical care costs and outcomes were ascertained using electronic medical records. RESULTS: Per-patient intervention costs ranged from $9 to $17 for IVR and from $36 to $47 for IVR+. For ACEI/ARB, the incremental cost-effectiveness ratio for each percent adherence increase was about 3 times higher with IVR+ than with IVR ($6 and $16 for IVR and IVR+, respectively). For statins, the incremental cost-effectiveness ratio for each percent adherence increase was about 7 times higher with IVR+ than with IVR ($6 and $43 for IVR and IVR+, respectively). Considering potential cost offsets from reduced cardiovascular events, the probability of breakeven was the highest for UC, but the IVR-based interventions had a higher probability of breakeven for subgroups with a baseline low-density lipoprotein (LDL) level of more than 100 mg/dl and those with two or more calls. CONCLUSIONS: We found that the use of an automated voice messaging system to promote adherence to ACEIs/ARBs and statins may be cost-effective, depending on a decision maker's willingness to pay for unit increase in adherence. When considering changes in LDL level and downstream medical care offsets, UC is the optimal strategy for the general population. However, IVR-based interventions may be the optimal choice for those with elevated LDL values at baseline.

Cost-effectiveness of medical primary prevention strategies to reduce absolute risk of cardiovascular disease in Tanzania: a Markov modelling study.

BACKGROUND: Cardiovascular disease (CVD) is a growing cause of mortality and morbidity in Tanzania, but contextualized evidence on cost-effective medical strategies to prevent it is scarce. We aim to perform a cost-effectiveness analysis of medical interventions for primary prevention of CVD using the World Health Organization's (WHO) absolute risk approach for four risk levels. METHODS: The cost-effectiveness analysis was performed from a societal perspective using two Markov decision models: CVD risk without diabetes and CVD risk with diabetes. Primary provider and patient costs were estimated using the ingredients approach and step-down methodologies. Epidemiological data and efficacy inputs were derived from systematic reviews and meta-analyses. We used disability- adjusted life years (DALYs) averted as the outcome measure. Sensitivity analyses were conducted to evaluate the robustness of the model results. RESULTS: For CVD low-risk patients without diabetes, medical management is not cost-effective unless willingness to pay (WTP) is higher than US$1327 per DALY averted. For moderate-risk patients, WTP must exceed US$164 per DALY before a combination of angiotensin converting enzyme inhibitor (ACEI) and diuretic (Diu) becomes cost-effective, while for high-risk and very high-risk patients the thresholds are US$349 (ACEI, calcium channel blocker (CCB) and Diu) and US$498 per DALY (ACEI, CCB, Diu and Aspirin (ASA)) respectively. For patients with CVD risk with diabetes, a combination of sulfonylureas (Sulf), ACEI and CCB for low and moderate risk (incremental cost-effectiveness ratio (ICER) US$608 and US$115 per DALY respectively), is the most cost-effective, while adding biguanide (Big) to this combination yielded the most favourable ICERs of US$309 and US$350 per DALY for high and very high risk respectively. For the latter, ASA is also part of the combination. CONCLUSIONS: Medical preventive cardiology is very cost-effective for all risk levels except low CVD risk. Budget impact analyses and distributional concerns should be considered further to assess governments' ability and to whom these benefits will accrue.

Sources of regional variation in Medicare Part D drug spending.

BACKGROUND: Sources of regional variation in spending for prescription drugs under Medicare Part D are poorly understood, and such variation may reflect differences in health status, use of effective treatments, or selection of branded drugs over lower-cost generics. METHODS: We analyzed 2008 Medicare data for 4.7 million beneficiaries for prescription-drug use and expenditures overall and in three drug categories: angiotensin-converting-enzyme (ACE) inhibitors and angiotensin-receptor blockers (ARBs), 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins), and selective serotonin-reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs). Differences in per capita expenditures across hospital-referral regions (HRRs) were decomposed into annual prescription volume and cost per prescription. The ratio of prescriptions filled as branded drugs to all prescriptions filled was calculated. We adjusted all measures for demographic, socioeconomic, and health-status differences. RESULTS: Mean adjusted per capita pharmaceutical spending ranged from $2,413 in the lowest to $3,008 in the highest quintile of HRRs. Most (75.9%) of that difference was attributable to the cost per prescription ($53 vs. $63). Regional differences in cost per prescription explained 87.5% of expenditure variation for ACE inhibitors and ARBs and 56.3% for statins but only 36.1% for SSRIs and SNRIs. The ratio of branded-drug to total prescriptions, which correlated highly with cost per prescription, ranged across HRRs from 0.24 to 0.45 overall and from 0.24 to 0.55 for ACE inhibitors and ARBs, 0.29 to 0.60 for statins, and 0.15 to 0.51 for SSRIs and SNRIs. CONCLUSIONS: Regional variation in Medicare Part D spending results largely from differences in the cost of drugs selected rather than prescription volume. A reduction in branded-drug use in some regions through modification of Part D plan benefits might lower costs without reducing quality of care. (Funded by the National Institute on Aging and others.).

Adherence to Metformin, Statins, and ACE/ARBs Within the Diabetes Health Plan (DHP).

BACKGROUND: Reducing patient cost-sharing and engaging patients in disease management activities have been shown to increase uptake of evidence-based care. OBJECTIVE: To evaluate the effect of employer purchase of a disease-specific plan with reduced cost-sharing and disease management (the Diabetes Health Plan/DHP) on medication adherence among eligible employees and dependents. DESIGN: Employer-level "intent to treat" cohort study, including data from eligible employees and their dependents with diabetes, regardless of whether they were enrolled in the DHP. SETTING: Employers that contracted with a large national health plan administrator in 2009, 2010, and/or 2011. PARTICIPANTS: Ten employers that purchased the DHP and 191 employers that did not (controls). Inverse probability weighting (IPW) estimation was used to adjust for inter-group differences. INTERVENTION: The DHP includes free or low-cost medications and physician visits. Enrollment strategies and specific benefit designs are determined by the employer and vary in practice. DHP participants are notified up front that they must engage in their own health care (e.g., receiving diabetes-related screening) in order to remain enrolled. MAIN OUTCOME MEASURE: Mean employee adherence to metformin, statins, and ACE/ARBs at the employer level at one year post-DHP implementation, as measured by the proportion of days covered (PDC). RESULTS: Baseline adherence to the three medications was similar across DHP and control employers, ranging from 64 to 69 %. In the first year after DHP implementation, predicted employer-level adherence for metformin (+4.9 percentage points, p = 0.017), statins (+4.8, p = 0.019), and ACE/ARBs (+4.4, p = 0.02) was higher with DHP purchase. LIMITATIONS: Non-randomized, observational study. CONCLUSIONS: The Diabetes Health Plan, an innovative health plan that combines reduced cost-sharing and disease management with an up-front requirement of enrollee participation in his or her own health care, is associated with a modest improvement in medication adherence at 12 months.

Income differences in the type of antihypertensive medicines used in ambulatory settings in Finland: a register-based study.

PURPOSE: The objective of this study was to explore income differences in the prevalence of moderate-to-severe hypertension, and among patients, in the use and costs of medicines. METHODS: Personal income was used to classify ≥25-year-old population in quintiles (QI-QV). Patients (N = 497,560) with moderate-to-severe hypertension were identified using special refund entitlements. Medicine use and costs derived from prescription register. Direct standardisation and multivariate regression were used to adjust for demographics and comorbidities. RESULTS: Low income was associated with higher prevalence of moderate-to-severe hypertension (overall 13%). After adjusting for age, gender, residence, diabetes and coronary heart disease, nearly all patients purchased at least one antihypertensive medicine (93 vs. 96% in QI and QV). Differences in the purchased quantities were small (mean estimates 1028 vs. 1054 defined daily doses (DDDs)/patient/year in QIV and QI). High-income patients were more likely to use angiotensin receptor blockers (37 vs. 54% in QI and QV). Low-income patients were more likely to use beta-blockers (59 vs. 49%, respectively) and ACE inhibitors (35 vs. 28%, respectively). Higher income was associated with higher annual out-of-pocket costs (mean €66 vs. €71 in QI and QV) and reimbursements (€144 vs. €163, respectively). CONCLUSIONS: Use of more expensive medicines contributed to higher costs among patients with higher incomes.

Routine echocardiography screening for asymptomatic left ventricular dysfunction in childhood cancer survivors: a model-based estimation of the clinical and economic effects.

BACKGROUND: Childhood cancer survivors treated with cardiotoxic therapies are recommended to have routine cardiac assessment every 1 to 5 years, but the long-term benefits are uncertain. OBJECTIVE: To estimate the cost-effectiveness of routine cardiac assessment to detect asymptomatic left ventricular dysfunction and of angiotensin-converting enzyme inhibitor and ß-blocker treatment to reduce congestive heart failure (CHF) incidence in childhood cancer survivors. DESIGN: Simulation model. DATA SOURCES: Literature, including data from the Childhood Cancer Survivor Study. TARGET POPULATION: Childhood cancer survivors. TIME HORIZON: Lifetime. PERSPECTIVE: Societal. INTERVENTION: Interval-based echocardiography assessment every 1, 2, 5, or 10 years, with subsequent angiotensin-converting enzyme inhibitor or ß-blocker treatment for patients with positive test results. OUTCOME MEASURES: Lifetime risk for systolic CHF, lifetime costs, quality-adjusted life expectancy, and incremental cost-effectiveness ratios (ICERs). RESULTS OF BASE-CASE ANALYSIS: The lifetime risk for systolic CHF among 5-year childhood cancer survivors aged 15 years was 18.8% without routine cardiac assessment (average age at onset, 58.8 years). Routine echocardiography reduced lifetime risk for CHF by 2.3% (with assessment every 10 years) to 8.7% (annual assessment). The ICER for assessment every 10 years was $111 600 per quality-adjusted life-year (QALY) compared with no assessment. Assessment every 5 years had an ICER of $117 900 per QALY, and ICERs for more frequent assessment exceeded $165 000 per QALY. RESULTS OF SENSITIVITY ANALYSIS: Results were sensitive to treatment effectiveness, absolute excess risk for CHF, and asymptomatic left ventricular dysfunction asymptomatic period. The probability that assessment every 10 or 5 years was preferred at a $100 000-per-QALY threshold was 0.33 for the overall cohort. LIMITATION: Treatment effectiveness was based on adult data. CONCLUSION: Current recommendations for cardiac assessment may reduce CHF incidence, but less frequent assessment may be preferable.

Cost-effectiveness of the children's oncology group long-term follow-up screening guidelines for childhood cancer survivors at risk for treatment-related heart failure.

BACKGROUND: Childhood cancer survivors treated with anthracyclines are at high risk for asymptomatic left ventricular dysfunction (ALVD), subsequent heart failure, and death. The consensus-based Children's Oncology Group (COG) Long-Term Follow-up Guidelines recommend lifetime echocardiographic screening for ALVD. OBJECTIVE: To evaluate the efficacy and cost-effectiveness of the COG guidelines and to identify more cost-effective screening strategies. DESIGN: Simulation of life histories using Markov health states. DATA SOURCES: Childhood Cancer Survivor Study; published literature. TARGET POPULATION: Childhood cancer survivors. TIME HORIZON: Lifetime. PERSPECTIVE: Societal. INTERVENTION: Echocardiographic screening followed by angiotensin-converting enzyme (ACE) inhibitor and ß-blocker therapies after ALVD diagnosis. OUTCOME MEASURES: Quality-adjusted life-years (QALYs), costs, incremental cost-effectiveness ratios (ICERs) in dollars per QALY, and cumulative incidence of heart failure. RESULTS OF BASE-CASE ANALYSIS: The COG guidelines versus no screening have an ICER of $61 500, extend life expectancy by 6 months and QALYs by 1.6 months, and reduce the cumulative incidence of heart failure by 18% at 30 years after cancer diagnosis. However, less frequent screenings are more cost-effective than the guidelines and maintain 80% of the health benefits. RESULTS OF SENSITIVITY ANALYSIS: The ICER was most sensitive to the magnitude of ALVD treatment efficacy; higher treatment efficacy resulted in lower ICER. LIMITATION: Lifetime non-heart failure mortality and the cumulative incidence of heart failure more than 20 years after diagnosis were extrapolated; the efficacy of ACE inhibitor and ß-blocker therapy in childhood cancer survivors with ALVD is undetermined (or unknown). CONCLUSION: The COG guidelines could reduce the risk for heart failure in survivors at less than $100 000/QALY. Less frequent screening achieves most of the benefits and would be more cost-effective than the COG guidelines.

Full coverage for preventive medications after myocardial infarction.

BACKGROUND: Adherence to medications that are prescribed after myocardial infarction is poor. Eliminating out-of-pocket costs may increase adherence and improve outcomes. METHODS: We enrolled patients discharged after myocardial infarction and randomly assigned their insurance-plan sponsors to full prescription coverage (1494 plan sponsors with 2845 patients) or usual prescription coverage (1486 plan sponsors with 3010 patients) for all statins, beta-blockers, angiotensin-converting-enzyme inhibitors, or angiotensin-receptor blockers. The primary outcome was the first major vascular event or revascularization. Secondary outcomes were rates of medication adherence, total major vascular events or revascularization, the first major vascular event, and health expenditures. RESULTS: Rates of adherence ranged from 35.9 to 49.0% in the usual-coverage group and were 4 to 6 percentage points higher in the full-coverage group (P<0.001 for all comparisons). There was no significant between-group difference in the primary outcome (17.6 per 100 person-years in the full-coverage group vs. 18.8 in the usual-coverage group; hazard ratio, 0.93; 95% confidence interval [CI], 0.82 to 1.04; P=0.21). The rates of total major vascular events or revascularization were significantly reduced in the full-coverage group (21.5 vs. 23.3; hazard ratio, 0.89; 95% CI, 0.90 to 0.99; P=0.03), as was the rate of the first major vascular event (11.0 vs. 12.8; hazard ratio, 0.86; 95% CI, 0.74 to 0.99; P=0.03). The elimination of copayments did not increase total spending ($66,008 for the full-coverage group and $71,778 for the usual-coverage group; relative spending, 0.89; 95% CI, 0.50 to 1.56; P=0.68). Patient costs were reduced for drugs and other services (relative spending, 0.74; 95% CI, 0.68 to 0.80; P<0.001). CONCLUSIONS: The elimination of copayments for drugs prescribed after myocardial infarction did not significantly reduce rates of the trial's primary outcome. Enhanced prescription coverage improved medication adherence and rates of first major vascular events and decreased patient spending without increasing overall health costs. (Funded by Aetna and the Commonwealth Fund; MI FREEE ClinicalTrials.gov number, NCT00566774.).

Therapeutic substitution post-patent expiry: the cases of ACE inhibitors and proton pump inhibitors.

This paper examines whether there is a switch in total (originator and generic) consumption after generic entry from molecules that face generic competition towards other molecules of the same class, which are still in-patent. Data from six European countries for the time period 1991 to 2006 are used to study the cases of angiotensin-converting enzyme inhibitors and proton pump inhibitors. Empirical evidence shows that patent expiry of captopril and enalapril led to a switch in total (off-patent originator and generic) consumption towards other in-patent angiotensin-converting enzyme inhibitors, whereas patent expiry of omeprazole led to a switch in consumption towards other proton pump inhibitors. This phenomenon makes generic policies ineffective and results in an increase in pharmaceutical expenditure due to the absence of generic alternatives in the market of in-patent molecules.

Economic evaluations of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers in type 2 diabetic nephropathy: a systematic review.

BACKGROUND: Structured comparison of pharmacoeconomic analyses for ACEIs and ARBs in patients with type 2 diabetic nephropathy is still lacking. This review aims to systematically review the cost-effectiveness of both ACEIs and ARBs in type 2 diabetic patients with nephropathy. METHODS: A systematic literature search was performed in MEDLINE and EMBASE for the period from November 1, 1999 to Oct 31, 2011. Two reviewers independently assessed the quality of the articles included and extracted data. All cost-effectiveness results were converted to 2011 Euros. RESULTS: Up to October 2011, 434 articles were identified. After full-text checking and quality assessment, 30 articles were finally included in this review involving 39 study settings. All 6 ACEIs studies were literature-based evaluations which synthesized data from different sources. Other 33 studies were directed at ARBs and were designed based on specific trials. The Markov model was the most common decision analytic method used in the evaluations. From the cost-effectiveness results, 37 out of 39 studies indicated either ACEIs or ARBs were cost-saving comparing with placebo/conventional treatment, such as amlodipine. A lack of evidence was assessed for valid direct comparison of cost-effectiveness between ACEIs and ARBs. CONCLUSION: There is a lack of direct comparisons of ACEIs and ARBs in existing economic evaluations. Considering the current evidence, both ACEIs and ARBs are likely cost-saving comparing with conventional therapy, excluding such RAAS inhibitors.

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.

Community care in England: reducing socioeconomic inequalities in heart failure.

BACKGROUND: Socioeconomic deprivation is associated with increased heart failure (HF) incidence, hospitalization rates, and mortality. However, whether the delivery of survival-enhancing medical therapy is equitable remains uncertain. We examined secular trends in the uptake of key medical therapies (angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, ß-blockers, spironolactone) stratified by socioeconomic circumstances in patients with HF. Secondary analyses examined trends in HF incidence, prevalence, and survival. METHODS AND RESULTS: This study was a cross-sectional observational analysis of nationally representative primary care data from England. Treatments for patients with HF in 1999 and 2007 (n=13 330) were extracted from the General Practice Research Database. Socioeconomic circumstances were defined with the Index of Multiple Deprivation 2007, a weighted composite of 7 area-level deprivation domains. Treatment uptake estimates were age standardized. The incidence and prevalence of HF decreased year to year. Although clear socioeconomic gradients in both the incidence and prevalence of HF were apparent, the absolute difference between most and least deprived reduced over time. Uptake of therapies improved over time in both men and women. Angiotensin-converting enzyme inhibitor/angiotensin receptor blocker uptake increased from 46% to 64%, ß-blocker uptake from 12% to 41%, and spironolactone uptake from 3% to 20%. Modest age and sex inequalities were apparent. However, no consistent socioeconomic gradients were observed in either treatment or case fatality. CONCLUSIONS: Socioeconomic gradients in the incidence and prevalence of HF are reducing. Treatment is generally equitable and independent of socioeconomic circumstances. Most important, no significant inequality in outcomes was apparent. Future strategies should continue to address inequalities in the underlying causes of HF and to increase overall treatment levels further.

To treat or not to treat? Cost-effectiveness of ace inhibitors in non-diabetic advanced renal disease - a Dutch perspective.

BACKGROUND: Treating non-diabetic proteinuric patients with advanced renal disease with an angiotensin-converting enzyme (ACE) inhibitor is still subject to discussion. This study aims to determine the cost-effectiveness of ACE inhibitor therapy in this patient population in the Netherlands. METHODS: We compared two strategies: first, treating patients with advanced renal disease with an ACE inhibitor and no-treatment. A lifetime Markov decision model was developed simulating the progression of renal disease and using published data on costs and health outcomes. A health care perspective was adopted. RESULTS: In the base-case analysis, treatment with ACE inhibitors leads to higher benefits and lower costs and dominates the no-treatment strategy. Sensitivity analysis shows that the probability of savings is 83%. CONCLUSION: ACE inhibitor treatment for non-diabetic patients with advanced renal disease in the Netherlands is highly cost-effective and should therefore be considered.