Sacubitril-valsartan versus enalapril for acute decompensated heart failure: a cost-effectiveness analysis.

BACKGROUND: The Comparison of Sacubitril-Valsartan versus Enalapril on Effect on NT-proBNP in Patients Stabilised from an Acute Heart Failure Episode (PIONEER-HF) trial demonstrated significant reductions in N-terminal pro-B-type natriuretic peptide. Our study explored the cost-effectiveness of the use of sacubitril-valsartan versus enalapril in acute decompensated heart failure from the Australian healthcare perspective. METHODS: A Markov model was designed using data from the PIONEER-HF trial to model the clinical progress and costs of patients over a lifetime time horizon. The model consisted of three health states: 'alive and event-free', 'alive after non-fatal hospitalisation for acute decompensated heart failure' or 'dead'. Costs and utilities were estimated from published sources. The cost of sacubitril-valsartan (per the Australian pharmaceutical benefits schedule) was AU$7.08/day. Outcomes of interest were the incremental cost-effectiveness ratios in terms of cost per quality-adjusted life year gained and cost per year of life saved. Cost and benefits were discounted at 5.0% per annum. RESULTS: Compared to enalapril, sacubitril-valsartan was estimated to cost an additional AU$7464 (discounted) per person, but lead to 0.127 years of life saved (discounted) and 0.096 quality-adjusted life years gained (discounted) over a lifetime analysis. These equated to incremental cost-effectiveness ratios of AU$58,629/year of life saved (US$41,795, EU€58,629, GBP£32,001) and AU$77,889/quality-adjusted life year gained (US$55,526, EU€49,202, GBP£42,504). We have assumed a threshold of AU$50,000/quality-adjusted life year gained to suggest cost-effectiveness. CONCLUSIONS: At its current acquisition price, sacubitril-valsartan in comparison to enalapril is not likely to be cost-effective in the management of acute decompensated heart failure in Australia. A price reduction of more than 25% would confer cost-effectiveness.

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.

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.

PARADIGM-HF Trial: Secondary Analyses Address Unanswered Questions.

Our aim was to summarize published secondary analyses of the PARADIGM-HF trial. In the original trial, published in September 2014, sacubitril/valsartan significantly reduced the primary composite outcome of cardiovascular death or heart failure hospitalization compared to enalapril. This summary provides a resource for clinicians to review subsequent analyses of the landmark trial evaluating the benefit of sacubitril/valsartan in various subgroups and providing information regarding optimal use of this new therapy in the broader heart failure population. A full list of publications of the existing PARDADIGM-HF post hoc analyses was obtained and summarized, grouped by focus (e.g., severity of illness, tolerability). Twenty-six publications and one abstract analyzing the PARADIGM-HF trial were reviewed, summarizing the most important results that compared the benefits of sacubitril/valsartan to enalapril, including pertinent subgroup information from each analysis. Key publications evaluated the treatment effect of sacubitril/valsartan based on heart failure severity (i.e., ejection fraction or heart failure risk scores), impact on alternate outcomes, influence of additional therapies, tolerability in patients with comorbidities (i.e., diabetes), long-term benefits, and cost-effectiveness. In addition, nine ongoing phase III and phase IV clinical trials with sacubitril/valsartan were briefly summarized to address potential future uses in more extensive heart failure settings. The benefit of sacubitril/valsartan over enalapril for the primary endpoint in the PARADIGM-HF trial is maintained throughout numerous secondary analyses. Though the subgroups analyzed are based on participants from a single clinical trial, clinicians can more confidently incorporate this novel therapy into practice with expanded knowledge of these existing analyses as well as ongoing prospective trials.

Cost-effectiveness of sacubitril/valsartan versus enalapril in patients with heart failure and reduced ejection fraction.

BACKGROUND: Sacubitril/valsartan reduces cardiovascular death and hospitalizations for heart failure (HF). However, decision-makers need to determine whether its benefits are worth the additional costs, given the low-cost generic status of traditional standard of care. AIMS: To evaluate the cost-effectiveness of sacubitril/valsartan compared to enalapril in patients with HF and reduced ejection fraction, from the Singapore healthcare payer perspective. METHODS: A Markov model was developed to project clinical and economic outcomes of sacubitril/valsartan vs enalapril for 66-year-old patients with HF over 10 years. Key health states included New York Heart Association classes I-IV and deaths; patients in each state incurred a monthly risk of hospitalization for HF and cardiovascular death. Sacubitril/valsartan benefits were modeled by applying the hazard ratios (HRs) in PARADIGM-HF trial to baseline probabilities. Primary model outcomes were total and incremental costs and quality-adjusted life years (QALYs) and the incremental cost-effectiveness ratio (ICER) for sacubitril/valsartan relative to enalapril Results: Compared to enalapril, sacubitril/valsartan was associated with an ICER of SGD 74,592 (USD 55,198) per QALY gained. A major driver of cost-effectiveness was the cardiovascular mortality benefit of sacubitril/valsartan. The uncertainty of this treatment benefit in the Asian sub-group was tested in sensitivity analyses using a HR of 1 as an upper limit, where the ICERs ranged from SGD 41,019 (USD 30,354) to SGD 1,447,103 (USD 1,070,856) per QALY gained. Probabilistic sensitivity analyses showed the probability of sacubitril/valsartan being cost-effective was below 1%, 12%, and 71% at SGD 20,000, SGD 50,000, and SGD 100,000 per QALY gained, respectively. CONCLUSIONS: At the current daily price sacubitril/valsartan may not represent good value for limited healthcare dollars compared to enalapril in reducing cardiovascular morbidity and mortality in HF in the Singapore healthcare setting. This study highlights the cost-benefit trade-off that healthcare professionals and patients face when considering therapy.

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 chronic heart-failure patients with reduced ejection fraction.

AIMS: We aimed to assess the cost effectiveness of sacubitril/valsartan compared to angiotensin-converting enzyme inhibitors (ACEIs) for the treatment of individuals with chronic heart failure and reduced-ejection fraction (HFrEF) from the perspective of the Swiss health care system. METHODS: The cost-effectiveness analysis was implemented as a lifelong regression-based cohort model. We compared sacubitril/valsartan with enalapril in chronic heart failure patients with HFrEF and New York-Heart Association Functional Classification II-IV symptoms. Regression models based on the randomised clinical phase III PARADIGM-HF trials were used to predict events (all-cause mortality, hospitalisations, adverse events and quality of life) for each treatment strategy modelled over the lifetime horizon, with adjustments for patient characteristics. Unit costs were obtained from Swiss public sources for the year 2014, and costs and effects were discounted by 3%. The main outcome of interest was the incremental cost-effectiveness ratio (ICER), expressed as cost per quality-adjusted life years (QALYs) gained. Deterministic sensitivity analysis (DSA) and scenario and probabilistic sensitivity analysis (PSA) were performed. RESULTS: In the base-case analysis, the sacubitril/valsartan strategy showed a decrease in the number of hospitalisations (6.0% per year absolute reduction) and lifetime hospital costs by 8.0% (discounted) when compared with enalapril. Sacubitril/valsartan was predicted to improve overall and quality-adjusted survival by 0.50 years and 0.42 QALYs, respectively. Additional net-total costs were CHF 10 926. This led to an ICER of CHF 25 684. In PSA, the probability of sacubitril/valsartan being cost-effective at thresholds of CHF 50 000 was 99.0%. CONCLUSION: The treatment of HFrEF patients with sacubitril/valsartan versus enalapril is cost effective, if a willingness-to-pay threshold of CHF 50 000 per QALY gained ratio is assumed.

Cost-effectiveness Analysis of Sacubitril/Valsartan vs Enalapril in Patients With Heart Failure and Reduced Ejection Fraction.

IMPORTANCE: The angiotensin receptor neprilysin inhibitor sacubitril/valsartan was associated with a reduction in cardiovascular mortality, all-cause mortality, and hospitalizations compared with enalapril. Sacubitril/valsartan has been approved for use in heart failure (HF) with reduced ejection fraction in the United States and cost has been suggested as 1 factor that will influence the use of this agent. OBJECTIVE: To estimate the cost-effectiveness of sacubitril/valsartan vs enalapril in the United States. DESIGN, SETTING, AND PARTICIPANTS: Data from US adults (mean [SD] age, 63.8 [11.5] years) with HF with reduced ejection fraction and characteristics similar to those in the PARADIGM-HF trial were used as inputs for a 2-state Markov model simulated HF. Risks of all-cause mortality and hospitalization from HF or other reasons were estimated with a 30-year time horizon. Quality of life was based on trial EQ-5D scores. Hospital costs combined Medicare and private insurance reimbursement rates; medication costs included the wholesale acquisition cost for sacubitril/valsartan and enalapril. A discount rate of 3% was used. Sensitivity analyses were performed on key inputs including: hospital costs, mortality benefit, hazard ratio for hospitalization reduction, drug costs, and quality-of-life estimates. MAIN OUTCOMES AND MEASURES: Hospitalizations, quality-adjusted life-years (QALYs), costs, and incremental costs per QALY gained. RESULTS: The 2-state Markov model of US adult patients (mean age, 63.8 years) calculated that there would be 220 fewer hospital admissions per 1000 patients with HF treated with sacubitril/valsartan vs enalapril over 30 years. The incremental costs and QALYs gained with sacubitril/valsartan treatment were estimated at $35 512 and 0.78, respectively, compared with enalapril, equating to an incremental cost-effectiveness ratio (ICER) of $45 017 per QALY for the base-case. Sensitivity analyses demonstrated ICERs ranging from $35 357 to $75 301 per QALY. CONCLUSIONS AND RELEVANCE: For eligible patients with HF with reduced ejection fraction, the Markov model calculated that sacubitril/valsartan would increase life expectancy at an ICER consistent with other high-value accepted cardiovascular interventions. Sensitivity analyses demonstrated sacubitril/valsartan would remain cost-effective vs enalapril.

Cost-Effectiveness of Sacubitril-Valsartan Combination Therapy Compared With Enalapril for the Treatment of Heart Failure With Reduced Ejection Fraction.

OBJECTIVES: The objective of this study was to determine the cost-effectiveness and cost per quality-adjusted life year (QALY) gained of sacubitril-valsartan relative to enalapril for treatment of heart failure with reduced ejection fraction (HFrEF). BACKGROUND: Compared with enalapril, combination angiotensin receptor-neprilysin inhibition (ARNI), as is found in sacubitril-valsartan, reduces cardiovascular death and heart failure hospitalization rates in patients with HFrEF. METHODS: Using a Markov model, costs, effects, and cost-effectiveness were estimated for sacubitril-valsartan and enalapril therapies for the treatment of HFrEF. Patients were 60 years of age at model entry and were modeled over a lifetime (40 years) from a third-party payer perspective. Clinical probabilities were derived predominantly from PARADIGM-HF (Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure). All costs and effects were discounted at a 3% rate annually and are presented in 2015 U.S. dollars. RESULTS: In the base case, sacubitril-valsartan, compared with enalapril, was more costly ($60,391 vs. $21,758) and more effective (6.49 vs. 5.74 QALYs) over a lifetime. The cost-effectiveness of sacubitril-valsartan was highly dependent on duration of treatment, ranging from $249,411 per QALY at 3 years to $50,959 per QALY gained over a lifetime. CONCLUSIONS: Sacubitril-valsartan may be a cost-effective treatment option depending on the willingness-to-pay threshold. Future investigations should incorporate real-world evidence with sacubitril-valsartan to further inform decision making.

An economic evaluation of antihypertensive therapies based on clinical trials.

OBJECTIVE: Hypertension is a major issue in public health, and the financial costs associated with hypertension continue to increase. Cost-effectiveness studies focusing on antihypertensive drug combinations, however, have been scarce. The cost-effectiveness ratios of the traditional treatment (hydrochlorothiazide and atenolol) and the current treatment (losartan and amlodipine) were evaluated in patients with grade 1 or 2 hypertension (HT1-2). For patients with grade 3 hypertension (HT3), a third drug was added to the treatment combinations: enalapril was added to the traditional treatment, and hydrochlorothiazide was added to the current treatment. METHODS: Hypertension treatment costs were estimated on the basis of the purchase prices of the antihypertensive medications, and effectiveness was measured as the reduction in systolic blood pressure and diastolic blood pressure (in mm Hg) at the end of a 12-month study period. RESULTS: When the purchase price of the brand-name medication was used to calculate the cost, the traditional treatment presented a lower cost-effectiveness ratio [US$/mm Hg] than the current treatment in the HT1-2 group. In the HT3 group, however, there was no difference in cost-effectiveness ratio between the traditional treatment and the current treatment. The cost-effectiveness ratio differences between the treatment regimens maintained the same pattern when the purchase price of the lower-cost medication was used. CONCLUSIONS: We conclude that the traditional treatment is more cost-effective (US$/mm Hg) than the current treatment in the HT1-2 group. There was no difference in cost-effectiveness between the traditional treatment and the current treatment for the HT3 group.

An economic evaluation of antihypertensive therapies based on clinical trials

OBJECTIVE: Hypertension is a major issue in public health, and the financial costs associated with hypertension continue to increase. Cost-effectiveness studies focusing on antihypertensive drug combinations, however, have been scarce. The cost-effectiveness ratios of the traditional treatment (hydrochlorothiazide and atenolol) and the current treatment (losartan and amlodipine) were evaluated in patients with grade 1 or 2 hypertension (HT1-2). For patients with grade 3 hypertension (HT3), a third drug was added to the treatment combinations: enalapril was added to the traditional treatment, and hydrochlorothiazide was added to the current treatment. METHODS: Hypertension treatment costs were estimated on the basis of the purchase prices of the antihypertensive medications, and effectiveness was measured as the reduction in systolic blood pressure and diastolic blood pressure (in mm Hg) at the end of a 12-month study period. RESULTS: When the purchase price of the brand-name medication was used to calculate the cost, the traditional treatment presented a lower cost-effectiveness ratio [US$/mm Hg] than the current treatment in the HT1-2 group. In the HT3 group, however, there was no difference in cost-effectiveness ratio between the traditional treatment and the current treatment. The cost-effectiveness ratio differences between the treatment regimens maintained the same pattern when the purchase price of the lower-cost medication was used. CONCLUSIONS: We conclude that the traditional treatment is more cost-effective (US$/mm Hg) than the current treatment in the HT1-2 group. There was no difference in cost-effectiveness between the traditional treatment and the current treatment for the HT3 group.

Cost-utility analysis of eprosartan compared to enalapril in primary prevention and nitrendipine in secondary prevention in Europe--the HEALTH model.

OBJECTIVE: To investigate the cost-utility of eprosartan versus enalapril (primary prevention) and versus nitrendipine (secondary prevention) on the basis of head-to-head evidence from randomized controlled trials. METHODS: The HEALTH model (Health Economic Assessment of Life with Teveten for Hypertension) is an object-oriented probabilistic Monte Carlo simulation model. It combines a Framingham-based risk calculation with a systolic blood pressure approach to estimate the relative risk reduction of cardiovascular and cerebrovascular events based on recent meta-analyses. In secondary prevention, an additional risk reduction is modeled for eprosartan according to the results of the MOSES study ("Morbidity and Mortality after Stroke--Eprosartan Compared to Nitrendipine for Secondary Prevention"). Costs and utilities were derived from published estimates considering European country-specific health-care payer perspectives. RESULTS: Comparing eprosartan to enalapril in a primary prevention setting the mean costs per quality adjusted life year (QALY) gained were highest in Germany (Euro 24,036) followed by Belgium (Euro 17,863), the UK (Euro 16,364), Norway (Euro 13,834), Sweden (Euro 11,691) and Spain (Euro 7918). In a secondary prevention setting (eprosartan vs. nitrendipine) the highest costs per QALY gained have been observed in Germany (Euro 9136) followed by the UK (Euro 6008), Norway (Euro 1695), Sweden (Euro 907), Spain (Euro -2054) and Belgium (Euro -5767). CONCLUSIONS: Considering a Euro 30,000 willingness-to-pay threshold per QALY gained, eprosartan is cost-effective as compared to enalapril in primary prevention (patients >or=50 years old and a systolic blood pressure >or=160 mm Hg) and cost-effective as compared to nitrendipine in secondary prevention (all investigated patients).

Cost analysis of amlodipine versus enalapril in patients with coronary artery disease and normal blood pressure: findings from the CAMELOT economic substudy.

OBJECTIVES: To analyse 2-year hospitalization and cost data collected during a prospective, double-blind, randomized, controlled trial comparing amlodipine, enalapril and placebo in normotensive patients with coronary artery disease (CAD). METHODS: All patients who were enrolled in the CAMELOT study were included in this economic substudy. Patients with CAD and normal blood pressure were randomized to amlodipine, enalapril or placebo, and followed up for 24 months (between 1999 and 2004). Data on hospitalizations and medication use were obtained from the clinical trial. Costs were assigned from secondary sources. Total costs ($US, year 2004 values) were estimated as the sum of costs associated with cardiovascular hospitalizations, study medications and concomitant cardiovascular medications. Costs and resource use were analysed by treatment arm overall and for selected patient subgroups. Cost differences were evaluated using nonparametric bootstrap techniques. RESULTS: Of 1991 patients enrolled, 663 were treated with amlodipine, 673 were treated with enalapril and 655 were treated with placebo. Significantly fewer patients were hospitalized for cardiovascular reasons in the amlodipine group (16.4%) than in the placebo group (22.7%; p < 0.01), but not compared with the enalapril group (20.1%; p = 0.09). The amlodipine group also had numerically fewer days in hospital per patient (1.1) than the enalapril (1.3) and placebo (1.5) groups. Mean 2-year per-patient costs in the amlodipine group were estimated to be $US 609 and $US 717 lower than for the placebo and enalapril groups, respectively. CONCLUSIONS: These results suggest that use of amlodipine may reduce costs of care among CAD patients with normal blood pressure.

The impact of generic substitution on price competition in Finland.

Generic substitution by pharmacists was introduced in April 2003 in Finnish pharmaceutical markets. This article examines the impact of generic substitution on price development. This study examined all of the 2,100 substitutable drugs in Finland. The impact of generic substitution on price competition was significant. The average price of substitutable drugs decreased by more than 10%. However, the price development was uneven; some prices increased whereas others decreased by more than 50%. The most important factors that influenced the price development were the number of competitors, whether the drug was originator or generic and the width of the price band.

Comparison of health costs associated with treatment of hypertension with a calcium channel blocker and angiotensin-converting enzyme inhibitor in the United States and Japan.

Hypertension is prevalent in over 25% of populations in developed countries, and poses an increasing economic burden on health resources. Therefore it is predicted that future medical treatment of hypertension will be increasingly affected by cost considerations. Several classes of antihypertensive drugs are used as first-line agents for the treatment of hypertension, but the economic impact of using these agents in different countries remains to be addressed. In this study, we compared health costs associated with treatment of hypertension using the calcium channel blocker amlodipine and the angiotensin-converting enzyme inhibitor enalapril in the US and Japan. Pharmaceutical costs and hospitalization costs were analyzed from established databases. The data for the prevalence of myocardial infarction and stroke were derived from the Framingham study and the Hisayama study. Analysis of the economic impacts using relative risk differences between the calcium channel blocker and angiotensin-converting enzyme inhibitor together with regional hospitalization costs resulted in an apparent 11.2 billion yen health cost reduction in favor of the calcium channel blocker in the case of Japan, in contrast to an apparent 5.7 billion yen reduction in favor of the angiotensin-converting enzyme inhibitor in the case of the US. The trends in Japan for 2000 and 2004 were similar. These results suggest that there are regional differences in the health costs associated with different classes of hypertensive agents, which could affect national policies on the choice of antihypertensive drugs. It is predicted that future treatment of hypertension will be increasingly tailored to the epidemiologic profiles and medical costs of individual communities.

[Comparative efficacy of fixed dose combinations of enalapril with hydrochlorothiazide and captopril with hydrochlorothiazide in patients with high risk hypertension].

Clinical effectiveness and tolerability of o.d. use of fixed dose combinations of enalapril (10 mg) with hydrochlorothiazide (25 mg) (Enap H) and captopril (50 mg) with hydrochlorothiazide (25 mg) (Capozide) were compared in a randomized study on 60 patients with I-II degree high and very high risk hypertension. Study duration was 6 months, number of patients in each of parallel groups -- 30. Antihypertensive activity, ability to improve arterial elasticity and T/P parameter, cost/efficacy index of enalapril (10 mg) plus hydrochlorothiazide (25 mg) combination was found to be superior to those of captopril (50 mg) plus hydrochlorothiazide (25 mg) combination.

Drug costs developments after patent expiry of enalapril, fluoxetine and ranitidine: a study conducted for the Netherlands.

BACKGROUND: In order to increase price competition, government regulations focus on controlling drug costs. Drug costs after patent expiry are an area of particular interest because the substitution of branded medication with generics represents an opportunity for lowering drug costs. However, drug costs may not decrease after patent expiry, because of a lack of price competition and different national pricing systems. AIM: The aim of this study was to investigate the trends in the use of generics after patent expiry for enalapril, fluoxetine and ranitidine and the subsequent changes, if any, in the costs of these medications. METHODS: A drug-utilisation study was performed using data from a large sample of Dutch pharmacies. Both volumes (measured as defined daily doses [DDD] per 1000 population) as well as drug costs (calculated per DDD) prior to and after patent expiry were calculated. Costs per DDD were compared using trend-line analysis. In addition, the relative market shares of the different trade channels (branded, parallel imported and generic) were compared before and after patent expiry. RESULTS: The costs per DDD decreased for all three drugs and, as expected, these costs decrease more rapidly after patent expiry. Significant differences in the trend lines were found for enalapril and fluoxetine. CONCLUSIONS: Despite relatively high reimbursement prices for generics in the Netherlands, this example from the Dutch pharmaceutical market demonstrates the benefit of generic substitution for containing pharmaceutical costs, which contrasts with concerns raised by the Dutch government.