Cost-Effectiveness Analysis of Ezetimibe as the Add-on Treatment to Moderate-Dose Rosuvastatin versus High-Dose Rosuvastatin in the Secondary Prevention of Cardiovascular Diseases in China: A Markov Model Analysis.

BACKGROUND: For patients with inadequate control of cholesterol using moderate-dose statins in the secondary prevention of cardiovascular diseases (CVD), either doubling the dose of statins or adding ezetimibe should be considered. The cost-effectiveness of them is unknown in the Chinese context. The aim of this study is to compare the cost and effectiveness of the two regimens, and estimate the incremental cost-effectiveness ratio (ICER). METHODS: A Markov model of five health statuses were used to estimate long-term costs and quality-adjusted life-years (QALYs) of the two treatment regimens from the healthcare perspective. The effectiveness data used to calculate the transition probability was based on a previously published randomized trial. The utility data was gathered from literature and the costs were gathered from the electronic medical record system of West China Hospital in Chinese Yuan (CNY) in 2017 price. One-way sensitivity analysis and probabilistic sensitivity analysis were conducted. RESULTS: The ICER for ezetimibe plus moderate-dose rosuvastatin was 47,102.99 CNY per QALY for 20 years simulation, which did not reach the threshold of per capita gross domestic product (GDP) of 59,660 CNY per QALY in 2017 in China. Non-CVD-related mortality and CVD-related mortality contributed most to the ICER. CONCLUSION: Adding ezetimibe to the moderate-dose statin in secondary prevention for CVD is cost-effective, compared with the high-dose statin in the Chinese context whose low-density lipoprotein cholesterol (LDL-c) was not inadequately controlled by moderate-dose statin alone.

Generic atorvastatin and rosuvastatin in the South Korean market: time of introduction in relation to manufacturer characteristics.

Background: The competition for and market dynamics of generic medicines can be understood by analyzing manufacturers' behavior. In this study, we analyzed the various types of generic atorvastatin and rosuvastatin that were introduced onto the South Korean market from 2002 to 2018 and their corresponding manufacturers. Methods: Based on publicly available data, we selected drugs containing atorvastatin and rosuvastatin as active ingredients for the analysis. We calculated the time between the date of marketing approval for the first generic and that of the remaining generics. Then, we categorized manufacturers that marketed generics into first movers and latecomers. Results: We confirmed that many manufacturers have marketed generic drugs in South Korea and that manufacturers can be categorized as first movers and latecomers. Interestingly, latecomers account for a large portion of the manufacturers of generics, and they have entered the market steadily, even after the market matured with a number of manufacturers. Additionally, the characteristics of the manufacturers were closely related to manufacturers' behaviors in the market. Conclusions: The order-of-entry effect, which is commonly observed in other markets, is marginal in the South Korean market, and this phenomenon is mainly explained by the rare price competition among generic manufacturers.

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

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

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

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

The Cost-Benefit Balance of Statins in Hawai'i: A Moving Target.

Statins are lipid-lowering medications used for primary and secondary prevention of atherosclerotic disease and represent a substantial portion of drug costs in the United States. A better understanding of prescribing patterns and drug costs should lead to more rational utilization and help constrain health care expenditures in the United States. The 2013 Medicare Provider Utilization and Payment Data: Part D Prescriber Public Use File for the State of Hawai'i was analyzed. The number of prescriptions for statins, total annual cost, and daily cost were calculated by prescriber specialty and drug. Potential savings from substituting the highest-cost statin with lower-cost statins were calculated. Over 421,000 prescriptions for statins were provided to Medicare Part D beneficiaries in Hawai'i in 2013, which cost $17.6M. The three most commonly prescribed statins were simvastatin (33.4%), atorvastatin (33.4%), and lovastatin (13.9%). Although rosuvastatin comprised 5.4% of the total statin prescriptions, it represented 30.1% of the total cost of statins due to a higher daily cost ($5.53/day) compared to simvastatin ($0.25/day) and atorvastatin ($1.10/day). Cardiologists and general practitioners prescribed the highest percentage of rosuvastatin (8% each). Hypothetical substitution of rosuvastatin would have resulted in substantial annual cost savings (Simvastatin would have saved $1.3M for 25% substitution and $5.1M for 100% substitution, while atorvastatin would have saved $1.1M for 25% substitution and $4.3M for 100% substitution). Among Medicare Part D beneficiaries in Hawai'i, prescribing variation for statins between specialties were observed. Substitution of higher-cost with lower-cost statins may lead to substantial cost savings.

Using lower cost statins improves outcomes for normal cholesterol non-diabetic patients.

BACKGROUND: The American College of Cardiology recommends considering initiation of cholesterol-lowering therapy in normal cholesterol adults aged 45-70, who are either diabetic or have a 10 year atherosclerotic cardiovascular disease risk higher than 7.5%. Although this policy was shown to be cost-effective, the multi-billion dollar budget impact may limit the adoption, diffusion and overall clinical impact of this therapy. OBJECTIVES: We examined whether using a substantially lower cost statin (Simvastatin) in a much wider population, while accepting almost-as-good per-patient outcomes can provide better outcomes for the entire intended use population (IUP) under a pre-specified budget constraint. METHODS: We built a model to compare the outcomes on the entire IUP, and compared branded Rosuvastatin to Simvastatin. Outcomes measured were major adverse cardiovascular events (MACE): cardiovascular death, stroke, myocardial infarction, and hospitalization for revascularization or unstable angina. RESULTS: The branded Rosuvastatin alternative resulted in the prevention of 6,571 MACE compared to 311,698 MACE with Simvastatin, and 83,120 MACE with generic Rosuvastatin. CONCLUSIONS: Under budget constraints, using Simvastatin instead of branded Rosuvastatin resulted in a 47 fold increase of prevention of MACE for the entire IUP. These results should be considered while initiating statin therapy in this target population.

Impact of Cost Sharing on Therapeutic Substitution: The Story of Statins in 2006.

BACKGROUND: Cost sharing is widely used to encourage therapeutic substitution. This study aimed to examine the impact of increases in patient cost-sharing differentials for brand name and generic drugs on statin utilization on entry into the Medicare Part D coverage gap. METHOD AND RESULTS: Using 5% Medicare Chronic Condition Warehouse files from 2006, this quasi-experimental study examined patients with hyperlipidemia who filled prescriptions for atorvastatin or rosuvastatin between January and March 2006. Propensity score matching and difference-in-difference regressions were used to compare changes in statin utilization for the study group (patients who were not eligible for low-income subsidies [non-LIS] and had generic-only gap coverage) to those of a control group (LIS patients who faced the same cost sharing before and during the Part D coverage gap). In the final sample, 801 patients in the study group were matched to 801 patients in the control group. We found that, compared to the control group, the study group had a larger decline in any monthly brand-name statin use (-0.24 30-day fills, P<0.001). This was only partially offset by increased monthly generic statin use (+0.06 30-day fill, P<0.001), with an overall drop in any monthly statin use (-0.18 30-day fills, P<0.001). Overall adherence with statins declined (OR 0.81, P<0.001), and statin discontinuation increased (OR 1.62, P<0.001) in the study group as compared to the control group. CONCLUSIONS: Increases in cost-sharing differentials for brand name and generic drugs on coverage gap entry were associated with discontinuation of statins in Medicare Part D patients with hyperlipidemia.

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.

Cost-effectiveness of adding ezetimibe to atorvastatin vs switching to rosuvastatin therapy in Portugal.

BACKGROUND: Statin monotherapy is the mainstay of low-density lipoprotein cholesterol (LDL-C) management for high cardiovascular risk patients in Portugal; however, several therapeutic options are available and predicted to have different clinical and economic impacts. The aim of this study was to evaluate the cost-effectiveness of adding ezetimibe 10 mg (EZ10) to atorvastatin 10 or 20 mg (A10/20) vs switching to rosuvastatin 10 or 20 mg (R10/20) in Portuguese patients with coronary heart disease (CHD) and/or diabetes who are currently above the LDL-C goal. METHODS: A Markov model was used to describe CHD disease progression and the lifetime costs and utilities associated with each disease state were used to estimate the gains in life-years and quality-adjusted life-years (QALYs), as well as the incremental cost-effectiveness ratio (ICER), of the two treatment regimens. Model inputs, such as age, gender, and prevalence of cardiovascular risk factors of the dyslipidemic Portuguese patients were obtained from the Portuguese cohort of the Dyslipidemia International Study (DYSIS). The efficacy of each treatment regimen, the cost of drugs and of treating CHD events, and the utilities for each disease state were derived from published sources. RESULTS: The estimated lifetime discounted number of QALYs gained by patients treated with A10/20 was 8.70, while in those switching to R10/20 it was 8.81 and in those adding EZ10 it was 8.93. Discounted total health costs were estimated to be €11,131 for A10/20, but €14,511 and €16,571 for R10/20 and A10/20 + EZ10, respectively. The ICER of adding ezetimibe vs switching to rosuvastatin was €16,465/QALY. Based on the Portuguese cost-effectiveness willingness-to-pay threshold of €30,000/QALY, adding ezetimibe vs switching to rosuvastatin would be a cost-effective use of resources in Portugal. Sensitivity analyses in patients with differing clinical histories (CHD or diabetes or both) yielded similar values, with no ICER over €30,000/QALY. CONCLUSIONS: From the perspective of the National Health Service, prescribing ezetimibe to high cardiovascular risk patients being treated with atorvastatin vs switching them to rosuvastatin is projected to be a cost-effective use of resources in Portugal.

[Cost-effectiveness of rosuvastatin versus simvastatin, atorvastatin and pitavastatin in patients with high and very high cardiovascular risk in Spain]. / Coste-efectividad de rosuvastatina frente a simvastatina, atorvastatina y pitavastatina en pacientes con riesgo cardiovascular alto y muy alto en España.

INTRODUCTION AND OBJECTIVES: To estimate the cost-effectiveness of rosuvastatin versus simvastatin, atorvastatin and pitavastatin in Spain, according to the European guidelines for the treatment of dyslipidemias in patients with high and very high cardiovascular risk. METHODS: A Markov long-term cost-effectiveness model of rosuvastatin versus simvastatin, atorvastatin and pitavastatin in patients with high and very high cardiovascular risk defined according to 5 factors (sex, age, smoking habit, baseline cholesterol level, and systolic blood pressure) using the SCORE system. The incremental cost-effectiveness ratio is expressed in euros per quality adjusted life years and is calculated according to the perspective of the Spanish National Health System. RESULTS: Rosuvastatin is associated with a greater health benefit than the other statins across the considered profiles. Rosuvastatin is cost-effective compared to simvastatin in patients with SCORE risk ≥8% in females and ≥6% in males, while between 5% and the indicated values its cost-effectiveness is conditional to the patient baseline c-LDL level. Rosuvastatin is more cost-effective versus atorvastatin in female profiles associated with a SCORE risk≥11% and male profiles with SCORE risk ≥10%. Rosuvastatin is superior versus pitavastatin in both female and male profiles with high and very high cardiovascular risk. CONCLUSIONS: Rosuvastatin is a cost-effective therapy in the treatment of hypercholesterolemia versus simvastatin, atorvastatin and pitavastatin, especially in specific profiles of patients with high and very high cardiovascular risk factors, according to the SCORE system, in Spain.

Quality and efficiency of statin prescribing across countries with a special focus on South Africa: findings and future implications.

INTRODUCTION: Statins are recommended first-line treatment for hyperlipidemia, with published studies suggesting limited differences between them. However, there are reports of under-dosing. South Africa has introduced measures to enhance generic utilization. Part one documents prescribed doses of statins in 2011. Part two determines the extent of generics versus originator and single-sourced statins in 2011 and their costs. RESULTS: Underdosing of simvastatin in 2011 with average prescribed dose of 23.7 mg; however, not for atorvastatin (20.91 mg) or rosuvastatin (15.02 mg). High utilization of generics versus originators at 93-99% for atorvastatin and simvastatin, with limited utilization of single-sourced statins (22% of total statins - defined daily dose basis), mirroring Netherlands, Sweden and UK. Generics priced 33-51% below originator prices. DISCUSSION: Opportunity to increase simvastatin dosing through education, prescribing targets and incentives. Opportunity to lower generic prices with generic simvastatin 96-98% below single-sourced prices in some European countries.