Cost-Effectiveness of Simvastatin Plus Ezetimibe for Cardiovascular Prevention in Patients With a History of Acute Coronary Syndrome: Analysis of Results of the IMPROVE-IT Trial.

BACKGROUND: Simvastatin plus ezetimibe reduced the risk of cardiovascular events in the IMProved Reduction of Outcomes: Vytorin Efficacy International (IMPROVE-IT) study. The aim of this study is to investigate the cost-effectiveness of adding ezetimibe to simvastatin treatment for patients with ACS based on the recently completed IMPROVE-IT trial. METHODS: We constructed a Markov state-transition model to evaluate the costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness (ICER) associated with co-therapy compared with simvastatin alone from a health care perspective. We ran separate base-case analyses assuming a trial-length and longer term follow-up. One-way sensitivity analyses were used to explore uncertainty in model parameters. RESULTS: In the trial-length model, the ICERs compared with simvastatin alone were $114,400 per QALY for the combination therapy. In 5- and 10-year time horizons, the ICERs remained above the cost-effectiveness threshold of $50,000 per QALY. In the lifetime horizon model, The ICER was $45,046 per QALY for combination treatment compared with simvastatin alone. The combination therapy is cost-effective at an 80% decrease in the current branded simvastatin and ezetimibe cost. Probabilistic sensitivity analysis suggested simvastatin and ezetimibe co-therapy would be a cost-effective alternative to simvastatin monotherapy 60.7% of the time. CONCLUSIONS: In our trial-length, 5-year, and 10-year models, the co-therapy was not a cost-effective alternative; however, as follow-up was extended to lifetime, the co-therapy became a cost-effective treatment compared with the simvastatin monotherapy in patients with histories of ACS.

Simvastatin for patients with acute respiratory distress syndrome: long-term outcomes and cost-effectiveness from a randomised controlled trial.

BACKGROUND: Simvastatin therapy for patients with acute respiratory distress syndrome (ARDS) has been shown to be safe and associated with minimal adverse effects, but it does not improve clinical outcomes. The aim of this research was to report on mortality and cost-effectiveness of simvastatin in patients with ARDS at 12 months. METHODS: This was a cost-utility analysis alongside a multicentre, double-blind, randomised controlled trial carried out in the UK and Ireland. Five hundred and forty intubated and mechanically ventilated patients with ARDS were randomly assigned (1:1) to receive once-daily simvastatin (at a dose of 80 mg) or identical placebo tablets enterally for up to 28 days. RESULTS: Mortality was lower in the simvastatin group (31.8%, 95% confidence interval (CI) 26.1-37.5) compared to the placebo group (37.3%, 95% CI 31.6-43.0) at 12 months, although this was not significant. Simvastatin was associated with statistically significant quality-adjusted life year (QALY) gain (incremental QALYs 0.064, 95% CI 0.002-0.127) compared to placebo. Simvastatin was also less costly (incremental total costs -£3601, 95% CI -8061 to 859). At a willingness-to-pay threshold of £20,000 per QALY, the probability of simvastatin being cost-effective was 99%. Sensitivity analyses indicated that the results were robust to changes in methodological assumptions with the probability of cost-effectiveness never dropping below 90%. CONCLUSION: Simvastatin was found to be cost-effective for the treatment of ARDS, being associated with both a significant QALY gain and a cost saving. There was no significant reduction in mortality at 12 months, TRIAL REGISTRATION: ISRCTN, 88244364. Registered 26 November 2010.

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.

Cost-effectiveness of the polypill versus risk assessment for prevention of cardiovascular disease.

OBJECTIVE: There is an international trend towards recommending medication to prevent cardiovascular disease (CVD) in individuals at increasingly lower cardiovascular risk. We assessed the cost-effectiveness of a population approach with a polypill including a statin (simvastatin 20 mg) and three antihypertensive agents (amlodipine 2.5 mg, losartan 25 mg and hydrochlorothiazide 12.5 mg) and periodic risk assessment with different risk thresholds. METHODS: We developed a microsimulation model for lifetime predictions of CVD events, diabetes, and death in 259 146 asymptomatic UK Biobank participants aged 40-69 years. We assessed incremental costs and quality-adjusted life-years (QALYs) for polypill scenarios with the same combination of agents and doses but differing for starting age, and periodic risk assessment with 10-year CVD risk thresholds of 10% and 20%. RESULTS: Restrictive risk assessment, in which statins and antihypertensives were prescribed when risk exceeded 20%, was the optimal strategy gaining 123 QALYs (95% credible interval (CI) -173 to 387) per 10 000 individuals at an extra cost of £1.45 million (95% CI 0.89 to 1.94) as compared with current practice. Although less restrictive risk assessment and polypill scenarios prevented more CVD events and attained larger survival gains, these benefits were offset by the additional costs and disutility of daily medication use. Lowering the risk threshold for prescription of statins to 10% was economically unattractive, costing £40 000 per QALY gained. Starting the polypill from age 60 onwards became the most cost-effective scenario when annual drug prices were reduced below £240. All polypill scenarios would save costs at prices below £50. CONCLUSIONS: Periodic risk assessment using lower risk thresholds is unlikely to be cost-effective. The polypill would become cost-effective if drug prices were reduced.

Cost-benefit analysis of the polypill in the primary prevention of myocardial infarction and stroke.

The primary prevention of cardiovascular disease is a public health priority. To assess the costs and benefits of a Polypill Prevention Programme using a daily 4-component polypill from age 50 in the UK, we determined the life years gained without a first myocardial infarction (MI) or stroke, together with the total service cost (or saving) and the net cost (or saving) per year of life gained without a first MI or stroke. This was estimated on the basis of a 50 % uptake and a previously published 83 % treatment adherence. The total years of life gained without a first MI or stroke in a mature programme is 990,000 each year in the UK. If the cost of the Polypill Prevention Programme were £1 per person per day, the total cost would be £4.76 bn and, given the savings (at 2014 prices) of £2.65 bn arising from the disease prevented, there would be a net cost of £2.11 bn representing a net cost per year of life gained without a first MI or stroke of £2120. The results are robust to sensitivity analyses. A national Polypill Prevention Programme would have a substantial effect in preventing MIs and strokes and be cost-effective.

Cost-effectiveness of Simvastatin plus Ezetimibe for Cardiovascular Prevention in CKD: Results of the Study of Heart and Renal Protection (SHARP).

BACKGROUND: Simvastatin, 20mg, plus ezetimibe, 10mg, daily (simvastatin plus ezetimibe) reduced major atherosclerotic events in patients with moderate to severe chronic kidney disease (CKD) in the Study of Heart and Renal Protection (SHARP), but its cost-effectiveness is unknown. STUDY DESIGN: Cost-effectiveness of simvastatin plus ezetimibe in SHARP, a randomized controlled trial. SETTING & POPULATION: 9,270 patients with CKD randomly assigned to simvastatin plus ezetimibe versus placebo; participants in categories by 5-year cardiovascular risk (low, <10%; medium, 10%-<20%; or high, ≥20%) and CKD stage (3, 4, 5 not on dialysis, or on dialysis therapy). MODEL, PERSPECTIVE, & TIMELINE: Assessment during SHARP follow-up from the UK perspective; long-term projections. INTERVENTION: Simvastatin plus ezetimibe (2015 UK £1.19 per day) during 4.9 years' median follow-up in SHARP; scenario analyses with high-intensity statin regimens (2015 UK £0.05-£1.06 per day). OUTCOMES: Additional health care costs per major atherosclerotic event avoided and per quality-adjusted life-year (QALY) gained. RESULTS: In SHARP, the proportional reductions per 1mmol/L of low-density lipoprotein (LDL) cholesterol reduction with simvastatin plus ezetimibe in all major atherosclerotic events of 20% (95% CI, 6%-32%) and in the costs of vascular hospital episodes of 17% (95% CI, 4%-28%) were similar across participant categories by cardiovascular risk and CKD stage. The 5-year reduction in major atherosclerotic events per 1,000 participants ranged from 10 in low-risk to 58 in high-risk patients and from 28 in CKD stage 3 to 36 in patients on dialysis therapy. The net cost per major atherosclerotic event avoided with simvastatin plus ezetimibe compared to no LDL-lowering regimen ranged from £157,060 in patients at low risk to £15,230 in those at high risk (£30,500-£39,600 per QALY); and from £47,280 in CKD stage 3 to £28,180 in patients on dialysis therapy (£13,000-£43,300 per QALY). In scenario analyses, generic high-intensity statin regimens were estimated to yield similar benefits at substantially lower cost. LIMITATIONS: High-intensity statin-alone regimens were not studied in SHARP. CONCLUSIONS: Simvastatin plus ezetimibe prevented atherosclerotic events in SHARP, but other less costly statin regimens are likely to be more cost-effective for reducing cardiovascular risk in CKD.

[Choosing wisely when prescribing statins]. / Verstandig kiezen bij het voorschrijven van statinen.

The Dutch campaign 'Verstandig kiezen', based on the American programme 'Choosing wisely', aims to improve quality in healthcare, with attention to cost control. The 'Choosing wisely'-based programme can be applied in the choice of a statin. Atorvastatin and rosuvastatin are regarded as equal choices in various guidelines regarding cardiovascular risk management. Generic atorvastatin is available, and is approximately 25 times cheaper than rosuvastatin in almost equipotent doses. Rosuvastatin provides a greater LDL reduction than atorvastatin. Patient LDL targets can usually be achieved with atorvastatin, and rosuvastatin is not needed. At group level, there are no relevant differences in adverse-events profile between both statins. Atorvastatin and rosuvastatin do have different pharmacokinetic interactions. When changing medication, good provision of information is a prerequisite for patient satisfaction and compliance. We advise use of atorvastatin instead of rosuvastatin as drug of choice when the LDL target is not reached using simvastatin. However, under specific conditions, rosuvastatin should be the treatment of choice. Efficacy and adverse effects should then be evaluated at individual patient level.

The impact of changes in national prescribing conditions for statins on their public expenditure and utilization in the Czech Republic 1997-2013.

OBJECTIVES: In the Czech Republic (CZ) extensive price regulation and prescribing conditions are common instruments often employed with new drugs. Since the introduction of statins onto the market in 1990s the originally strict conditions gradually relaxed while the prescription rates and public costs were rising. The aim was to analyze long-term utilization trends of statins, changes in their reimbursement prices and prescribing conditions, and the evolution of the market. METHODS: From January 1997 to December 2013 statin use was measured in terms of defined daily doses per 1000 insured per day (DDD/TID). The prescription-based database of the General Health Insurance Company of the Czech Republic in 1997 covering 7825,216 inhabitants, i.e. 76% of CZ population, was used as the administrative data source. Also the overall expenditure, unit prices, and reimbursement criteria were analyzed. RESULTS: Between 1997 and 2013 the utilization of statins rose from 2 to 96 DDD/TID while the expenditure rose 5.5-fold. The rise of prescription for each molecule was always observed after the liberation of the prescribing criteria. In the study period reimbursement prices of simvastatin and atorvastatin gradually decreased to just 5% of their initial values. CONCLUSIONS: The rising consumption of statins in CZ clearly corresponds in time with the liberation of prescribing conditions allowing for prescription by general practitioners and with the introduction of generics accompanied by a swift and repeated reimbursement price cuts.

[LDL cholesterol lowering therapy: no target value but personalised treatment]. / LDL-cholesterolverlagende therapie: geen streefwaarde maar behandeling op maat.

We previously recommended that LDL cholesterol lowering therapy be based on the risk for (recurrent) coronary events, rather than on arbitrary targets for serum LDL cholesterol concentration. We also recommended refraining from therapy with ezetimibe until its efficacy in preventing cardiovascular events had been documented. At the American Heart Association scientific sessions 2014 the results of the IMPROVE-IT study were reported. In this large, randomised trial, a modest benefit of the combination of simvastatin plus ezetimibe over simvastatin alone was reported after 7 years of treatment. The efficacy of such combination therapy was similar to the efficacy of high-dose statin therapy, while the combination therapy is much more expensive. Comparing the efficacy and costs of different preventive therapies, we recommend first prescribing aspirin and a moderate dose of statin, secondly an ACE inhibitor. A high-dose statin should be considered in high-risk patients. The combination of simvastatin and ezetimibe should be prescribed only in high-risk patients (e.g. diabetics after myocardial infarction) who do not tolerate high-dose statins.

On the hypothetical universal use of statins in primary prevention: an observational analysis on low-risk patients and economic consequences of a potential wide prescription rate.

PURPOSE: Recent guidelines expand indications for statins. However, research on practical economic feasibility and cost-effectiveness in low-risk people is lacking. We aimed to describe the incidence of cardiovascular events (CVE), their total direct costs and the hypothetical effects of wide provision of statins on those rates and expenditures. METHODS: We conducted a population-based cohort study using administrative data among low risk individuals. Estimators of effects of statins were taken from Cholesterol Treatment trialist metaanalysis and from Heart Protection Study trial. Two statin prices were used for analyses: National Italian Health System (€ 0.36) and the International Drug Price Indicator (€ 0.021). RESULTS: Overall, 920,067 persons at low risk were identified and 14,849 CVE were registered (incidence rate 27.3 per 10,000 person-years). Direct costs for hospitalizations for CVE were 143 M €. Universal provision of statins would result in a significant decrease in CVE rates, from 27.3 to 17.5 per 10,000 person-years (PY) (95% confidence interval (CI): 15.8-19.4). Universal prescription of simvastatin 20 mg would cost 802 M €. Otherwise, provision of simvastatin at International Drug Price Indicator's prices would be both clinically effective and cost saving in men older than age 44 (observed expenditures 120 M €, expected 97.4 M €) but not in women (observed expenditures 22.7 M €, expected 36.5 M €). CONCLUSIONS: Among a low-risk population, hypothetical universal provision of low-cost simvastatin to men over 44 years could be both clinically effective and a cost-saving strategy.

[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.

Cost-Effectiveness of High, Moderate and Low-Dose Statins in the Prevention of Vascular Events in the Brazilian Public Health System / Efetividade de Estatinas em Dose Alta, Moderada e Baixa na Prevenção de Eventos Vasculares no SUS

Background: Statins have proven efficacy in the reduction of cardiovascular events, but the financial impact of its widespread use can be substantial. Objective: To conduct a cost-effectiveness analysis of three statin dosing schemes in the Brazilian Unified National Health System (SUS) perspective. Methods: We developed a Markov model to evaluate the incremental cost-effectiveness ratios (ICERs) of low, intermediate and high intensity dose regimens in secondary and four primary scenarios (5%, 10%, 15% and 20% ten-year risk) of prevention of cardiovascular events. Regimens with expected low-density lipoprotein cholesterol reduction below 30% (e.g. simvastatin 10mg) were considered as low dose; between 30-40%, (atorvastatin 10mg, simvastatin 40mg), intermediate dose; and above 40% (atorvastatin 20-80mg, rosuvastatin 20mg), high-dose statins. Effectiveness data were obtained from a systematic review with 136,000 patients. National data were used to estimate utilities and costs (expressed as International Dollars - Int$). A willingness-to-pay (WTP) threshold equal to the Brazilian gross domestic product per capita (circa Int$11,770) was applied. Results: Low dose was dominated by extension in the primary prevention scenarios. In the five scenarios, the ICER of intermediate dose was below Int$10,000 per QALY. The ICER of the high versus intermediate dose comparison was above Int$27,000 per QALY in all scenarios. In the cost-effectiveness acceptability curves, intermediate dose had a probability above 50% of being cost-effective with ICERs between Int$ 9,000-20,000 per QALY in all scenarios. Conclusions: Considering a reasonable WTP threshold, intermediate dose statin therapy is economically attractive, and should be a priority intervention in prevention of cardiovascular events in Brazil. .

Fundamento: Estatinas tem eficácia comprovada na redução de eventos cardiovasculares, mas o impacto financeiro de seu uso disseminado pode ser substancial. Objetivo: Conduzir análise de custo-efetividade de três esquemas de doses de estatinas na perspectiva do SUS. Métodos: Foi desenvolvido modelo de Markov para avaliar a razão de custo-efetividade incremental (RCEI) de regimes de dose baixa, intermediária e alta, em prevenção secundária e quatro cenários de prevenção primária (risco em 10 anos de 5%, 10%, 15% e 20%). Regimes com redução de LDL abaixo de 30% (ex: sinvastatina 10mg) foram considerados dose baixa; entre 30-40% (atorvastatina 10mg, sinvastatina 40mg), dose intermediária; e acima de 40% (atorvastatina 20-80 mg, rosuvastatina 20 mg), dose alta. Dados de efetividade foram obtidos de revisão sistemática com aproximadamente 136.000 pacientes. Dados nacionais foram usados para estimar utilidades e custos (expressos em dólares internacionais - Int$). Um limiar de disposição a pagar (LDP) igual ao produto interno bruto per capita nacional (aproximadamente Int$11.770) foi utilizado. Resultados: A dose baixa foi dominada por extensão nos cenários de prevenção primária. Nos cinco cenários, a RCEI da dose intermediária ficou abaixo de Int$10.000 por QALY. A RCEI de dose alta ficou acima de Int$27.000 por QALY em todos os cenários. Nas curvas de aceitabilidade de custo-efetividade, dose intermediária teve probabilidade de ser custo-efetiva acima de 50% com RCEIs entre Int$9.000-20.000 por QALY em todos os cenários. Conclusões: Considerando um LDP razoável, uso de estatinas em doses intermediárias é economicamente atrativo, e deveria ser intervenção prioritária na redução de eventos cardiovasculares no Brasil. .

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.

Cost-effectiveness of high, moderate and low-dose statins in the prevention of vascular events in the Brazilian public health system.

BACKGROUND: Statins have proven efficacy in the reduction of cardiovascular events, but the financial impact of its widespread use can be substantial. OBJECTIVE: To conduct a cost-effectiveness analysis of three statin dosing schemes in the Brazilian Unified National Health System (SUS) perspective. METHODS: We developed a Markov model to evaluate the incremental cost-effectiveness ratios (ICERs) of low, intermediate and high intensity dose regimens in secondary and four primary scenarios (5%, 10%, 15% and 20% ten-year risk) of prevention of cardiovascular events. Regimens with expected low-density lipoprotein cholesterol reduction below 30% (e.g. simvastatin 10mg) were considered as low dose; between 30-40%, (atorvastatin 10mg, simvastatin 40 mg), intermediate dose; and above 40% (atorvastatin 20-80 mg, rosuvastatin 20mg), high-dose statins. Effectiveness data were obtained from a systematic review with 136,000 patients. National data were used to estimate utilities and costs (expressed as International Dollars - Int$). A willingness-to-pay (WTP) threshold equal to the Brazilian gross domestic product per capita (circa Int$11,770) was applied. RESULTS: Low dose was dominated by extension in the primary prevention scenarios. In the five scenarios, the ICER of intermediate dose was below Int$10,000 per QALY. The ICER of the high versus intermediate dose comparison was above Int$27,000 per QALY in all scenarios. In the cost-effectiveness acceptability curves, intermediate dose had a probability above 50% of being cost-effective with ICERs between Int$ 9,000-20,000 per QALY in all scenarios. CONCLUSIONS: Considering a reasonable WTP threshold, intermediate dose statin therapy is economically attractive, and should be a priority intervention in prevention of cardiovascular events in Brazil.

Cost-effectiveness and cost-utility analysis of OTC use of simvastatin 10 mg for the primary prevention of myocardial infarction in Iranian men.

BACKGROUND: Several clinical trials and meta-analyses have shown the advantageous effects of statins in populations with different levels of cardiovascular disease (CVD) risk. Considering the increasing cardiovascular risk among the Iranian population, the cost-effectiveness of the use of simvastatin 10 mg, as an Over-The-Counter (OTC) drug, for the primary prevention of myocardial infarction (MI) was evaluated in this modeling study, from the payer's perspective. The target population is a hypothetical cohort of 45-year CVD healthy men with an average (15%) 10-year CVD risk. METHODS: A semi-Markov model with a life-long time horizon was developed to evaluate the Cost-Utility-Analysis (CUA) and Cost-Effectiveness-Analysis (CEA) of the use of OTC simvastatin 10 mg compared to no-drug therapy. Two measures of benefits were used in the model; Quality-Adjusted-Life-Years (QALYs) for the CUA and Life-Years-Gained (LYG) for the CEA. To examine the robustness of the results, one-way sensitivity analysis and probabilistic sensitivity analysis were applied to the model. RESULTS: For the base-case scenario with a discount rate of 0% the estimated ICERs were 1113 USD/QALY and 935USD/LYG per patient (using governmental tariffs). No threshold has been determined in Iran for the cost-effectiveness of health-related interventions. However, according to the recommendation of WHO, this intervention can be considered highly cost-effective as its ICER is far less than the reported GDP per capita for Iran by World bank in 2013 ($4763). CONCLUSIONS: This modeling study showed that the use of an OTC low dose statin (simvastatin 10 mg) for the primary prevention of myocardial infarction (MI) in 45-year men with a 10-year CVD risk of 15% could be considered highly cost-effective in Iran, as it meets the WHO threshold of the annual GDP per capita ($4763).

[Rhabdomyolysis and severe hepatotoxicity due to a drug-drug interaction between ritonavir and simvastatin. Could we use the most cost-effective statin in all human immunodeficiency virus-infected patients?]. / Rabdomiólisis y hepatotoxicidad grave por interacción entre ritonavir y simvastatina. ¿Puede emplearse la estatina más coste-efectiva en todos los pacientes infectados por el virus de la inmunodeficiencia humana?

INTRODUCTION: Drugs like statins may induce rhabdomyolysis. Simvastatin and lovastatin have a high hepatic metabolism and their potential toxicity could be increased by interactions with other drugs that reduce their metabolism. PATIENTS AND METHODS: A case-report is presented of an HIV-infected patient treated with antiretroviral drugs who developed a rhabdomyolysis-induced renal failure and liver toxicity when simvastatin was substituted for atorvastatin. A literature review is also presented. RESULTS: The patient required hospital admission and showed a favorable response after hydration and urine alkalinization. There were 4 additional cases published of which there was one death. CONCLUSIONS: Drug-drug interactions can increase the risk of statin induced rhabdomyolysis. In order to evaluate them properly, physicians at all levels of clinical care should be aware of all drugs prescribed to their patients and the contraindicated combinations.

Trends in statin consumption and cardiovascular mortality in Croatia 2004-2012.

Prescribing of statins showed an increasing trend in all developed countries, during the last two decades. The aim of this study was to research the trends in statin consumption in the period from 2004 to 2012 as well as trends of cardiovascular mortality during the 1990 to 2012 period, and to compare them between Croatia and several neighbouring countries. Data on statin expenditures and consumption expresed in defined daily doses per 1000 inhabitants per day (DDD/TID), were taken from annual reports of Croatian Agency for Medicinal Products and Medical Devices (HALMED). Data on crude mortality rates and standardized cardiovascular mortality rates, were taken from the Croatian Health Statistics Yearbooks. The utilization of statins increased by 196.7% during the observed period, with the highest consumption of atorvastatin and simvastatin. Financial expenditure of statins expanded at much faster rate in comparison with overall drug costs. Cardiovascular mortality rates decreased slightly, while maintaining higher level in comparison with some neighbouring countries.

Evolutions in both co-payment and generic market share for common medication in the Belgian reference pricing system.

BACKGROUND: In Belgium, a co-insurance system is applied in which patients pay a portion of the cost for medicines, called co-payment. Co-payment is intended to make pharmaceutical consumers more responsible, increase solidarity, and avoid or reduce moral hazards. OBJECTIVE: Our objective was to study the possible influence of co-payment on sales volume and generic market share in two commonly used medicine groups: cholesterol-lowering medication [statins (HMG-CoA reductase inhibitors) and fibrates] and acid-blocking agents (proton pump inhibitors and histamine H2 receptor antagonists). METHODS AND DATA: The data were extracted from the Pharmanet database, which covers pharmaceutical consumption in all Belgian ambulatory pharmacies. First, the proportion of sales volume and costs of generic products were modelled over time for the two medicine groups. Second, we investigated the relation between co-payment and contribution by the national insurance agency using change-point linear mixed models. RESULTS: The change-point analysis suggested several influential events. First, the generic market share in total sales volume was negatively influenced by the abolishment of the distinction in the maximum co-payment level for name brands and generics in 2001. Second, relaxation of the reimbursement conditions for generic omeprazole stimulated generic sales volume in 2004. Finally, an increase in co-payment for generic omeprazole was associated with a significant decrease in omeprazole sales volume in 2005. The observational analysis demonstrated several changes over time. First, the co-payment amounts for name-brand and generic drugs converged in the observed time period for both medicine groups under study. Second, the proportion of co-payment for the total cost of simvastatin and omeprazole increased over time for small packages, and more so for generic than for name-brand products. For omeprazole, both the proportion and the amount of co-payment increased over time. Third, over time the prescription of small packages shifted to an emphasis on larger packages. CONCLUSIONS: As maximum co-payment levels decreased over time, they overruled the reference pricing system in Belgium. The changes in co-payment share over time also significantly affected sales volume, but whether physicians or patients are the decisive actors on the demand side of pharmaceutical consumption remains unclear.

Evidence based policy decisions through a Bayesian approach: the case of a statin appraisal in The Netherlands.

It has often been suggested that Bayesian statistics is more congenial to the informational needs of policy makers than the standard frequentist methods. In order to illustrate this claim, we use both a Bayesian and a frequentist approach for revisiting a recommendation by the Dutch National Health Insurance Board that for all patients requiring lipid reduction, the cheapest alternative (Simvastatin) should be prescribed. We investigate whether Simvastatin and Atorvastatin, the most commonly used alternative, can be considered equivalent in terms of lipid control for patients with heterozygous familial hypercholesterolemia. Priors were elicited from GPs, cardiologists and internists. A systematic review for studies comparing Simvastatin and Atorvastatin was performed. The data from these studies were combined with the priors in a Bayesian meta-analysis. For comparability a frequentist meta-analysis was also performed. The two approaches lead to similar point estimates and 95% intervals. However, the Bayesian outcomes are easier to understand and interpret, and our Bayesian analysis leads to additional outcomes that would have more direct pertinence for policy makers, and which could help them to assess what the data have to say about the questions that are most relevant to the problems they face.