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. .

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.

[Analysis of cost-effectiveness of simvastatin versus atorvastatin in the secondary prevention of cardiovascular events within the Brazilian public healthcare system]. / Análise de custo-efetividade da sinvastatina versus atorvastatina na prevenção secundária de eventos cardiovasculares no Sistema Único de Saúde Brasileiro.

OBJECTIVE: The objective of this study is to perform an economic evaluation analyzing the treatment with atorvastatin and simvastatin in comparison to placebo treatment, within the Brazilian Public Healthcare System (SUS) scenario, for patients with high risk of cardiovascular disease; analyzing if the additional cost related to statin treatment is justified by the clinical benefits expected, in terms of cardiovascular event and mortality reduction. METHODS: Cardiovascular event risk and mortality risk were used as outcomes. Statin efficacy at LDL-c and cardiovascular events levels lowering data was obtained from a systematic review of literature. A decision analytic model was developed to perform a cost-effectiveness analysis comparing atorvastatin 10mg/day and simvastatin 40 mg/day to placebo treatment in patients with dyslipidemia in Brazil. The target population of this study was a hypothetic cohort of men and women with a mean age of 50 years old and high risk of cardiovascular disease. The model includes only direct costs obtained from Ambulatory and Hospital Information System and Price Database of Brazilian Ministry of Health. The comparative cost-effectiveness analysis itself was done through Excel spreadsheets covering a 5 -years time horizon. RESULTS: The result shows that atorvastatin 10mg/day in comparison to placebo has higher cost with higher effectiveness in the time horizon of 5 years (Incremental Cost Effectiveness Ratio of R$ 433.065,05 per life year gained). In this scenario atorvastatin is not cost effective in comparison to placebo. The simvastatin 40 mg/day appears to be a strategy with lower cost and higher effectiveness in comparison to placebo, in the time horizon analyzed (5 years). In the multivariate probabilistic sensitivity analysis, simvastatin showed 53% of the results in the quadrant with greater effectiveness and lower cost. CONCLUSIONS: This study is an important tool for public decision makers. The study can be used in the decision process of increasing cardiovascular disease treatment access with budgetary sustainability for Ministry of Health. In comparison to placebo, the results show that sinvastatin is a cost saving strategy while atorvastatin is not cost effective.

Impact of restricted reimbursement on the use of statins in Finland: a register-based study.

OBJECTIVES: New and expensive medicines are a driving force behind growth in medicine costs, and policies promoting use of less expensive products have been widely introduced. This study investigated the short-term consequences of the restricted reimbursement of expensive statins (atorvastatin and rosuvastatin) on the use of statins in Finland. METHODS: Data on patients purchasing atorvastatin, rosuvastatin, or simvastatin in 2002-2007 were retrieved from the nationwide Prescription Register. Outcome measures included the time trend in the numbers of purchasers and initiators of different statins, the morbidities of new users before and after the new policy, and the proportion of users of expensive statins switching to other statins. RESULTS: After the restriction, the numbers of purchasers of atorvastatin and rosuvastatin dropped, and atorvastatin and rosuvastatin were seldom prescribed as first-line therapy. Before the restriction, 20.9% of new users of atorvastatin and 18.4% of those of rosuvastatin had either coronary artery disease or familial hyperlipidemia. After the restriction the corresponding figures were 28.7% and 26.8%. After the restriction new users of atorvastatin and rosuvastatin were also more likely to use other cardiovascular medicines or antidiabetics or to have previous statin purchases. A total of 57.6% of those using atorvastatin and 49.2% of those using rosuvastatin before the restriction switched to a less expensive statin. CONCLUSIONS: Restricted reimbursement of expensive statins decreased their use. It seems that after the policy new statin treatments have channeled appropriately. Although it is likely that the cost-containment aim of the policy was reached, health and long-term effects are not known.

[Analysis of the budget impact for the Spanish National Health System of the fixed combination of amlodipine 5 or 10mg and atorvastatin 10mg]. / Análisis del impacto presupuestario para el Sistema Nacional de Salud de la combinación fija de amlodipino 5 o 10mg y atorvastatina 10mg.

OBJECTIVE: To carry out a Budget Impact Analysis (BIA) of the inclusion of the administration, within the Spanish National Health System (SNS), of the fixed combination (FC) of amlodipine 5 or 10mg and atorvastatin 10mg for approved indications. MATERIALS AND METHODS: A BIA was carried out from the SNS perspective for a 3 year period (2009-2011). A tree type decision model was designed (tree of patients), based on epidemiological data and scientific literature, to estimate the hypertensive population that could be treated with a FC. The total per annum BIA was calculated by attributing the retail price- VAT of the FC to the number of patients to be treated, and deducting the cost of the treatment for hypertension that was replaced and the updated average cost per patient of cardiovascular events (CVEs) prevented by the use of the FC by the SNS during the period of study. RESULTS: The patient population susceptible to treatment with the FC was 51,104 patients (1(st) year), with a growth rate of between 1-2% over the following years, which means an annual cost (euro) of 15.9M (2009), 19.9M (2010) and 24.1M (2011), with a total of 60.0M. The BIA was compensated showing negative impact values for the SNS when the cost of replaced antihypertensive treatment and prevented CVEs was deducted, with savings of euro69.9M over 3 years. CONCLUSION: The BIA of a FC of atorvastatin and amlodipine shows that the use of this medication for approved indications could generate net savings for the SNS of euro9.9M for the period 2009-2011.

[Cost-effectiveness of managing familial hypercholesterolemia using atorvastatin-based preventive therapy]. / Coste-efectividad del manejo de la hipercolesterolemia familiar con estrategias de tratamiento preventivo basadas en atorvastatina.

INTRODUCTION AND OBJECTIVES: A cost-effectiveness model was developed to evaluate the efficiency of different preventive strategies in familial hypercholesterolemia (FH) in comparison with routine clinical practice (CP): atorvastatin monotherapy, 40 mg (A40) or 80 mg (A80, and atorvastatin combined with ezetimibe, 10 mg (A40+E10 or A80+E10). METHODS: A longitudinal population model with a time horizon for life-expectancy was developed within the context of the Spanish public healthcare system. Life tables for the Spanish population (2002) were modified using the standardized mortality rate for individuals with FH. Effectiveness was expressed in life-years gained (LYG), after taking into account reductions for risk (ie, Framingham risk score) and cardiovascular mortality. The costs (in 2005 terms) of the intervention (CI) and care (CC) were discounted at 6%, while effects were discounted at 3%. RESULTS: Routine CP, based on the Spanish FH registry: 1.97 LYG per patient vs. no treatment; CI euro5321, CC euro23,389. A40: 2.59 LYG; reduction in CC compared with CP 4.5%; total costs (TC) euro30 569. A80: 2.75 LYG; reduction in CC 6.4%; TC euro30 133. A40+E10: 3.38 LYG; reduction in CC 14.3%; TC euro36 104. A80+E10: 3.62 LYG; reduction in CC 17.6%; TC euro35 317. From most to least efficient strategy, the incremental cost-effectiveness per LYG compared with CP was: a) A80: euro1821; b) A40: euro3012; c) A80+E10: euro4021, and d) A40+E10: euro5250. CONCLUSIONS: Preventive treatment of FH with atorvastatin was cost-effective. The greatest cost-effectiveness was obtained with atorvastatin monotherapy, 80 mg. The addition of ezetimibe could produce further benefits at an acceptable incremental cost.

Eficácia da atorvastatina sem administração diária / Efficacy of atorvastatin when not administered daily

FUNDAMENTO: As estatinas têm larga utilização por reduzirem eventos cardíacos. Indicadas para uso diário, no entanto alguns a utilizam em dias alternados, principalmente visando diminuição de custos. OBJETIVO: Avaliar a eficácia da atorvastatina sem administração diária sobre os níveis de LDL-colesterol (LDL-C) e a redução dos custos. MÉTODOS: Foram avaliados 100 pacientes (P) hipercolesterolêmicos em prevenção primária (PP) e secundária (PS). Após período de dieta de 12 semanas iniciou-se atorvastatina 10 mg por dia. Após seis semanas foi dosado o LDL-C, e se níveis <80 ou <104 mg/dl conforme PS e PP, respectivamente, foi feita subtração de duas tomadas de atorvastatina da semana. Caso LDL-C continuasse <80 ou <104 mg/dl permitiria novo ajuste para três vezes na semana, sendo feita última dosagem após seis semanas. A variação porcentual de custos foi a forma de apreciar a economia. RESULTADOS: Em 47 P, dos 52 desse grupo, observou-se redução de LDL-C de 32 por cento, permanecendo com atorvastatina diária. Quarenta e um ficaram até o final do estudo e tiveram redução da posologia semanal. Em 25 P, a medicação foi administrada três vezes por semana e, em 16, cinco vezes por semana, exibindo redução de LDL-C de 42,4 por cento e 46,1 por cento, respectivamente. Sobre custos, um dos grupos teve despesa mensal de R$ 106,65 reduzido para R$ 74,65, e outro grupo, o gasto de R$ 106,65 foi reduzido a R$ 53,33. CONCLUSÃO: Os resultados sugerem que é possível administrar a atorvastatina de forma não-diária e observou-se redução dos custos entre 30 por cento e 50 por cento.

BACKGROUND: Statins are widely used because they reduce cardiac events. Although they are indicated for daily use, some doctorsgive prescriptions for every other day, mainly with the purpose of reducing costs. OBJECTIVE: To evaluate the efficacy of atorvastatin, when not administered everyday, on LDL-cholesterol (LDL-C) levels, and also to evaluate cost reduction. METHODS: A total of 100 patients with hypercholesterolemia in primary (PP) and secondary prevention (SP) were assessed. After a 12-week diet period, atorvastatin was initiated at a dose of 10 mg per day. After six weeks, LDL-C was determined, and if the levels were <80 or <104 mg/dL for SP and PP, respectively, two atorvastatin doses were subtracted per week. If LDL-C remained <80 or <104 mg/dL, a further reduction to three times a week was allowed, and the last determination was performed after six more weeks. The percentage variation in costs was the parameter to evaluate the saving. RESULTS: In 47 out of the 52 patients of this group, a reduction by 32 percent in LDL-C was observed, and daily atorvastatin was maintained. Forty one patients remained throughout the study and had their weekly dosage reduced. In 25 patients the medication was administered three times a week, and in 16, five times a week, with reductions of 42.4 percent and 46.1 percent in LDL-C, respectively. As regards costs, one of the groups had their monthly expense reduced from R$ 106.65 to R$ 74.65, and the other group from R$ 106.65 to R$ 53.33. CONCLUSION: The results suggest that atorvastatin may be administered on a non-daily basis. A cost reduction between 30 percent and 50 percent was also observed.

The pharmaco-economics of peri-operative statin therapy.

We analysed the pharmaco-economics of the prospective peri-operative studies of statin administration for major elective vascular surgery, using the NHS reference costs for 2004. This analysis suggests that peri-operative statin therapy for patients undergoing vascular surgery may present the most cost-effective use of statin therapy yet described, with a number-needed-to-treat of 15 and almost 60% of the total cost of atorvastatin therapy recovered through a reduction in peri-operative adverse events.

A pharmacoeconomic evaluation of the effects of atorvastatin on early recurrent ischemic events in acute coronary syndromes in Spain.

To determine the 16-week health economic outcomes of short-term, intensive lipid-lowering therapy with atorvastatin in patients with acute coronary syndrome (ACS) using unit costs from Spain. The total expected cost per patient and the cost per inpatient event avoided were compared for patients on atorvastatin 80 mg daily versus placebo. The analysis was based on clinical outcome data from the MIRACL study. Clinical outcomes measured in this analysis included: death, cardiac arrest, nonfatal myocardial infarction (MI), fatal MI, angina pectoris, stroke, congestive heart failure (CHF), and surgical or percutaneous coronary revascularizations. Unit costs for outcomes were values using 2001 Diagnosis Related Group (DRG) costs in Spain. The cost of a follow-up visit was added to the cost of each outcome in both groups. In the atorvastatin group, monitoring costs were also added. All direct medical costs were taken from the perspective of the Spanish National Health System during a 16-week period. The hospital cost in the atorvastatin group was 1,921 per patient, compared to 1,853 in the placebo group. The incremental cost per patient in the atorvastatin group was 67.47, corresponding to a cost per inpatient event avoided of 1,760. The cost of atorvastatin for 16 weeks was 128. Forty-seven percent of this cost of atorvastatin was offset by the cost savings obtained through the reduction of number of events in the atorvastatin group. In Spain, the intensive short-term use of atorvastatin in patients with ACS has a favorable cost-effectiveness. The direct cost of the drug was largely offset by the associated reduction in costs for treating fewer cardiovascular events.

Italian drug policy: ethical aims of essential assistance levels.

In 2001 the Italian Government defined Essential Assistance Levels (LEA), which can be considered as an important step forward in the health care system. The Italian health care system would provide payment of essential and uniform aid services in order to safeguard many values such as human dignity, personal health, equal assistance and good health practices. The Ministry of Health has worked to rationalize the National Formulary and to define evaluation methods for drugs in order to choose what to reimburse without penalizing the rights of the individual and society. This paper describes how this job of rationalization was done and tries to illustrate the choices made in Italy by the use of two meaningful examples (statins and rivastigmine).