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.

Cost-effectiveness of statin therapy for vascular event prevention in adults with elevated C-reactive protein: implications of JUPITER.

OBJECTIVES: High-sensitivity C-reactive protein (hs-CRP) has been explored for use in predicting cardiovascular risk. The recent Justification for the Use of Statins in Primary Prevention: An Intervention Trial Evaluating Rosuvastatin (JUPITER) study found that statin therapy reduced cardiovascular events in those with low-density lipoprotein (LDL) cholesterol levels below current treatment thresholds (≤130 mg/dL, 3.4 = mmol/L), but with elevated hs-CRP levels (≥2.0 mg/L). This study examines the cost-effectiveness of statin treatment for individuals with elevated hs-CRP but normal LDL cholesterol. METHODS: A Markov decision-analytic model was conducted from the U.S. societal perspective. Data from JUPITER were used to estimate rates of myocardial infarction, angina and stroke. Statin costs were based on generic simvastatin 80 mg, equipotent to the rosuvastatin 20 mg dose used in JUPITER. Primary prevention was the focus and secondary prevention was not modeled explicitly. Quality-adjusted life-years (QALYs) were calculated using nationally representative preference-based utility weights. One-way sensitivity analyses and multivariate probabilistic sensitivity analysis were used to explore uncertainty in model parameters as well as estimate the likelihood of cost-effectiveness when all event rates, costs and utilities were drawn randomly from distributions reflecting uncertainty. RESULTS: Statin therapy cost $10,889/QALY for vascular event prevention in this population. Results were sensitive to the cost of statin treatment. Based on 10,000 simulations, statin therapy was cost-effective in 99.5% of simulations, using a willingness-to-pay threshold of $20,000/QALY, and 100% of simulations using a threshold of $50,000/QALY. CONCLUSIONS: Treatment with statins in patients with elevated hs-CRP but normal cholesterol appears to be cost-effective. Limitations of this study include the assumption that an equipotent dose of simvastatin resulted in the same risk reduction as rosuvastatin. Further, post-event states simulated the average experience of a patient. Continued statin use, subsequent events and/or heart failure were not explicitly modeled.

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.

Rosuvastatin in the management of hyperlipidemia.

BACKGROUND: Rosuvastatin is a new statin indicated to reduce elevated levels of total cholesterol, low-density lipoprotein cholesterol (LDL-C), and triglycerides and to increase levels of high-density lipoprotein cholesterol (HDL-C) in patients with primary hypercholesterolemia, mixed dyslipidemia, and homozygous familial hypercholesterolemia. OBJECTIVE: The purpose of this article was to review the pharmacology, clinical efficacy, and tolerability of rosuvastatin as monotherapy and combination therapy for patients with hyperlipidemia. METHODS: A literature review was conducted using the search term rosuvastatin to identify English-language peer-reviewed articles and abstracts in the MEDLINE and Current Contents databases (both 1966 to March 2004). Citations from available articles were reviewed for additional references, and selected information from the manufacturer was discussed. RESULTS: Rosuvastatin 10 to 40 mg/d reduced LDL-C by 43% to 63% (P < 0.05). Compared with other statins, rosuvastatin had the highest dose-to-dose potency in lowering LDL-C (reduction of 60% vs 50% with atorvastatin, 40% with simvastatin, 30% with pravastatin or lovastatin, and 20% with fluvastatin) and better efficacy in raising HDL-C (increase of approximately 10% vs approximately 5% with other statins; P < 0.05). Rosuvastatin enabled significantly more patients to achieve the National Cholesterol Education Program (NCEP) goals for LDL-C with lower doses (P < 0.05). Rosuvastatin was well tolerated. Incidences of myopathy and liver function test abnormalities were rare and comparable to those of other statins. Because it is not metabolized by the cytochrome P-450 enzymes, rosuvastatin had fewer clinically significant drug interactions compared with other statins. Studies to assess the effect of rosuvastatin on cardiovascular outcomes are ongoing. CONCLUSIONS: Clinical studies continue to demonstrate that achieving optimal levels of LDL-C is an important goal in reducing cardiovascular events. Recent evidence suggests the need for an even lower LDL-C goal than that being recommended by the NCEP Based on the studies included in this review, rosuvastatin may help patients achieve optimal goals early with lower dosages, thus reducing the need for dose titration or combination therapy.