The Cost Effectiveness of Statin Therapies in Spain in 2010, after the Introduction of Generics and Reference Prices

Background

HMG-CoA reductase inhibitors (statins) are the first-line drugs for use in the reduction of low-density lipoprotein cholesterol (LDL-C) levels and prevention of coronary heart disease (CHD) in patients with hypercholesterolemia. Generic statins could change the cost effectiveness of statin therapies in Spain, and more population groups could be included in the recommendations for reduction of cholesterol levels based on cost effectiveness.

Objectives

The objectives of this study were: (i) to assess the cost effectiveness of available statins for the reduction of LDL-C levels in Spain in 2010, after the introduction of generics and reference prices; (ii) to assess the cost effectiveness of combination therapy using a statin plus cholestyramine or ezetimibe; and (iii) to estimate the mean cost per patient to achieve National Cholesterol Education Program (Adult Treatment Panel-III) therapeutic objectives.

Methods

The following treatments were evaluated: rosuvastatin 5–20mg/day; atorvastatin, simvastatin, and pravastatin 10–40mg/day; lovastatin and fluvastatin 20–80mg/day; and combination therapy with a statin plus either cholestyramine 12–24g/day or ezetimibe 10mg/day. The cost effectiveness was evaluated in terms of cost per percentage point reduction in LDL-C, comparing the annual treatment costs with the effectiveness in reducing LDL-C. Treatment costs included those for medications (2010 wholesale prices), control measures, and treatment of adverse drug effects. The effectiveness of statins was estimated by developing a meta-analysis of clinical trials published between 1993 and 2005 that met several inclusion criteria. Average and incremental cost-effectiveness ratios were calculated to assess the efficiency of individual statin and combination therapies in reducing LDL-C levels.

Results

The effectiveness in terms of percentage reduction in LDL-C ranged from 19% for pravastatin 10mg/day to 55% for atorvastatin 80mg/day. Annual treatment costs ranged from €189.7 for simvastatin 10mg/day to €759.3 for atorvastatin 80mg/day. The cost-effectiveness ratios, in terms of cost per percentage point reduction in LDL-C, were: €6 for simvastatin, €10–12 for rosuvastatin, €10 for lovastatin, €13–16 for atorvastatin, €13–14 for fluvastatin, and €14–20 for pravastatin. Rosuvastatin + ezetimibe, simvastatin + ezetimibe, and atorvastatin + ezetimibe were the most cost-effective combination therapies for reducing LDL-C levels. Rosuvastatin was the most cost-effective statin for achieving the LDL-C therapeutic goal in patients at high risk for CHD, with a mean cost per patient of €516. Simvastatin was the most cost-effective statin to achieve the LDL-C goal in patients with moderate or low CHD risk, with a cost per patient of €217 and €190, respectively.

Conclusion

Rosuvastatin should be the first-choice agent in patients with high CHD risk, while simvastatin should be the first choice in patients with moderate or low risk. The addition of ezetimibe to rosuvastatin, simvastatin, or atorvastatin should be the preferred combination therapies when greater LDL-C reductions are required. The cost effectiveness of all statin therapies has increased in Spain after the introduction of generic statins and reference prices.     

A pharmacoeconomic evaluation of statins in the treatment of hypercholesterolaemia in the primary care setting in Spain

BACKGROUND: Cardiovascular disease is one of the leading causes of death and it has been shown that primary prevention with the HMG-CoA reductase inhibitor (statin) lipid-lowering drugs can reduce cardiovascular events. Acquisition costs vary between statins and this may be an important consideration in the overall cost effectiveness (CE) of different options. OBJECTIVE: To perform a CE study of the main statins used in Spain for primary prevention of cardiovascular disease in patients with high cholesterol levels [corrected] STUDY DESIGN: The CE analysis was based on an open-label, prospective, naturalistic, randomised intervention study under usual care conditions in primary care settings in patients with high cholesterol levels (total cholesterol [TC] >240 mg/dL, low-density lipoprotein cholesterol [LDL-C] >160 mg/dL) and one or more cardiovascular risk factors. The analysis was conducted from the perspective of the Spanish National Health System; the year of costing was 2001. PATIENTS: A total of 161 patients (49.7% males), mean age 65 +/- 10.3 years, without evidence of cardiovascular disease were included in the study. Of those, 82.1% were hypertensive, 37.1% had diabetes mellitus and 17.9% were smokers. INTERVENTIONS: Forty-eight patients received oral atorvastatin 10 mg/day, 32 received fluvastatin 40 mg/day, 44 received simvastatin 20 mg/day and 37 patients received pravastatin 20 mg/day for 6 months. MAIN MEASUREMENTS AND RESULTS: After 6 months, the therapeutic goals of LDL-C control, according to the recommendations of the Spanish Society of Arteriosclerosis--Consensus-2000, were reached in 62.5%, 43.8%, 45.5% and 40.5% of patients treated with atorvastatin, fluvastatin, simvastatin and pravastatin, respectively. The average CE ratio, expressed as the cost in euros (euro) per patient achieving the therapeutic goals, was euros 424.3 for atorvastatin, euros 503.5 for fluvastatin, euros 527.0 for simvastatin and euros 683.4 for pravastatin. The incremental CE ratios for atorvastatin versus fluvastatin and simvastatin were euros 238.9 and euros 149.5, respectively, per additional patient reaching therapeutic goals. Atorvastatin, fluvastatin and simvastatin all dominated pravastatin. CONCLUSIONS: All the statins studied have been shown to be effective for reducing both TC and LDL-C levels. In this study, atorvastatin was the most efficient drug, with the best CE ratio (cost per patient reaching therapeutic goals). Atorvastatin was more effective and less costly than pravastatin, and when compared with fluvastatin or simvastatin the additional cost per additional patient achieving therapeutic goals was 相似文献   

Dose-dependent influence of two-week administration of simvastatin and metoprolol injection on the blood pressure in normocholesterolemic rats

Beta-blockers are widely used in clinical practice. It is connected with their multiple cardiac effects: slowing heart rate, decrease of myocardial contractility and lowering of systemic blood pressure. Early use of beta-blocker in acute myocardial infarction reduces the risks of reinfarction and ventricular fibrillation. However, the above effects may be associated with the risk of cardiogenic shock. Many patients with cardiovascular diseases receiving beta-blockers are recommended to statin therapy, as well. There are several reports indicating that statins have beneficial cardiovascular effects through their broad spectrum of cholesterol-independent action. It has been revealed that statins could decrease blood pressure, as well. The aim of the study was to evaluate the influence of simvastatin in different doses and metoprolol injection on the blood pressure in normocholesterolemic rats. The experiments were performed on Wistar rats, outbred males. Simvastatin at 1, 10 and 20 mg/kg or vehicle (0.2% methylcellulose) were given intragastrically during two-week period. After two week simvastatin administration, rats were injected intraperitoneally with metoprolol at 5 mg/kg b. w. The arterial blood pressure signals were provided by Isotec pressure transducer connected to a direct current bridge amplifier and catheter was implanted into the right carotid artery. CONCLUSION: Two week administration of simvastatin in different doses to normocholesterolaemic rats does not modify metoprolol impact on the blood pressure.     

基于层次分析法合理选择他汀类药物

目的基于最高的性价比选择他汀类药物。方法在调脂强度达标的范围内,基于层次分析法构建评价指标体系,确定减低LDL-C强度和价格为评价指标,设计问卷调查表确定个体化的评价指标权重,使用matlab软件进行矩阵计算,根据结果选择最适合患者长期治疗的性价比最高的他汀类药物。结果根据患者调脂目标及经济能力合理选择他汀,如更关注药物的调脂强度,则依次选择阿托伐他汀40mg,瑞舒伐他汀10mg,阿托伐他汀20mg,辛伐他汀20mg,阿托伐他汀10mg,辛伐他汀40mg,氟伐他汀80mg,普伐他汀80mg及普伐他汀40mg。如更加关注价格,依次选择辛伐他汀20mg,阿托伐他汀10mg,氟伐他汀80mg,辛伐他汀40mg,瑞舒伐他汀10mg,阿托伐他汀20mg,普伐他汀40mg,阿托伐他汀40mg及普伐他汀80mg。如药物的调脂强度和价格同等重要,则依次选择辛伐他汀20mg,阿托伐他汀10mg,氟伐他汀80mg,辛伐他汀40mg,瑞舒伐他汀10mg,阿托伐他汀20mg,阿托伐他汀40mg,普伐他汀40mg及普伐他汀80mg。结论在调脂强度达标的范围内,可以通过层次分析法获得最适合患者的性价比最高的他汀类药物。     

Hypocholesterolemic effects of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors in the guinea pig: atorvastatin versus simvastatin.

Male Hartley guinea pigs were fed a hypercholesterolemic diet rich in lauric and myristic acids with 0, 10, or 20 mg/kg of simvastatin or atorvastatin for 21 days. Atorvastatin and simvastatin resulted in a lowering of plasma low-density lipoprotein (LDL) cholesterol in a dose-dependent manner by an average of 48 and 61% with 10 and 20 mg/kg, respectively. Both statins were equally effective in lowering plasma LDL cholesterol and apolipoprotein B (apo-B) levels. Atorvastatin and simvastatin treatments yielded LDL particles that differed in composition from the control. Due to the relevance of LDL oxidation and cholesteryl ester transfer in plasma to the progression of atherosclerosis, these parameters were analyzed after statin treatment. Atorvastatin and simvastatin treatment decreased the susceptibility of LDL particles to oxidation by 95% as determined by the formation of thiobarbituric acid reactive substances. An 80% decrease in the transfer of cholesteryl ester between high-density lipoprotein (HDL) and the apo-B-containing lipoproteins was observed after simvastatin and atorvastatin treatment. In addition, statin effects on plasma LDL transport were studied. Simvastatin- and atorvastatin-treated guinea pigs exhibited 125 and 175% faster LDL fractional catabolic rates, respectively, compared with control animals. No change in LDL apo-B flux was induced by either treatment; however, LDL apo-B pool size was reduced after statin treatment. Hepatic microsomal free cholesterol was lower in the atorvastatin and simvastatin groups. However, only atorvastatin treatment resulted in an 80% decrease of acyl-CoA:cholesterol acyltransferase activity (P < 0.001). In summary, atorvastatin and simvastatin had similar LDL cholesterol lowering properties, but these drugs modified LDL transport and hepatic cholesterol metabolism differently.     

Implementation of a therapeutic-interchange clinic for HMG-CoA reductase inhibitors.

A therapeutic-interchange clinic for statins is described. In 1999, the Department of Defense mandated the use of cerivastatin and simvastatin as the formulary statins in all military health care facilities by April 2000. Cerivastatin was the preferred agent; the goal was to use this agent in 60-65% of all patients. Walter Reed Army Medical Center developed a voluntary therapeutic-interchange clinic for patients receiving statins. Goals included facilitating the rapid switching of patients to the formulary statins, maximizing the use of the preferred agent, maintaining or improving lipid control, monitoring safety, determining costs, educating patients about their treatment, and documenting satisfaction with the clinic. Written educational materials were prepared, an algorithm for statin conversion was created, and laboratory tests were performed, among other measures. Between January and April 2000, 1356 patients were seen by the therapeutic-interchange clinic; of these, 942 agreed to have the efficacy and safety of their therapy monitored by the clinic. Before the formulary change, the most commonly prescribed statins were atorvastatin (44% of patients) and pravastatin (42%). Under the conversion policy, 96% of patients received cerivastatin and 4% simvastatin. The percentage of patients achieving their targeted low-density-lipoprotein cholesterol concentration increased from 65% to 75%. The policy saved an average of $115 per patient in the first year. Most patients were satisfied with the clinic, but only 36% of providers were satisfied. Cerivastatin was withdrawn from the market in August 2001; simvastatin became the only formulary statin. A therapeutic-interchange clinic at a military medical center provided an efficient means of switching a large number of patients to alternative statin therapy, monitoring the outcomes, and individualizing patient care.