他汀类药物的经济学研究

目的 通过对降血脂药物经济学分析,为临床选择他汀类药物提供帮助。方法 对国产和进口品种的降脂药物疗效进行了总结,通过分析药物的成本-效果,制定选药方案。结果 辛伐他汀在所有他汀类药物中性价比最高,其次为瑞舒伐他汀钙,然后为普伐他汀钠片,最差的为阿托伐他汀。但辛伐他汀达标时使用剂量偏大,造成不良反应较多,目前大多研究不支持辛伐他汀的降脂疗效。与进口药物相比,国产药价格优势明显。结论 与其他他汀类药物相比,瑞舒伐他汀降脂疗效明确,价格相对较低,不良反应少,建议首选瑞舒伐他汀钙降脂。     

生物样品中他汀类降脂药检测方法的研究进展

他汀类药物是临床上常用的一类降脂药,包括洛伐他汀、普伐他汀、辛伐他汀、氟伐他汀、阿托伐他汀和瑞舒伐他汀。这类药物降脂作用强,抗动脉粥样硬化作用肯定,耐受性好。现综述生物样品中此类降脂药的色谱检测法,并介绍作者实验室使用的简单灵敏的色谱检测方法。这些新方法能促进他汀类药物的药动学研究和低剂量给药药物浓度监测的发展,对于药物的进一步开发和临床用药浓度监测有非常重要的作用。     

他汀类药物的不良反应分析

目的：分析他汀类药物临床应用不良反应发生情况及特点。方法：收集我院2015年2月～2016年2月使用他汀类药物33例出现不良反应病例资料,对患者一般情况、用药情况及不良反应表现进行统计分析。结果：33例不良反应共涉及辛伐他汀、阿托伐他汀和瑞舒伐他汀3种用药,症状表现以消化系统反应和泌尿系统反应为主。结论：规范他汀类药物临床用药,严格控制使用剂量,注意适用范围及与其他药物配伍,可有效减少不良反应。     

瑞舒伐他汀与氟伐他汀治疗不稳定型心绞痛临床观察

目的对比瑞舒伐他汀与氟伐他汀治疗不稳定型心绞痛的疗效。方法选取在我院心内科住院的不稳定型心绞痛患者180例,随机分为两组,瑞舒伐他汀组:在常规治疗(抗血小板药物、抗凝血药物、硝酸酯类药物、钙离子拮抗剂等)基础上给予瑞舒伐他汀10mg,每晚1次,共用药8周;氟伐他汀组:在常规治疗(抗血小板药物、抗凝血药物、硝酸酯类药物、钙离子拮抗剂等)基础上给予氟伐他汀40 mg,每晚1次,共用药8周,分别测定治疗前后两组患者血中的LDL-C、HDL-C和CRP水平及患者心绞痛症状变化情况。结果瑞舒伐他汀组和氟伐他汀组治疗前比较各项指标差异无统计学意义(P>0.05)。瑞舒伐他汀组和氟伐他汀组治疗后疗效和各项指标比较均有统计学意义(P<0.05)。结论瑞舒伐他汀和氟伐他汀都能够改善不稳定型心绞痛患者的心绞痛症状,但是瑞舒伐他汀治疗不稳定型心绞痛患者的效果明显优于氟伐他汀。     

1例瑞舒伐他汀联用缬沙坦致梗阻性黄疸的药学监护

目的 探讨临床药师参与的1例冠心病患者联用瑞舒伐他汀和缬沙坦引起肝损害所致的梗阻性黄疸的药学监护。方法 介绍临床药师参与1例冠心病患者的治疗过程,从药理学角度分析他汀类药物引起的肝损害与剂量、代谢及其他药物相互作用的关系,并提供相关建议。结果 医师只考虑由他汀类药物引起,而临床药师利用专业知识,提出瑞舒伐他汀钙与缬沙坦胶囊的相互作用最大,建议同时停用缬沙坦胶囊。结论 通过医师与药师的合作,从而促进合理用药,保证患者用药的安全有效。同时,也为临床药师实施药学监护提供一种新的思维方式。     

阿托伐他汀联合胺碘酮致肝药酶升高2例分析

目的:提示临床重视阿托伐他汀联合胺碘酮致肝药酶升高的不良反应。方法:报道并分析我院心内科2例心肌梗死患者予阿托伐他汀联合胺碘酮后出现肝药酶升高的病例。结果与结论:未见文献报道阿托伐他汀联合胺碘酮致肝药酶升高的病例。他汀类药物与其他药物仍然存在相互作用的危险,临床应慎重或避免合用,在用药过程中仔细观察患者的异常表现,定期复查肝肾功能,发现问题及时处理,避免严重不良反应发生。     

2011～2012年某院降脂药物用药分析

目的:分析本院2011 ～ 2012年降脂类药物的使用情况,为临床合理用药提供依据.方法:采用限定日剂量(DDD)分析法,对我院2011 ～ 2012年降脂药物的销售金额和用药频度进行统计、综合分析.结果:2012年间降脂药物用药金额年增长率为46.27,用药频度不断升高.他汀类药物为我院主要使用的降脂药物,其中阿托伐他汀的用药金额和用药频度两年均排在首位,阿托伐他汀和瑞舒伐他汀是用药频度增长速度最快的药物.结论:两年来我院降脂药物应用稳定,使用合理,他汀类药物在我院降脂药物使用中占主导地位.     

上海地区119家医院2010-2012年调脂药利用分析

目的:了解上海地区医院调脂药的应用情况及趋势。方法:采用回顾性方法,对上海地区119家医院2010-2012年调脂药的品种、销售金额、用药频度(DDDs)、日均费用(DDC)等进行统计、分析。结果:各年度调脂药的总销售金额逐年增长,且增速逐年扩大;他汀类药物占调脂药市场的绝对主导地位,其后依次为中成药类和贝特类;2010-2011年销售金额排序列前3位的是阿托伐他汀、辛伐他汀和普伐他汀,2012年依次为阿托伐他汀、瑞舒伐他汀和辛伐他汀;2010-2011年DDDs排序列前3位的是阿托伐他汀、辛伐他汀和非诺贝特,2012年依次为阿托伐他汀、辛伐他汀和瑞舒伐他汀。结论:高效、安全、依从性好的他汀类药物成为调脂药中的优先选择药物,今后市场前景继续看好。     

瑞舒伐他汀钙致肝功能损害不良反应分析

目的：分析瑞舒伐他汀钙致不良反应（ADR）的一般规律与特点,为ADR监测及临床合理用药提供参考。方法：对无锡市人民医院上报的瑞舒伐他汀钙所致肝损害ADR 9例进行分析。结果：在瑞舒伐他汀钙引起的ADR中,女性2例,男性7例,所发生的ADR均为肝酶升高、肝功能异常,其中有1例同时发生横纹肌溶解。结论：临床上应加强对瑞舒伐他汀钙应用的监测,特别是用药期间肝、肾功能及肌酸激酶（CK）的监测,正确进行用药安全评估,以减少ADR的发生。     

北京地区多家医院2009-2012年调脂药利用分析

目的：了解北京地区医院调脂药的应用情况及变化趋势。方法：采用回顾性方法,对北京地区多家医院2009-2012年调脂药的应用品种、销售金额、用药频度、日均费用等指标进行统计、分析。结果：北京地区医院调脂药销售金额、用药频度逐年升高;最常用的是他汀类药物,其销售金额占调脂药总销售金额的约80％;用量最大的品种主要是阿托伐他汀、瑞舒伐他汀、辛伐他汀、阿昔莫司、普伐他汀。结论：他汀类调脂药是临床治疗高脂血症的一线药物,占市场主导地位,前景看好。     

Rosuvastatin: a high-potency HMG-CoA reductase inhibitor.

OBJECTIVE: To summarize the relevant pharmacologic, clinical, and safety data regarding rosuvastatin (Crestor--AstraZeneca), the most recently marketed 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor approved for the treatment of dyslipidemia. DATA SOURCES: Medline search from years 1990 thru 2005 using the keywords HMG-CoA reductase inhibitor, hypercholesterolemia, lipid-lowering agents, rosuvastatin, and statins. Study Selection: Review articles, clinical trials, case reports, abstracts, and data on file from the manufacturer concerning rosuvastatin and other statins were considered for inclusion. DATA EXTRACTION: English-language studies were selected for inclusion. DATA SYNTHESIS: Multiple clinical trials have revealed that use of rosuvastatin is associated with greater reductions in low-density lipoprotein cholesterol (LDL-C) across the dose range of 5-40 mg/day than any other currently available statins. Rosuvastatin also significantly increases high-density lipoprotein cholesterol and reduces triglycerides significantly as well. In clinical trials, rosuvastatin was well tolerated, with a low incidence of adverse events and a safety profile similar to that of the other marketed statins. At present, no large-scale primary or secondary prevention clinical trials document either long-term safety of rosuvastatin or its effectiveness in preventing coronary events. CONCLUSION: Compared with other statins, rosuvastatin offers the greatest lipid-lowering efficacy at the lowest dose in treating patients with dyslipidemia and with a similar safety profile over the short-term. Rosuvastatin may allow more patients to achieve their LDL-C goals than any other statin and at a lower dose than other agents.     

Achieving 2003 European lipid goals with rosuvastatin and comparator statins in 6743 patients in real-life clinical practice: DISCOVERY meta-analysis

BACKGROUND: There is an increasing body of evidence to support the benefits of reducing low-density lipoprotein cholesterol (LDL-C) levels and this has been reflected in a lowering of LDL-C goals recommended by international guidelines. Therefore, there is a growing need for effective lipid-modifying therapies to optimise the achievement of these more stringent LDL-C goals. OBJECTIVE: A meta-analysis of data pooled from five studies participating in the DISCOVERY (DIrect Statin COmparison of LDL-C Values: an Evaluation of Rosuvastatin therapY) Programme was performed to compare the effect of rosuvastatin treatment with other statins in real-life clinical practice. RESULTS: These studies included 6743 patients with hypercholesterolaemia from different ethnicities, countries and cultural environments. The meta-analysis showed that significantly more patients receiving rosuvastatin 10 mg achieved the 2003 European LDL-C goals compared with those who received atorvastatin 10 mg or simvastatin 20 mg (p < 0.001 for both comparisons). A significantly greater proportion of patients receiving rosuvastatin 10 mg also achieved the 2003 European total cholesterol goal compared with those on atorvastatin 10 mg (p < 0.001). CONCLUSIONS: The meta-analysis showed that rosuvastatin was more effective than comparator statins at lowering LDL-C levels and enabling patients to achieve lipid goals at recommended start doses. In addition, all statins studied were well tolerated and confirmed that rosuvastatin had a similar safety profile to other statins.     

Rosuvastatin: new preparation. Opt for statins with evidence of efficacy on clinical outcome

(1) Simvastatin and pravastatin are the two reference statins for type IIA and type IIB hypercholesterolaemia because they have the best-documented protective effect against cardiovascular events. Simvastatin and pravastatin are also the reference statins for familial heterozygous hypercholesterolaemia, though there is no evidence that they prevent cardiovascular events in this group. Statins are not very effective in familial homozygous hypercholesterolaemia. (2) Rosuvastatin is the sixth statin to arrive on the French market. The fifth, cerivastatin, was withdrawn from the market in 2001 because of serious adverse effects. (3) Rosuvastatin has not been assessed in terms of morbidity or mortality. The results of comparative trials in type IIA and type IIB hypercholesterolaemia suggest that rosuvastatin is slightly more active than simvastatin, pravastatin and atorvastatin on some lipid parameters after a few weeks of treatment. (4) Rosuvastatin has not been compared with simvastatin or pravastatin in familial heterozygous hypercholesterolaemia. One trial showed it to be slightly more effective than atorvastatin on cholesterol levels. According to one trial, rosuvastatin does not appear to be more effective than atorvastatin in homozygous forms. (5) In clinical trials the adverse effects of rosuvastatin were similar to those of other statins, with the exception of renal adverse effects. We don't know whether rosuvastatin is more or less likely than other statins to cause rhabdomyolysis. (6) Clinical trials reported some cases of proteinuria and renal failure suggesting there is a need for more thorough assessment in long-term trials. (7) In practice, statins with the best-documented benefits (simvastatin and pravastatin) should be used first for cardiovascular prevention in patients with hypercholesterolaemia.     

Rosuvastatin-Associated Adverse Effects and Drug-Drug Interactions in the Clinical Setting of Dyslipidemia

HMG-CoA reductase inhibitors (statins) are the mainstay in the pharmacologic management of dyslipidemia. Since they are widely prescribed, their safety remains an issue of concern. Rosuvastatin has been proven to be efficacious in improving serum lipid profiles. Recently published data from the JUPITER study confirmed the efficacy of this statin in primary prevention for older patients with multiple risk factors and evidence of inflammation. Rosuvastatin exhibits high hydrophilicity and hepatoselectivity, as well as low systemic bioavailability, while undergoing minimal metabolism via the cytochrome P450 system. Therefore, rosuvastatin has an interesting pharmacokinetic profile that is different from that of other statins. However, it remains to be established whether this may translate into a better safety profile and fewer drug-drug interactions for this statin compared with others. Herein, we review evidence with regard to the safety of this statin as well as its interactions with agents commonly prescribed in the clinical setting. As with other statins, rosuvastatin treatment is associated with relatively low rates of severe myopathy, rhabdomyolysis, and renal failure. Asymptomatic liver enzyme elevations occur with rosuvastatin at a similarly low incidence as with other statins. Rosuvastatin treatment has also been associated with adverse effects related to the gastrointestinal tract and central nervous system, which are also commonly observed with many other drugs. Proteinuria induced by rosuvastatin is likely to be associated with a statin-provoked inhibition of low-molecular-weight protein reabsorption by the renal tubules. Higher doses of rosuvastatin have been associated with cases of renal failure. Also, the co-administration of rosuvastatin with drugs that increase rosuvastatin blood levels may be deleterious for the kidney. Furthermore, rhabdomyolysis, considered a class effect of statins, is known to involve renal damage. Concerns have been raised by findings from the JUPITER study suggesting that rosuvastatin may slightly increase the incidence of physician-reported diabetes mellitus, as well as the levels of glycated hemoglobin in older patients with multiple risk factors and low-grade inflammation. Clinical trials proposed no increase in the incidence of neoplasias with rosuvastatin treatment compared with placebo. Drugs that antagonize organic anion transporter protein 1B1-mediated hepatic uptake of rosuvastatin are more likely to interact with this statin. Clinicians should be cautious when rosuvastatin is co-administered with vitamin K antagonists, cyclosporine (ciclosporin), gemfibrozil, and antiretroviral agents since a potential pharmacokinetic interaction with those drugs may increase the risk of toxicity. On the other hand, rosuvastatin combination treatment with fenofibrate, ezetimibe, omega-3-fatty acids, antifungal azoles, rifampin (rifampicin), or clopidogrel seems to be safe, as there is no evidence to support any pharmacokinetic or pharmacodynamic interaction of rosuvastatin with any of these drugs. Rosuvastatin therefore appears to be relatively safe and well tolerated, sharing the adverse effects that are considered class effects of statins. Practitioners of all medical practices should be alert when rosuvastatin is prescribed concomitantly with agents that may increase the risk of rosuvastatin-associated toxicity.     

The safety of rosuvastatin: effects on renal and hepatic function

Statins, or 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, have been shown to reduce elevated serum cholesterol resulting in a reduced risk of coronary artery disease and its complications. Rosuvastatin is the latest of the class of HMG-CoA reductase inhibitors and has the most potent reduction of low-density lipoprotein and elevation of high-density lipoprotein in the class. Questions have been raised about its safety. In a careful examination of the data, rosuvastatin has the same rate of elevations of hepatic enzymes as the other statins. Whether any of the statins actually cause significant liver injury is doubtful, and this raises questions about the usefulness of routine monitoring of liver enzymes in statin patients. Rosuvastatin has been noted to produce low levels of transient proteinuria. However, transient proteinuria is seen with other comparable statins. Long-term administration of rosuvastatin and other statins have been shown not to be associated with any decline in renal function, but instead have been shown to produce modest but clear improvement in glomerular filtration rate. Therefore, it is clear that rosuvastatin, and other statins, are very safe and useful agents and do not appear to present significant risks to hepatic or renal safety.     

Rosuvastatin: renal disorders and rhabdomyolysis

(1) Rosuvastatin was not evaluated for its impact on morbidity or mortality. In premarketing trials its adverse effects seemed similar to those observed with other statins. In addition, there were questions concerning renal adverse effects, particularly dose-dependent proteinuria. Inadequate information was available to know whether the risk of rhabdomyolysis differed from that of other statins. (2) A review of adverse events reported to the FDA in late 2004 showed that reports of renal and muscular adverse events were more frequent with rosuvastatin than with other statins currently on the market. (3) Regulatory agencies analysed their results and issued warnings, but they withheld the raw data. This is regrettable, especially given the frequent use of the drug, the specific risks associated with this class, and the questions that were left unanswered in its initial clinical evaluation. Healthcare professionals and the public need access to more precise data on rosuvastatin. (4) In practice, it is better to select the two statins with the most thorough clinical assessments, namely simvastatin and pravastatin.     

Achieving 2003 European lipid goals with rosuvastatin and comparator statins in 6743 patients in real-life clinical practice: DISCOVERY meta-analysis

ABSTRACT

Background: There is an increasing body of evidence to support the benefits of reducing low-density lipoprotein cholesterol (LDL-C) levels and this has been reflected in a lowering of LDL-C goals recommended by international guidelines. Therefore, there is a growing need for effective lipid-modifying therapies to optimise the achievement of these more stringent LDL-C goals.

Objective: A meta-analysis of data pooled from five studies participating in the DISCOVERY (DIrect Statin COmparison of LDL‐C Values: an Evaluation of Rosuvastatin therapY) Programme was performed to compare the effect of rosuvastatin treatment with other statins in real-life clinical practice.

Results: These studies included 6743 patients with hypercholesterolaemia from different ethnicities, countries and cultural environments. The meta-analysis showed that significantly more patients receiving rosuvastatin 10?mg achieved the 2003 European LDL‐C goals compared with those who received atorvastatin 10?mg or simvastatin 20?mg (?p < 0.001 for both comparisons). A significantly greater proportion of patients receiving rosuvastatin 10?mg also achieved the 2003 European total cholesterol goal compared with those on atorvastatin 10?mg (?p < 0.001).

Conclusions: The meta-analysis showed that rosuvastatin was more effective than comparator statins at lowering LDL‐C levels and enabling patients to achieve lipid goals at recommended start doses. In addition, all statins studied were well tolerated and confirmed that rosuvastatin had a similar safety profile to other statins.