临床他汀类药物的合理应用分析

目的：探究临床他汀类药物的合理应用情况。方法选取六安市中医院2009年9月—2014年9月收治的36例服用他汀类药物致不良反应的患者资料,分析他汀类药物用药情况、不良反应表现及原因。结果辛伐他汀用药最多,氟伐他汀最少;不良反应发生时间为服药后2.8h~7.4d,以5~12h最多;不良反应多累及消化系统,其次是皮肤、神经肌肉系统、泌尿系统;药物配伍不当、用药剂量或方法不当以及药物自身因素等是不良反应的主要原因,其中用药方法或剂量不当引起的不良反应发生率高于其他因素,差异有统计学意义（ P﹤0.05）。结论在临床治疗过程中应尽量避免将他汀类药物与其他经相同途径代谢的药物配用,应尽量选择已经核实的安全配伍。     

他汀类药物的临床应用

目的：综述他汀类药物应用,为临床选择提供依据。方法：查阅献,结合临床,进行综合分析。结果：他汀类药物具有显降低TC,LDL－c,中度降低TG及轻度升高HDL－c的作用,结论：他汀类药物能逆转脂质异常,减少心血管疾病发生和危险因素,可作为高脂血症或具有冠心病发病高危因素患常规治疗药物。     

他汀类药物与其他药物联用的安全性评价

目的对门诊处方中他汀类药物与其他药物联用的安全性进行评价,以利临床合理用药。方法抽查门诊使用他汀类药物的处方,以药品说明书中的规定为标准,结合近年来公开发表的相关文献,分析他汀类药物与其他药物联用的安全性。结果他汀类药物与其他药物联用基本合理,没有发现联用CYP3A4抑制剂,但有5种CYP3A4底物和地高辛与他汀类药物联用,存在安全隐患。结论他汀类药物与其他药物联用时应注意观察,避免与CYP3A4抑制剂或其底物联用。     

环孢素与他汀类药物在治疗原发性肾病综合征中的相互作用分析

目的：了解该院原发性肾病综合征患者他汀类药物的使用情况,探讨所用的各类他汀类药物与环孢素可能存在的药物相互作用,为临床合理选药提供参考。方法：回顾性分析2022年1—6月该院门诊诊断为原发性肾病综合征患者的他汀类药物使用情况;利用Lexicomp药物相互作用数据库以及药品说明书,对所用他汀类药物的种类及其与环孢素可能存在的药物相互作用进行对比分析。结果：2022年1—6月,该院原发性肾病综合征患者使用的他汀类药物主要包括普伐他汀、氟伐他汀、辛伐他汀、阿托伐他汀和瑞舒伐他汀;其中,药品说明书“禁忌”项中明确列出禁止与环孢素合用的有辛伐他汀和瑞舒伐他汀。在Lexicomp数据库中,与环孢素相互作用为D等级的药物有普伐他汀、氟伐他汀和瑞舒伐他汀;与环孢素相互作用为X等级的药物为辛伐他汀和阿托伐他汀。结论：在原发性肾病综合征的治疗中,环孢素与他汀类药物存在相互作用,文献报道与药品说明书并不完全一致,医师在决策时需综合考量,选择普伐他汀和氟伐他汀可能更理想。     

CYP450介导的他汀类药物相互作用及其药学监护

目的：研究由CYP450介导的他汀类药物相互作用及其药学监护,以期促进他汀类药物的合理使用。方法：通过对近年来的国内外相关文献报道进行收集、归纳、分析,加以综述。结果：多类药物及食物均可通过CYP450与他汀类药物产生相互作用并导致药效降低和（或）不良反应风险增加等后果,需进行有效地药学监护,降低用药风险。结论：使用他汀类药物时,临床药师应从药物的种类和剂量的选择、肝毒性和肌毒性的监测,及患者用药教育等多方面进行药学监护,以确保用药安全。     

他汀类药物与其他药物的相互作用

目的：部分脂溶性他汀药物是CYP3A4／5的底物，其代谢易被其他药物所诱导或抑制，也可能抑制其他药物的代谢，本资料拟总结上述常见的相互作用，供临床用药参考。方法：检索Medline1966—2006年期间公开发表的他汀类与其他药物代谢方面的相互作用文献，进行分析、归纳。结果：他汀类药物与临床经常合用的其他药物包括口服抗凝药、抗感染药物、其他调血脂药物、抗HIB药物等存在临床意义的相互作用。结论：临床对于他汀类药物与其他药物联合应用时应该谨慎，注意避免或减少不良相互作用，保障用药安全有效。     

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。     

3种他汀类药物联合用药处方分析

目的了解他汀类药物的合并用药情况,为临床合理用药提供参考。方法在代谢酶学理论指导下,从代谢性相互作用的角度对处方进行回顾性分析。结果含3种他汀类药物的处方共计2 267张,其中含氟伐他汀和CYP2C9抑制药或底物的处方208张;含阿托伐他汀或辛伐他汀,且有CYP3A4抑制药或底物的处方分别为412和56张。厄贝沙坦、氨氯地平、硝苯地平、那格列奈、泼尼松、非洛地平等出现的频率较高。结论他汀类药物应避免与抑制他汀类药物代谢的药物合用,或选择无或很少相互作用的同类药物。药师在合并用药中应做好处方审查和患者用药教育,必要时对某些可疑相互作用进行血药浓度监测。     

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。     

他汀类药物安全性

他汀类药物通过其有效地降低总胆固醇和LDL胆固醇及药物对动脉粥样硬化的直接作用,在正常和高血脂个体的一、二级预防中,显著降低冠脉突发事件和冠脉性死亡,降低总死亡率.随着这类药物的广泛应用,其安全性越来越受到人们的重视.他汀类药物的毒副作用可能对机体的肝脏功能及骨骼肌、视觉系统、中枢神经系统造成损伤,但通常状态下,这些毒副作用的发生率较低,多为可逆性损害,不会对机体造成很大的损伤,药物的临床效益远远大于其毒副作用的风险.不同类型他汀类药物的毒副作用也不相同.近来,他汀类药物的肌肉毒性及由此引起的肾功能衰竭已经受到人们的重视,有关机制有待于进一步研究.临床上合理、准确地选择药物,严格控制药物剂量、避免药物间相互作用,将有利于控制或减少药物毒副作用的发生.     

他汀类药物肝脏安全性的研究进展及合理选用

随着他汀类药物在临床上的广泛使用,他汀类药物的安全性问题也一直备受关注,最常见的问题是血清转氨酶升高。临床对他汀类药物肝脏安全性的认识不足可能限制他汀类药物的一级和二级预防和治疗应用。本文通过对他汀类药物的说明书、相关指南及文献的查阅和分析,总结了他汀类药物肝脏安全性的研究进展,为临床正确认识他汀类药物肝脏安全性及合理选用提供参考。     

Synthetic statins: more data on newer lipid-lowering agents

Extensive trial evidence supports the use of hydroxy-methyl-glutaryl-CoA reductase inhibitors (HMG-CoA-RI; statins) in atherosclerotic disease. Statins can be divided into two broad groups: the 'natural' statins derived from a fungal metabolites, and synthetic compounds. Whether all statins have similar anti-atherosclerotic properties, or whether these actions are specific to the 'natural' statins, is controversial. This commentary reviews the differences between natural and synthetic statins with regard to lipid-lowering and non-lipid-lowering effects, including their action on the acute phase reactant C-reactive protein. Among the newer synthetic statins, fluvastatin has some positive end-point evidence while cerivastatin shares many biochemical properties with the 'natural' statins. Extensive clinical trial programmes are underway with both atorvastatin and cerivastatin. These trials will give a definitive answer to the question of whether synthetic statins are as equally efficacious as 'natural' statins in preventing atherosclerotic events.     

Synthetic Statins: More Data on Newer Lipid-lowering Agents

SUMMARY

Extensive trial evidence supports the use of hydroxy-methyl-glutaryl-CoA reductase inhibitors (HMG-CoA-RI; statins) in atherosclerotic disease. Statins can be divided into two broad groups: the ‘natural’ statins derived from a fungal metabolites, and synthetic compounds. Whether all statins have similar anti-atherosclerotic properties, or whether these actions are specific to the ‘natural’ statins, is controversial. This commentary reviews the differences between natural and synthetic statins with regard to including their action on the acute phase reactant C-reactive protein. Among the newer synthetic statins, fluvastatin has some positive end-point evidence while cerivastatin shares many biochemical properties with the ‘natural’ statins. Extensive clinical trial programmes are underway with both atorvastatin and cerivastatin. These trials will give a definitive answer to the question of whether synthetic statins are as equally efficacious as ‘natural’ statins in preventing atherosclerotic events.     

HMG-Co A reductase inhibitors in the treatment of cardiovascular diseases: stabilization of coronary artery plaque

3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) are greatly contributed to the treatment of hypercholesterolemia, and constitute an important part of comprehensive strategies for the treatment of cardiovascular disease in the 21st century. Particularly, a strategy for preventing acute coronary syndrome (ACS), the most important complication of hyperlipidemia, is urgently needed. Recent research has revealed a new mechanism of prevention of coronary heart disease by statins: they not only lowered cholesterol level as previously reported, but also contribute directly to plaque stabilization. Among many statins recently marketed, some act directly onto the blood vessel wall to stabilize plaques already formed (so-called vascular statins), while statins are originally classified as chemical or non-chemical. At the same time, reports on pleiotropic activities of statins, including improvement of osteoporosis, have accumulated to suggest an extended role of statins, not merely as a hypolipidemic agent but also possibly an anti-arteriosclerotic/anti-aging drug. This article reviews the direct action of statins on the blood vessel wall, with reference to classification of statins based on difference in action on the blood vessel wall (hepatic statins vs. vascular statins).     

HMG-CoA reductase inhibitors as immunomodulators: potential use in transplant rejection

The benefit of HMG-CoA reductase inhibitors (statins) to the cardiovascular system is now well established and these drugs are being used extensively to treat hypercholesterolaemia clinically. However, as clinical outcomes become available it appears that statins are proving more beneficial than expected and thus it is being proposed that the actions of statins go beyond their ability to lower serum cholesterol levels. The report that statins can interact directly with lymphocyte function-associated antigen (LFA)-1 and prevent it engaging with the intracellular adhesion molecule (ICAM)-1 receptor on T cells is a novel mechanism of statin action and provides convincing evidence that these compounds can regulate biological systems other than by the cholesterol synthesis pathway. Immunosuppression to prevent organ transplant rejection is one application for which statins are currently being assessed. The clinical evidence is conflicting and does not convincingly reflect whether statins are beneficial as immunomodulators. However, in vivo studies investigating the cellular actions of statins have identified two mechanisms by which statins can potentially modulate an in vivo immune response. Firstly, statins regulate inducible class II major histocompatibility complex (MHC) expression on macrophages and endothelial cells. Secondly, statins can inhibit LFA-1 adhesion to ICAM-1 and thus regulate T cell activation. These findings suggest that statins have the potential to regulate an immune response in vivo and that more investigation is essential in order to explain the opposing clinical data.     

Statins and pregnancy: between supposed risks and theoretical benefits

Cardiovascular diseases are the leading cause of mortality in industrialized countries. Treatment with statins is effective in primary prevention in patients at high cardiovascular risk. Statins are inhibitors of hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase and are classed as lipid-lowering drugs. In 2010, atorvastatin was the biggest-selling drug in the world ($US10.73?billion). Increases in the average age of pregnant women and in the prevalence of morbid obesity have inevitably led to exposure to statins in certain women during the first trimester of pregnancy. The teratogenic risk attendant upon use of statins is unclear because the available data are contradictory, but statins remain contraindicated in pregnant women. The benefits of statins in prevention of cardiovascular risk may not be solely due to their cholesterol-lowering effects: the so-called pleiotropic effects of vascular protection lead some experts to posit a potential benefit in the management of preeclampsia. In this review we evaluate the theoretical benefits and supposed risks of statins in pregnant women. After a brief overview of the pharmacodynamic properties of statins, we address the question of the teratogenic risk of statins, and then detail the rationale for the therapeutic potential of statins in preeclampsia.     

Statins as anti-inflammatory agents in atherogenesis: molecular mechanisms and lessons from the recent clinical trials

Ample evidence exists in support of the potent anti-inflammatory properties of statins. In cell studies and animal models statins exert beneficial cardiovascular effects. By inhibiting intracellular isoprenoids formation, statins suppress vascular and myocardial inflammation, favorably modulate vascular and myocardial redox state and improve nitric oxide bioavailability. Randomized clinical trials have demonstrated that further to their lipid lowering effects, statins are useful in the primary and secondary prevention of coronary heart disease (CHD) due to their anti-inflammatory potential. The landmark JUPITER trial suggested that in subjects without CHD, suppression of low-grade inflammation by statins improves clinical outcome. However, recent trials have failed to document any clinical benefit with statins in high risk groups, such in heart failure or chronic kidney disease patients. In this review, we aim to summarize the existing evidence on statins as an anti-inflammatory agent in atherogenesis. We describe the molecular mechanisms responsible for the antiinflammatory effects of statins, as well as clinical data on the non lipid-lowering, anti-inflammatory effects of statins on cardiovascular outcomes. Lastly, the controversy of the recent large randomized clinical trials and the issue of statin withdrawal are also discussed.     

复发性脑梗死患者他汀类药物用药依从性情况调查

目的对复发性脑梗死患者首次发病后使用他汀类药物情况进行调查,探讨引起其临床应用不规范的主要因素。方法从医院2007年9月至2013年12月住院的670例脑梗死患者中筛选出复发性动脉粥样硬化性血栓性脑梗死130例,调查其住院前使用他汀类药物的情况,分析他汀类药物使用不规范的原因。结果 95例（73.08%）患者出院后他汀类药物使用不规范,其中19例（14.62%）虽坚持服用但低密度脂蛋白胆固醇未达标,56例（43.08%）间断服用他汀类药物;20例（15.38%）未服用他汀类药物。他汀类药物使用不规范的主要原因为,患者担心不良反应（如长期服用导致肝功异常）;患者对脑梗死复发认识不足;患者或家属认为无效;患者未坚持内科门诊随访,未接受专科医生指导;门诊医生随访中忽略询问使用情况;患者嫌麻烦;患者因出现副作用而停药。结论相当多的脑梗死患者他汀类药物使用不规范及未能坚持长期服用,调脂达标率较低。应对脑梗死患者加强脑卒中二级预防健康教育,以提高他汀类药物的用药依从性。     

基于FAERS数据库挖掘分析他汀类药物不良反应

目的:利用美国食品药品监督管理局不良事件报告系统开展他汀类药物的不良反应风险分析。方法:采用报告比值比法与贝叶斯置信区间传播神经网络法对他汀类药物的不良反应信号进行分析。结果:新发现他汀类药物部分共性不良反应(大于4种他汀类药物存在的新发不良反应)12种,且他汀类药物糖尿与新发糖尿病之间存在较强的关联性。结论:他汀类药物较为确定的不良反应是血压降低以及新发糖尿病,在骨骼和呼吸系统方面他汀类药物的不良反应与文献报道存在争议,他汀类药物对血液、精神、神经、消化系统、肾脏及泌尿系统方面造成的风险尚未有足够循证医学证据支撑。对他汀类药物的应用后续要持续监测安全性风险,同时要积极合理地使用,提高风险获益水平。