所有的他汀类药物都一样吗?关注匹伐他汀的疗效和耐受性。
Are all statins the same? Focus on the efficacy and tolerability of pitavastatin.
机构信息
Núcleo de Investigação Arterial, Medicina IV - Hospital de Sta. Marta, CHLC, EPE, Lisbon, Portugal.
出版信息
Am J Cardiovasc Drugs. 2011;11(2):93-107. doi: 10.2165/11591190-000000000-00000.
Pitavastatin is the newest member of the HMG-CoA reductase inhibitor family and is approved as adjunctive therapy to diet to reduce elevated levels of total cholesterol, low-density lipoprotein (LDL) cholesterol, apolipoprotein (Apo) B, and triglycerides and to increase levels of high-density lipoprotein (HDL) cholesterol in adult patients with primary hyperlipidemia or mixed dyslipidemia. Pitavastatin undergoes minimal metabolism by cytochrome P450 (CYP) enzymes and, therefore, has a low propensity for drug-drug interactions with drugs metabolized by CYP enzymes or the CYP3A4 substrate grapefruit juice. In clinical trials, pitavastatin potently and consistently reduced serum levels of total, LDL, and non-HDL cholesterol, and triglycerides in patients with primary hypercholesterolemia where diet and other non-pharmacological measures were inadequate. Mean reductions from baseline in serum total and LDL cholesterol and triglyceride levels were 21-32%, 30-45%, and 10-30%, respectively. Moreover, a consistent trend towards increased HDL cholesterol levels of 3-10% was seen. Long-term extension studies show that the beneficial effects of pitavastatin are maintained for up to 2 years. Pitavastatin produces reductions from baseline in serum total and LDL cholesterol levels to a similar extent to those seen with the potent agent atorvastatin and to a greater extent than those seen with simvastatin or pravastatin. In the majority of other studies comparing pitavastatin and atorvastatin, no significant differences in the favorable effects on lipid parameters were seen, although pitavastatin was consistently associated with trends towards increased HDL cholesterol levels. Pitavastatin also produces beneficial effects on lipids in patients with type 2 diabetes mellitus and metabolic syndrome without deleterious effects on markers of glucose metabolism, such as fasting blood glucose levels or proportion of glycosylated hemoglobin. Pitavastatin appears to exert a number of beneficial effects on patients at risk of cardiovascular events independent of lipid lowering. In the JAPAN-ACS (Japan Assessment of Pitavastatin and Atorvastatin in Acute Coronary Syndrome) study, pitavastatin was non-inferior to atorvastatin at reducing plaque volume in patients with ACS undergoing percutaneous coronary intervention. Further beneficial effects, including favorable effects on the size and composition of atherosclerotic plaques, improvements in cardiovascular function, and improvements in markers of inflammation, oxidative stress, and renal function, have been demonstrated in a number of small studies. Pitavastatin is generally well tolerated in hyperlipidemic patients with or without type 2 diabetes, with the most common treatment-related adverse events being musculoskeletal or gastrointestinal in nature. Increases in plasma creatine kinase levels were seen in <5% of pitavastatin recipients and the incidence of myopathy or rhabdomyolysis was extremely low. In summary, pitavastatin, the latest addition to the statin family, produces potent and consistent beneficial effects on lipids, is well tolerated, and has a favorable pharmacokinetic profile. The combination of a potent decrease in total and LDL cholesterol levels and increase in HDL cholesterol levels suggest that pitavastatin may produce substantial cardiovascular protection.
匹伐他汀是 HMG-CoA 还原酶抑制剂家族的最新成员,被批准作为饮食辅助疗法,用于降低原发性高脂血症或混合性血脂异常成年患者的总胆固醇、低密度脂蛋白(LDL)胆固醇、载脂蛋白(Apo)B 和甘油三酯水平,并升高高密度脂蛋白(HDL)胆固醇水平。匹伐他汀几乎不通过细胞色素 P450(CYP)酶代谢,因此与 CYP 酶代谢的药物或 CYP3A4 底物葡萄柚汁发生药物相互作用的可能性很低。在临床试验中,匹伐他汀在饮食和其他非药物措施不足的原发性高胆固醇血症患者中,强有力且一致地降低了血清总胆固醇、LDL 胆固醇和非高密度脂蛋白胆固醇及甘油三酯水平。血清总胆固醇和 LDL 胆固醇及甘油三酯水平从基线的平均降低幅度分别为 21-32%、30-45%和 10-30%。此外,还观察到 HDL 胆固醇水平持续升高 3-10%的一致趋势。长期扩展研究表明,匹伐他汀的有益作用可维持长达 2 年。匹伐他汀与强效药物阿托伐他汀相比,使血清总胆固醇和 LDL 胆固醇水平降低的幅度相似,与辛伐他汀或普伐他汀相比幅度更大。在比较匹伐他汀和阿托伐他汀的大多数其他研究中,虽然匹伐他汀与 HDL 胆固醇水平升高趋势相关,但未见对脂质参数有显著的有利影响。匹伐他汀对 2 型糖尿病和代谢综合征患者的血脂也有有益作用,且对葡萄糖代谢标志物(如空腹血糖水平或糖化血红蛋白比例)无不良影响。匹伐他汀似乎对心血管事件风险患者有许多有益作用,而不仅仅是降低血脂。在 JAPAN-ACS(日本评估匹伐他汀和阿托伐他汀在急性冠状动脉综合征中的应用)研究中,在接受经皮冠状动脉介入治疗的急性冠状动脉综合征患者中,匹伐他汀在降低斑块体积方面不劣于阿托伐他汀。在一些小型研究中还证明了其他有益作用,包括对动脉粥样硬化斑块大小和组成的有利影响、改善心血管功能以及改善炎症、氧化应激和肾功能标志物。匹伐他汀在伴有或不伴有 2 型糖尿病的高脂血症患者中通常耐受性良好,最常见的与治疗相关的不良事件为肌肉骨骼或胃肠道性质。接受匹伐他汀治疗的患者中不到 5%出现血浆肌酸激酶水平升高,肌病或横纹肌溶解症的发生率极低。总之,匹伐他汀是他汀类药物家族的最新成员,对血脂有强有力且一致的有益作用,耐受性良好,具有良好的药代动力学特征。总胆固醇和 LDL 胆固醇水平的显著降低以及 HDL 胆固醇水平的升高提示匹伐他汀可能产生实质性的心血管保护作用。