Shviro I, Leitersdorf E
Center for Research, Prevention and Treatment of Atherosclerosis, Hadassah University Hospital, Jerusalem, Israel.
Br J Clin Pract Suppl. 1996 Jan;77A:24-7.
Both the European Atherosclerosis Society and the US National Cholesterol Education Program have issued revised guidelines for the prevention of coronary heart disease (CHD), based on a multitude of recent epidemiological and angiographic studies. Both authorities agree that a target plasma low-density lipoprotein cholesterol (LDL-C) level is the single most important parameter, this target level being different for primary and secondary prevention. The introduction of statins for the treatment of hypercholesterolaemia provides an important tool to enable target LDL-C levels to be reached in most cases of primary prevention. For secondary prevention, however, the target LDL-C levels--2.6 mmol/l (100 mg/dl)--may be achieved in only a fraction of cases. Others may require the concomitant administration of other cholesterol-lowering drugs, such as bile-acid sequestrants (resins) and/or derivatives of fibric acid (fibrates). The use of statin-fibrate combinations has been discouraged since the report by the US Food and Drug Administration of 12 sporadic cases of myositis or rhabdomyolysis. During the past 7 years, however, 21 clinical trials have examined the efficacy and safety of statin-fibrate combinations in a total of 486 patients with a variety of dyslipidaemias. Overall, the combinations were proven to be effective and safe, and the incidence of abnormalities in liver function tests and levels of creatine kinase (CK) was low. A double-blind study has been carried out at the Hadassah University Hospital to examine the efficacy and safety of fluvastatin when combined with either cholestyramine (group 1) or bezafibrate (group 2) for the treatment of 38 patients with heterozygous familial hypercholesterolaemia (FH). Patients in group 2 showed a reduction in plasma LDL-C levels of 35% and in LDL-C to high-density lipoprotein cholesterol (HDL-C) ratio of 45% compared with 32% and 38% respectively in group 1. Both cholestyramine and bezafibrate produced an additional benefit of a 13% reduction in LDL-C levels in comparison with fluvastatin as monotherapy. An open-label ongoing study on a larger cohort of FH patients reveals that a decrease in plasma LDL-C levels of up to 38.5% may be achieved with a combination of fluvastatin 80 mg/day and bezafibrate 400 mg/day. In both studies, biochemical safety analyses revealed no notable abnormalities in liver function tests or levels of CK. It was concluded that fluvastatin-bezafibrate is a very effective synergistic therapy for heterozygous FH and is superior to a fluvastatin-cholestyramine combination.
欧洲动脉粥样硬化学会和美国国家胆固醇教育计划均已根据近期大量的流行病学和血管造影研究结果，发布了预防冠心病（CHD）的修订指南。双方均认为，血浆低密度脂蛋白胆固醇（LDL-C）目标水平是唯一最重要的参数，该目标水平在一级预防和二级预防中有所不同。他汀类药物用于治疗高胆固醇血症，为在大多数一级预防病例中达到LDL-C目标水平提供了重要工具。然而，对于二级预防，仅部分病例可实现LDL-C目标水平——2.6 mmol/l（100 mg/dl）。其他病例可能需要联合使用其他降胆固醇药物，如胆汁酸螯合剂（树脂）和/或纤维酸衍生物（贝特类药物）。自美国食品药品监督管理局报告12例散发性肌炎或横纹肌溶解病例后，不鼓励使用他汀类药物与贝特类药物的联合疗法。然而，在过去7年中，21项临床试验对他汀类药物与贝特类药物联合使用在总共486例各种血脂异常患者中的疗效和安全性进行了研究。总体而言，联合疗法被证明是有效且安全的，肝功能检查异常和肌酸激酶（CK）水平异常的发生率较低。哈达萨大学医院开展了一项双盲研究，以检验氟伐他汀分别与考来烯胺（第1组）或苯扎贝特（第2组）联合使用治疗38例杂合子家族性高胆固醇血症（FH）患者的疗效和安全性。第2组患者的血浆LDL-C水平降低了35%，LDL-C与高密度脂蛋白胆固醇（HDL-C）的比值降低了45%，而第1组分别为32%和38%。与单独使用氟伐他汀相比，考来烯胺和苯扎贝特均使LDL-C水平额外降低了13%。一项针对更大队列FH患者的开放标签正在进行的研究表明，氟伐他汀80 mg/天与苯扎贝特400 mg/天联合使用可使血浆LDL-C水平降低高达38.5%。在两项研究中，生化安全性分析均显示肝功能检查或CK水平无明显异常。得出的结论是，氟伐他汀-苯扎贝特是治疗杂合子FH的一种非常有效的协同疗法，优于氟伐他汀-考来烯胺联合疗法。
