Mata Pedro, Alonso Rodrigo, Badimón Juan
Lipid Clinic, Internal Medicine Department, Fundación Jiménez Díaz, Madrid, Spain.
Drug Saf. 2003;26(11):769-86. doi: 10.2165/00002018-200326110-00003.
Familial hypercholesterolaemia is a frequent, inherited, monogenic disorder, associated with accelerated development of atherosclerotic disease leading to coronary artery disease. Life expectancy of patients with familial hypercholesterolaemia is reduced by 15-30 years unless they are adequately treated with lipid-lowering therapy. Given the chronic nature of this disease, the selection of a therapeutic approach should be strongly based on its long-term safety and tolerability. The introduction of HMG-CoA reductase inhibitors has revolutionised the treatment of familial hypercholesterolaemia. Simvastatin 40-80 mg/day effectively reduces serum low density lipoprotein (LDL)-cholesterol levels. Furthermore, simvastatin reduces triglycerides and mildly raises high density lipoprotein-cholesterol levels. In addition to the hypolipidaemic effect, other potentially important effects, such as improvement of endothelial function and reduction of LDL oxidation and vascular inflammation, have been associated with HMG-CoA reductase inhibitor therapy. Simvastatin has also been shown to abolish the progression, and even facilitate the regression, of existing human atherosclerotic lesions. The good safety and tolerability profile of simvastatin is clearly highlighted by the low rate of therapy discontinuation observed in several population-based clinical trials. The most common adverse events leading to the discontinuation of therapy are gastrointestinal upset and headache. Asymptomatic elevations in liver transaminase levels and myopathy are uncommon. The overwhelming clinical evidence regarding the long-term use of HMG-CoA reductase inhibitor therapy in patients with familial hypercholesterolaemia together with the long-term safety data (particularly relating to simvastatin) provide support for the use of this drug as a first-line agent when pharmacological treatment is indicated. Early intervention with simvastatin treatment can be successfully implemented with favourable economic benefits.
家族性高胆固醇血症是一种常见的遗传性单基因疾病，与动脉粥样硬化疾病的加速发展相关，可导致冠状动脉疾病。除非接受充分的降脂治疗，家族性高胆固醇血症患者的预期寿命会缩短15至30年。鉴于这种疾病的慢性性质，治疗方法的选择应强烈基于其长期安全性和耐受性。HMG-CoA还原酶抑制剂的引入彻底改变了家族性高胆固醇血症的治疗。辛伐他汀40-80毫克/天可有效降低血清低密度脂蛋白（LDL）胆固醇水平。此外，辛伐他汀可降低甘油三酯并轻度升高高密度脂蛋白胆固醇水平。除了降脂作用外，HMG-CoA还原酶抑制剂治疗还具有其他潜在的重要作用，如改善内皮功能、减少LDL氧化和血管炎症。辛伐他汀还被证明可消除现有人类动脉粥样硬化病变的进展，甚至促进其消退。在几项基于人群的临床试验中观察到的低治疗中断率清楚地突出了辛伐他汀良好的安全性和耐受性。导致治疗中断的最常见不良事件是胃肠道不适和头痛。无症状的肝转氨酶水平升高和肌病并不常见。关于家族性高胆固醇血症患者长期使用HMG-CoA还原酶抑制剂治疗的压倒性临床证据以及长期安全性数据（特别是与辛伐他汀相关的数据）为在需要药物治疗时将该药物用作一线药物提供了支持。早期使用辛伐他汀治疗可以成功实施，并具有良好的经济效益。
