Saely C H, Drexel H, Huber K
Abteilung für Innere Medizin und Kardiologie und VIVIT-Institut, Akademisches Lehrkrankenhaus Feldkirch, Carinagasse 47, 6807, Feldkirch, Österreich.
Herz. 2010 Oct;35(7):497-502. doi: 10.1007/s00059-010-3381-8.
Lowering LDL cholesterol (LDL-C) with statins decreases cardiovascular risk; therefore LDL-C is the primary target in lipid therapy. The amount of risk reduction is the greater, the lower the LDL-C values achieved by statin therapy are. Current guidelines therefore require an LDL-C as low as < 70 mg/dl in patients who are at a very high risk of cardiovascular events. This stringent treatment goal depending on the baseline LDL-C values typically can only be obtained with higher doses of potent statins. Randomised trials demonstrate the efficacy of high-dose therapy with atorvastatin 80 mg/day with regard to the prevention of cardiovascular events in patients after acute coronary syndromes (PROVE-IT TIMI 22 trial), in patients with stable coronary artery disease (TNT trial), and in patients after stroke or TIA (SPARCL trial). Moreover, potent statin treatment reduces the progression of coronary atherosclerosis (REVERSAL and ASTEROID trials). Furthermore, large meta-analyses of the efficacy of high-dose statin therapy confirm its safety; in particular, muscle-related adverse events are not more frequent than with standard statin doses. It is recommended that evidence-based statin doses be used in clinical practice; the dosages used in clinical trials should be given rather than titrating patients to LDL-C targets by increasing statin doses in a stepwise manner. Whether the strong LDL-C lowering combination of simvastatin plus ezetimibe will reduce cardiovascular events over and above simvastatin monotherapy is currently being tested in the ongoing IMPROVE-IT trial. Importantly, despite the large body of evidence in favour of high-dose statin therapy for patients at high cardiovascular risk, high-dose statin therapy is still underused and LDL-C goals are still not met in the majority of these patients.
使用他汀类药物降低低密度脂蛋白胆固醇(LDL-C)可降低心血管风险;因此,LDL-C是血脂治疗的主要目标。他汀类药物治疗所达到的LDL-C值越低,风险降低的幅度就越大。因此,现行指南要求心血管事件极高风险患者的LDL-C低至<70mg/dl。这一严格的治疗目标通常取决于基线LDL-C值,只有使用更高剂量的强效他汀类药物才能实现。随机试验证明,急性冠状动脉综合征患者(PROVE-IT TIMI 22试验)、稳定型冠状动脉疾病患者(TNT试验)以及中风或短暂性脑缺血发作患者(SPARCL试验)使用80mg/日阿托伐他汀高剂量治疗预防心血管事件的疗效。此外,强效他汀类药物治疗可减缓冠状动脉粥样硬化的进展(REVERSAL和ASTEROID试验)。此外,关于高剂量他汀类药物治疗疗效的大型荟萃分析证实了其安全性;特别是,与标准他汀类药物剂量相比,肌肉相关不良事件的发生率并未更高。建议在临床实践中使用基于证据的他汀类药物剂量;应采用临床试验中使用的剂量,而不是通过逐步增加他汀类药物剂量将患者的LDL-C调整至目标值。辛伐他汀加依泽替米贝强效降低LDL-C的联合用药是否能在辛伐他汀单药治疗基础上进一步降低心血管事件,目前正在进行的IMPROVE-IT试验中进行测试。重要的是,尽管有大量证据支持对心血管风险高的患者进行高剂量他汀类药物治疗,但高剂量他汀类药物治疗的使用率仍然较低,这些患者中的大多数仍未达到LDL-C目标。