Univ. Lille Nord de France, Lille, France.
Curr Opin Lipidol. 2009 Dec;20(6):505-11. doi: 10.1097/MOL.0b013e328332e9ef.
Despite the fact that statin treatment substantially reduces cardiovascular morbidity and mortality, many treated patients still experience a high residual risk. Statins lower LDL cholesterol (LDL-C), with limited effects on other lipid parameters. Fibrates improve atherogenic dyslipidemia characterized by high triglyceride and/or low HDL cholesterol levels and elevated concentrations of small dense LDL particles, with or without high LDL-C levels. Fibrates decrease cardiovascular morbidity, especially in patients with the metabolic syndrome. The purpose of this review is to provide a rationale for the combined use of statins and fibrates in the management of patients with high residual cardiovascular risk related to atherogenic dyslipidemia and persisting after single therapy.
A meta-analysis from 14 randomized trials conducted in high-risk patients reported that statin therapy is effective in reducing the proportional risk for major vascular events by 21% for each mmol/l lowering of LDL-C. However, on an average, 14% of patients still experienced an event despite being allocated to statin. Beyond LDL-C, other factors, including triglycerides, non-HDL cholesterol, HDL cholesterol, and apolipoprotein B, have been identified as factors determining residual risk, and normalization of these parameters may further decrease cardiovascular disease in patients treated with statins. Data from fibrate trials indicate that these drugs are particularly effective in reducing cardiovascular morbidity in patients with atherogenic dyslipidemia.
Reducing the residual cardiovascular risk in patients treated with statins requires addressing multiple lipid goals. In this context, future therapeutic interventions based on combination therapy, such as statins and fibrates, appear particularly promising.
综述目的：尽管他汀类药物治疗可显著降低心血管发病率和死亡率，但许多接受治疗的患者仍存在较高的残余风险。他汀类药物可降低 LDL 胆固醇（LDL-C），但对其他脂质参数的影响有限。贝特类药物可改善致动脉粥样硬化性血脂异常，其特征为甘油三酯和/或 HDL 胆固醇水平低、小而密 LDL 颗粒浓度升高，且无论 LDL-C 水平高低。贝特类药物可降低心血管发病率，尤其是在代谢综合征患者中。本文旨在为他汀类药物和贝特类药物联合用于治疗致动脉粥样硬化性血脂异常相关的高残余心血管风险患者提供依据，这些患者在单药治疗后仍存在残余风险。
最新发现：一项纳入 14 项高危患者随机试验的荟萃分析报告称，他汀类药物治疗可使 LDL-C 每降低 1mmol/L，主要血管事件的比例风险降低 21%。然而，平均而言，尽管将患者分配到他汀类药物治疗组，仍有 14%的患者发生了事件。除 LDL-C 外，其他因素，包括甘油三酯、非 HDL 胆固醇、HDL 胆固醇和载脂蛋白 B，已被确定为决定残余风险的因素，而这些参数的正常化可能会进一步降低接受他汀类药物治疗的患者的心血管疾病风险。贝特类药物试验数据表明，这些药物在降低致动脉粥样硬化性血脂异常患者的心血管发病率方面特别有效。
总结：降低接受他汀类药物治疗患者的残余心血管风险需要满足多个脂质目标。在这种情况下，基于联合治疗（如他汀类药物和贝特类药物）的未来治疗干预措施似乎特别有前景。
