Chapman M John
Institut National de la Santé et de la Recherche Mé dicale, Hôpital de la Pitié, Paris, France.
Cardiovasc Drugs Ther. 2005 Mar;19(2):135-9. doi: 10.1007/s10557-005-1049-z.
Reduction of low-density lipoprotein cholesterol (LDL-C) with statin therapy is currently identified in treatment guidelines as the primary focus for patients with or at risk of coronary heart disease (CHD). Yet despite effective statin therapy there is still an unacceptably high residual coronary risk. A substantial proportion of patients with CHD have mixed dyslipidemia, including low levels of high-density lipoprotein cholesterol (HDL-C), an independent and predictive risk factor for CHD. Although effective in reducing LDL-C, statin therapy has only modest effects in raising HDL-C. Fibrate therapy is an alternative lipid-modifying strategy, and is effective in reducing CHD mortality and morbidity, with the magnitude of clinical benefit similar to statin therapy. Multi-drug therapy with complementary mechanisms of action has been proposed as a means of improving lipid-modifying efficacy. Nicotinic acid is the most potent agent for increasing HDL-C and also substantially reduces LDL-C and triglycerides. Addition of nicotinic acid to statin therapy would be a logical management approach, given the potential for complementary therapeutic benefit. The clinical benefits of this combination are supported by the results of the HDL Atherosclerosis Treatment Study, which showed reduction of 60-90% in the incidence of major coronary events when both agents were administered. In addition, combination treatment led to angiographic regression of stenosis, compared with placebo, rather than slowed progression as previously reported with statin monotherapy. Given that the prevalence of low HDL-C, particularly amongst individuals with CHD, is higher than previously anticipated, combining nicotinic acid and a statin represents an innovative approach to further reducing CHD risk.
目前，治疗指南将他汀类药物治疗降低低密度脂蛋白胆固醇（LDL-C）作为冠心病（CHD）患者或有冠心病风险患者的主要治疗重点。然而，尽管他汀类药物治疗有效，但仍存在高得令人无法接受的残余冠心病风险。相当一部分冠心病患者存在混合性血脂异常，包括高密度脂蛋白胆固醇（HDL-C）水平低，这是冠心病的一个独立且具有预测性的风险因素。他汀类药物治疗虽然能有效降低LDL-C，但在升高HDL-C方面效果有限。贝特类药物治疗是另一种脂质调节策略，可有效降低冠心病死亡率和发病率，临床获益程度与他汀类药物治疗相似。已提出采用具有互补作用机制的多药联合治疗来提高脂质调节疗效。烟酸是升高HDL-C最有效的药物，还能大幅降低LDL-C和甘油三酯。鉴于可能带来互补性治疗益处，在他汀类药物治疗中添加烟酸将是一种合理的治疗方法。HDL动脉粥样硬化治疗研究的结果支持了这种联合治疗的临床益处，该研究表明，同时使用这两种药物时，主要冠状动脉事件的发生率降低了60 - 90%。此外，与安慰剂相比，联合治疗导致血管造影显示的狭窄程度有所减轻，而不像之前报道的他汀类单药治疗那样只是减缓进展。鉴于低HDL-C的患病率，尤其是在冠心病患者中，高于之前的预期，联合使用烟酸和他汀类药物是进一步降低冠心病风险的一种创新方法。
