Stein Evan A
Metabolic and Atherosclerosis Research Center and Medical Research Laboratories International, Cincinnati, Ohio 45229, USA.
Am Heart J. 2002 Dec;144(6 Suppl):S43-50. doi: 10.1067/mhj.2002.130302.
Lipid-lowering agents have been shown to reduce morbidity and mortality associated with coronary heart disease (CHD), particularly in high-risk patients. The identification and treatment of these patients should therefore be a high priority for clinicians. Guidelines from medical organizations, such as the National Cholesterol Education Program Adult Treatment Panel (NCEP ATP) and the American Diabetes Association (ADA), suggest that patients with low-density lipoprotein cholesterol (LDL-C) levels > or =130 mg/dL, and perhaps even those with levels > or =100 mg/dL, should receive drug therapy. Optimal LDL-C levels have been set at <100 mg/dL and <115 mg/dL for high-risk patients by US and European guidelines, respectively. However, a recent survey shows that only about 20% of high-risk patients currently meet these goals. In order to achieve therapeutic targets for LDL-C, the statins are the foundation of treatment, as they are the most effective and best-tolerated form of lipid-lowering therapy. Other therapeutic options include bile acid sequestrants, niacin, and plant stanols, although seldom as monotherapy. Combination therapy with a statin and one of these other lipid-lowering agents can be useful in patients who are unable to achieve target lipid levels through monotherapy. There remains, however, a need for additional agents. Some of the new options for reducing LDL-C levels that may be available in the near future include 2 new statins, pitavastatin and rosuvastatin. In patients with heterozygous familial hypercholesterolemia, rosuvastatin, which is currently under review by the Food and Drug Administration (FDA), has been shown to produce significantly greater reductions in LDL-C than atorvastatin over its full dose range. In comparative clinical trials, it has also enabled more patients with primary hypercholesterolemia to meet lipid goals than atorvastatin, simvastatin, and pravastatin. Inhibitors of bile acid transport or cholesterol absorption may also have therapeutic value. The first cholesterol absorption inhibitor, ezetimibe, which has just been approved by the FDA, appears to be most effective when combined with a statin. It is anticipated that such new options will allow clinicians to optimize the management of dyslipidemia in high-risk patients, thereby reducing the morbidity and mortality of CHD.
降脂药物已被证明可降低与冠心病(CHD)相关的发病率和死亡率,尤其是在高危患者中。因此,识别和治疗这些患者应是临床医生的首要任务。诸如美国国家胆固醇教育计划成人治疗小组(NCEP ATP)和美国糖尿病协会(ADA)等医学组织的指南建议,低密度脂蛋白胆固醇(LDL-C)水平≥130mg/dL的患者,甚至LDL-C水平≥100mg/dL的患者,都应接受药物治疗。美国和欧洲的指南分别将高危患者的最佳LDL-C水平设定为<100mg/dL和<115mg/dL。然而,最近的一项调查显示,目前只有约20%的高危患者达到了这些目标。为了实现LDL-C的治疗目标,他汀类药物是治疗的基础,因为它们是最有效且耐受性最好的降脂治疗形式。其他治疗选择包括胆汁酸螯合剂、烟酸和植物甾醇,不过很少作为单一疗法使用。对于那些通过单一疗法无法达到目标血脂水平的患者,他汀类药物与其他降脂药物之一的联合治疗可能会有用。然而,仍然需要其他药物。一些可能在不久的将来可用的降低LDL-C水平的新选择包括两种新的他汀类药物——匹伐他汀和瑞舒伐他汀。在杂合子家族性高胆固醇血症患者中,目前正在接受美国食品药品监督管理局(FDA)审查的瑞舒伐他汀,在其整个剂量范围内已被证明比阿托伐他汀能更显著地降低LDL-C水平。在比较临床试验中,与阿托伐他汀、辛伐他汀和普伐他汀相比,它还能使更多原发性高胆固醇血症患者达到血脂目标。胆汁酸转运抑制剂或胆固醇吸收抑制剂也可能具有治疗价值。第一种胆固醇吸收抑制剂依泽替米贝刚刚获得FDA批准,与他汀类药物联合使用时似乎最有效。预计这些新选择将使临床医生能够优化高危患者血脂异常的管理,从而降低冠心病的发病率和死亡率。