Manhas Amit, Farmer John A
Section of Cardiology, Baylor College of Medicine, One Baylor Plaza, MS 523D, Houston, TX 77030, USA.
Curr Atheroscler Rep. 2004 Mar;6(2):89-93. doi: 10.1007/s11883-004-0095-5.
The advent of safe and effective hypolipidemic therapy has revolutionized the ability of the clinician to optimize abnormalities in the lipid profile. The advent of statin therapy has provided a potent option to decrease low-density lipoprotein and frequently allows achievement of National Cholesterol Education Program target lipid levels with monotherapy. However, lipid goals are frequently not achieved due to inadequate response to therapy or side effects. The role of combination therapy in the optimization of the lipid profile provides a means by which the implementation of pharmacologic agents with synergistic mechanisms of action allows further improvement in circulating levels of low-density lipoprotein cholesterol. Statins have been combined with bile acid resins, fibric acid derivatives, and nicotinic acid. However, bile acid resins, although not systemically absorbed, have significant problems with patient compliance and drug interactions. The implementation of therapy with fibric acid derivatives or nicotinic acid increases the risk of significant side effects such as rhabdomyolysis or liver toxicity. Ezetimibe is a prototype of a new class of agents that specifically block the absorption of cholesterol from the gastrointestinal tract. Ezetimibe has minimal systemic absorption and a metabolic pathway involving enterohepatic circulation that allows for once a day administration due to a prolonged half-life. Ezetimibe lacks the drug interactions that are common with the bile acid resins and it may be utilized as either monotherapy or in combination with other pharmacologic agents. Ezetimibe has a relatively flat dose-response curve and titration is not required. This review centers on the role of pharmacologic agents that act predominantly by the reduction of cholesterol absorption, including colesevelam and ezetimibe.
安全有效的降血脂疗法的出现，彻底改变了临床医生优化血脂异常的能力。他汀类药物疗法的出现，为降低低密度脂蛋白提供了一种有效选择，且常能通过单一疗法实现国家胆固醇教育计划设定的血脂目标水平。然而，由于对治疗反应不足或出现副作用，血脂目标常常无法实现。联合疗法在优化血脂谱方面的作用，提供了一种手段，即通过使用具有协同作用机制的药物，进一步降低循环中的低密度脂蛋白胆固醇水平。他汀类药物已与胆汁酸螯合剂、纤维酸衍生物和烟酸联合使用。然而，胆汁酸螯合剂尽管不会被全身吸收，但在患者依从性和药物相互作用方面存在重大问题。使用纤维酸衍生物或烟酸进行治疗会增加出现严重副作用的风险，如横纹肌溶解或肝毒性。依泽替米贝是一类新型药物的代表，这类药物能特异性地阻断胃肠道对胆固醇的吸收。依泽替米贝全身吸收极少，其代谢途径涉及肠肝循环，由于半衰期较长，因而可以每日服用一次。依泽替米贝没有胆汁酸螯合剂常见的药物相互作用，它既可以作为单一疗法使用，也可以与其他药物联合使用。依泽替米贝的剂量反应曲线相对平缓，无需滴定。本综述聚焦于主要通过减少胆固醇吸收起作用的药物的作用，包括考来维仑和依泽替米贝。
