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联合疗法的未来何去何从?

What future for combination therapies?

作者信息

Kastelein John

机构信息

Academic Medical Center, Amsterdam, The Netherlands.

出版信息

Int J Clin Pract Suppl. 2003 Mar(134):45-50.

Abstract

For most patients who require lipid-lowering treatment, statin monotherapy is the appropriate treatment. However, in those patients where statin monotherapy does not produce optimal lipid levels, the combination of a statin with niacin, a bile acid sequestrant, a fibric acid derivative, a cholesterol absorption inhibitor or a fish oil preparation may provide improved control. The choice of combination therapy depends upon the patient's lipid profile and tolerability of the medication. Combination of a statin with niacin, a bile acid sequestrant or ezetimibe, a cholesterol absorption inhibitor, should be considered for patients with very high low-density lipoprotein cholesterol (LDL-C) levels, while combination with either a fibric acid derivative or a fish oil should be considered for patients with high LDL-C and high triglyceride levels. A number of new lipid-lowering agents are currently in development, including cholesteryl ester transfer protein (CETP) inhibitors, acyl coenzyme A: cholesterol acyltransferase (ACAT) inhibitors, ileal bile acid transport (IBAT) inhibitors, microsomal triglyceride transfer protein (MTP) inhibitors and dual peroxisome proliferator-activated receptor (PPAR) alpha and gamma agonists. Introduction of these novel therapies will provide opportunities for developing different combination strategies that may help to optimise lipid profiles in patients who are currently difficult to treat. The introduction of new combinations will require careful study to ensure that the risks of drug interactions and adverse events are minimised.

摘要

对于大多数需要降脂治疗的患者,他汀类单药治疗是合适的治疗方法。然而,在那些他汀类单药治疗不能使血脂水平达到最佳的患者中,他汀类与烟酸、胆汁酸螯合剂、贝特类衍生物、胆固醇吸收抑制剂或鱼油制剂联合使用可能会更好地控制血脂。联合治疗方案的选择取决于患者的血脂情况和药物耐受性。对于低密度脂蛋白胆固醇(LDL-C)水平极高的患者,应考虑他汀类与烟酸、胆汁酸螯合剂或胆固醇吸收抑制剂依泽替米贝联合使用;对于LDL-C和甘油三酯水平均高的患者,则应考虑与贝特类衍生物或鱼油联合使用。目前有多种新型降脂药物正在研发中,包括胆固醇酯转运蛋白(CETP)抑制剂、酰基辅酶A:胆固醇酰基转移酶(ACAT)抑制剂、回肠胆汁酸转运(IBAT)抑制剂、微粒体甘油三酯转运蛋白(MTP)抑制剂以及过氧化物酶体增殖物激活受体(PPAR)α和γ双重激动剂。这些新型疗法的引入将为制定不同的联合治疗策略提供机会,有助于优化目前难以治疗的患者的血脂情况。新联合治疗方案的引入需要仔细研究,以确保药物相互作用和不良事件的风险降至最低。

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