What future for combination therapies?

John Kastelein
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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.

联合疗法的未来如何?
对于大多数需要降脂治疗的患者,他汀类药物单药治疗是合适的治疗方法。然而,在那些他汀类药物单一治疗不能产生最佳脂质水平的患者中,他汀类药物与烟酸、胆汁酸隔离剂、纤维酸衍生物、胆固醇吸收抑制剂或鱼油制剂联合使用可能会改善控制。联合治疗的选择取决于患者的血脂和药物的耐受性。对于低密度脂蛋白胆固醇(LDL-C)水平非常高的患者,应考虑将他汀类药物与烟酸、胆汁酸隔离剂或依折替米贝(一种胆固醇吸收抑制剂)联合使用,而对于LDL-C和甘油三酯水平较高的患者,应考虑将他汀类药物与纤维酸衍生物或鱼油联合使用。许多新的降脂药物目前正在开发中,包括胆固醇酯转移蛋白(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、微粒体甘油三酯转移蛋白(MTP)抑制剂和双过氧化物酶体增殖激活受体(PPAR) α和γ激动剂。这些新疗法的引入将为开发不同的联合策略提供机会,这些策略可能有助于优化目前难以治疗的患者的脂质谱。新组合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到最低。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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