Hamilton-Craig Ian, Kostner Karam, Colquhoun David, Woodhouse Stan
Griffith University School of Medicine, Southport, Queensland, Australia.
Vasc Health Risk Manag. 2010 Nov 10;6:1023-37. doi: 10.2147/VHRM.S13496.
High-dose potent statin therapy in combination with ezetimibe is now standard practice for the treatment of adult patients with heterozygous familial hypercholesterolemia (heFH), as the result of numerous studies in patients with primary hypercholesterolemia or heFH. These studies have shown the combination to be both effective and safe in the short to medium term. Recently, short-term ezetimibe therapy has also been shown to be effective and safe in combination with statin therapy for children and adolescents with heFH. Effective statin-ezetimibe combination therapy is capable of achieving near-normal lipid profiles in heFH patients, with expected improvement in risk for cardiovascular disease (CVD) and improved life expectancy resulting predominantly from reduction in levels of low-density lipoprotein cholesterol. There are few data to support a pleiotropic action of ezetimibe with regard to CVD benefit, unlike therapy with statins. No serious and unexpected clinical adverse effects of combination statin-ezetimibe therapy have emerged till date, although data are limited in children and adolescents, for whom longer-term studies are required. Recent data suggesting possible proatherogenic effects of ezetimibe require confirmation. One large long-term randomized controlled clinical outcomes trial is in progress in non-FH patients to determine the efficacy and safety of ezetimibe therapy; it is unlikely that such a trial will ever be performed in patients with FH.
鉴于在原发性高胆固醇血症或杂合子家族性高胆固醇血症（heFH）患者中开展了大量研究，高剂量强效他汀类药物联合依折麦布治疗现已成为治疗成年heFH患者的标准疗法。这些研究表明，该联合疗法在短期至中期内既有效又安全。最近，短期依折麦布治疗联合他汀类药物治疗heFH儿童和青少年也显示出有效且安全。有效的他汀类药物 - 依折麦布联合疗法能够使heFH患者的血脂水平接近正常，心血管疾病（CVD）风险有望改善，预期寿命延长，这主要是由于低密度脂蛋白胆固醇水平降低所致。与他汀类药物治疗不同，几乎没有数据支持依折麦布在CVD获益方面具有多效性作用。尽管儿童和青少年的数据有限，尚需进行长期研究，但迄今为止，他汀类药物 - 依折麦布联合治疗尚未出现严重且意外的临床不良反应。最近有数据表明依折麦布可能具有促动脉粥样硬化作用，这需要进一步证实。一项针对非FH患者的大型长期随机对照临床结局试验正在进行中，以确定依折麦布治疗的疗效和安全性；在FH患者中进行这样的试验不太可能。
