Division of Endocrinology and Metabolism, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, USA.
N Engl J Med. 2010 Mar 11;362(10):906-16. doi: 10.1056/NEJMoa0905633.
Dyslipidemia increases the risk of atherosclerotic cardiovascular disease and is incompletely reversed by statin therapy alone in many patients. Thyroid hormone lowers levels of serum low-density lipoprotein (LDL) cholesterol and has other potentially favorable actions on lipoprotein metabolism. Consequently, thyromimetic drugs hold promise as lipid-lowering agents if adverse effects can be avoided.
We performed a randomized, placebo-controlled, double-blind, multicenter trial to assess the safety and efficacy of the thyromimetic compound eprotirome (KB2115) in lowering the level of serum LDL cholesterol in patients with hypercholesterolemia who were already receiving simvastatin or atorvastatin. In addition to statin treatment, patients received either eprotirome (at a dose of 25, 50, or 100 microg per day) or placebo. Secondary outcomes were changes in levels of serum apolipoprotein B, triglycerides, and Lp(a) lipoprotein. Patients were monitored for potential adverse thyromimetic effects on the heart, bone, and pituitary.
The addition of placebo or eprotirome at a dose of 25, 50, or 100 microg daily to statin treatment for 12 weeks reduced the mean level of serum LDL cholesterol from 141 mg per deciliter (3.6 mmol per liter) to 127, 113, 99, and 94 mg per deciliter (3.3, 2.9, 2.6, and 2.4 mmol per liter), respectively, (mean reduction from baseline, 7%, 22%, 28%, and 32%). Similar reductions were seen in levels of serum apolipoprotein B, triglycerides, and Lp(a) lipoprotein. Eprotirome therapy was not associated with adverse effects on the heart or bone. No change in levels of serum thyrotropin or triiodothyronine was detected, although the thyroxine level decreased in patients receiving eprotirome.
In this 12-week trial, the thyroid hormone analogue eprotirome was associated with decreases in levels of atherogenic lipoproteins in patients receiving treatment with statins. (ClinicalTrials.gov number, NCT00593047.)
血脂异常会增加动脉粥样硬化性心血管疾病的风险，并且在许多患者中，仅用他汀类药物治疗并不能完全逆转。甲状腺激素可降低血清低密度脂蛋白（LDL）胆固醇水平，并对脂蛋白代谢产生其他潜在有利作用。因此，如果能避免不良反应，拟甲状腺药物有望成为降脂药物。
我们进行了一项随机、安慰剂对照、双盲、多中心试验，以评估甲状腺模拟化合物 eprotirome（KB2115）在降低接受辛伐他汀或阿托伐他汀治疗的高胆固醇血症患者血清 LDL 胆固醇水平方面的安全性和疗效。除了他汀类药物治疗外，患者还接受了 eprotirome（剂量为 25、50 或 100μg/天）或安慰剂治疗。次要结局是血清载脂蛋白 B、甘油三酯和 Lp(a)脂蛋白水平的变化。监测患者潜在的甲状腺模拟药物对心脏、骨骼和垂体的不良影响。
在他汀类药物治疗的基础上加用安慰剂或 25、50 或 100μg/天的 eprotirome 治疗 12 周，可使血清 LDL 胆固醇水平从 141mg/dL（3.6mmol/L）降至 127、113、99 和 94mg/dL（3.3、2.9、2.6 和 2.4mmol/L），平均降低幅度分别为 7%、22%、28%和 32%（与基线相比的平均降低值）。血清载脂蛋白 B、甘油三酯和 Lp(a)脂蛋白水平也有类似的降低。eprotirome 治疗与心脏或骨骼的不良反应无关。尽管接受 eprotirome 治疗的患者甲状腺素水平下降，但未检测到血清促甲状腺激素或三碘甲状腺原氨酸水平的变化。
在这项为期 12 周的试验中，甲状腺激素类似物 eprotirome 可降低接受他汀类药物治疗的患者的致动脉粥样硬化脂蛋白水平。（临床试验.gov 编号，NCT00593047。）
