基于低密度脂蛋白胆固醇和脂蛋白(a)降低的resmetirom心血管获益潜力在他汀类药物各亚组中保持一致，这是MAESTRO-NASH 3期临床试验的一项二次分析。
完整摘要 · 中文译文
背景：代谢功能障碍相关脂肪性肝炎（MASH，既往称非酒精性脂肪性肝炎[NASH]）患者的心血管发病率和死亡率较高。Resmetirom是一种选择性甲状腺激素受体-β激动剂，已获批用于治疗伴中重度肝纤维化的非肝硬化MASH患者。Resmetirom可降低致动脉粥样硬化性脂质和脂蛋白。 目的：本项3期MAESTRO-NASH临床试验的二次分析评估了resmetirom治疗52周对MASH疗效参数、致动脉粥样硬化性脂质、脂蛋白的影响，以及根据基线他汀使用情况的安全性。 方法：分析MAESTRO-NASH试验的数据。分析评估了按基线他汀使用情况分层的MASH和脂质对治疗的反应及安全性，包括连续肝酶测量和不良事件。 结果：基线时，49%的MAESTRO-NASH参与者接受他汀治疗。疗效终点，包括MASH缓解、纤维化改善和肝脏脂肪减少，无论是否使用他汀均可达成。低密度脂蛋白胆固醇（LDL-C）、载脂蛋白B（ApoB）和脂蛋白(a)[Lp(a)]的降低与基线他汀使用情况无关；resmetirom 80 mg和100 mg联合他汀或单药治疗24周时安慰剂校正的百分比变化分别为：LDL-C（-12.0、-18.7[使用他汀]；-15.3、-14.1[未使用他汀]）、ApoB（-16.4、-20.7；-17.9；-19.7）和Lp(a)（-31.2、-26.4；-36.3、-32.8）。在接受100 mg resmetirom的他汀使用患者中，第52周LDL-C <70 mg/dL的人数增加了45.4%，且n 脂蛋白(a)（Lp(a)）<75 nmol/L或<125 nmol/L的人数分别增加36.4%和38.9%。未观察到与statin相关的显著不良事件。所有置信区间或隐含P值均为名义值，未针对多重性进行校正。 结论：在基线statin亚组中，resmetirom治疗一致地改善了多个MASH终点以及LDL-C、ApoB和Lp(a)谱。
完整摘要 · 英文原文
BACKGROUND: Cardiovascular morbidity and mortality are high in metabolic dysfunction-associated steatohepatitis (MASH, previously nonalcoholic steatohepatitis [NASH]). Resmetirom, a selective thyroid hormone receptor-ß agonist, is approved for treatment of patients with noncirrhotic MASH with moderate to advanced liver fibrosis. Resmetirom reduces atherogenic lipids and lipoproteins. OBJECTIVE: This secondary analysis of the phase 3 MAESTRO-NASH clinical trial evaluated effects of resmetirom over 52 weeks on MASH efficacy parameters, atherogenic lipids, lipoproteins, and safety according to baseline statin use. METHODS: Data from the MAESTRO-NASH trial were analyzed. Analyses assessed MASH and lipid responses to treatment and safety, including serial liver enzyme measurements and adverse events by baseline statin use. RESULTS: At baseline, 49% of MAESTRO-NASH participants were on statin therapy. Efficacy endpoints, including MASH resolution, fibrosis improvement, and liver fat reduction, were achieved regardless of statin use. Low-density lipoprotein cholesterol (LDL-C), apolipoprotein B (ApoB), and lipoprotein(a) [Lp(a)] were reduced irrespective of baseline statin use; the placebo-corrected percentage changes at 24 weeks with resmetirom 80 mg and 100 mg, respectively, in combination with statins or alone were: LDL-C (-12.0, -18.7 [on statin]; -15.3, -14.1 [not on statin]), ApoB (-16.4, -20.7; -17.9; -19.7), and Lp(a) (-31.2, -26.4; -36.3, -32.8). In patients on statins who received 100 mg resmetirom, the number with LDL-C <70 mg/dL at week 52 increased by 45.4%, and the number with Lp(a) <75 nmol/L or <125 nmol/L increased by 36.4% and 38.9%, respectively. No significant statin-related adverse events were observed. All confidence intervals or implied P values are nominal and uncorrected for multiplicity. CONCLUSION: Consistently within the baseline statin subgroups, treatment with resmetirom improved multiple MASH endpoints and LDL-C, ApoB, and Lp(a) profiles.