Journal of Clinical Lipidology · Oct 15, 2026

Potential for cardiovascular benefits of resmetirom based on LDL-cholesterol and lipoprotein(a) lowering consistent across statin subgroups, a secondary analysis of the MAESTRO-NASH phase 3 clinical trial

By Bansal MB, Taub R, Labriola D et al.

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.

doi.org/10.1016/j.jacl.2026.10.004Open accessPubMed 42995030Interventions