Key result
Resmetirom cuts LDL-C by ~19% vs. placebo in MASH, regardless of baseline statin use.
Why the study?
Cardiovascular morbidity and mortality are high in metabolic dysfunction-associated steatohepatitis, and the effects of resmetirom on atherogenic lipids and lipoproteins by baseline statin use were evaluated.
Does resmetirom improve MASH outcomes and reduce atherogenic lipids in patients with noncirrhotic MASH consistently irrespective of baseline statin use?
RCT
Does resmetirom improve MASH outcomes and reduce atherogenic lipids in patients with noncirrhotic MASH consistently irrespective of baseline statin use?
Resmetirom demonstrates consistent improvements in MASH endpoints and significant reductions in atherogenic lipids and lipoproteins (LDL-C, ApoB, Lp(a)) irrespective of baseline statin therapy, without increasing statin-related adverse events.
Background Cardiovascular morbidity and mortality are high in metabolic dysfunction-associated steatohepatitis (MASH, previously 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. 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. 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. Conclusions Consistently within the baseline statin subgroups, treatment with resmetirom improved multiple MASH endpoints and LDL-C, ApoB, and Lp(a) profiles.
No takes yet. Share an insight, caveat, or question.
Bansal et al. (2026) conducted an RCT in Metabolic dysfunction-associated steatohepatitis (MASH). Resmetirom vs. Placebo was evaluated on Placebo-corrected percentage change in LDL-C at 24 weeks with 100 mg resmetirom in patients on statin therapy (-18.7%). In patients with MASH, resmetirom improved MASH endpoints and reduced atherogenic lipids irrespective of baseline statin use, including an 18.7% placebo-corrected LDL-C reduction with 100 mg.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: