MAESTRO-NASH: Resmetirom May Reduce Cardiovascular Risk in MASH, With or Without Statins

Resmetirom (rezdiffra) may reduce cardiovascular (CV) risk in patients with metabolic dysfunction-associated steatohepatitis (MASH) by significantly improving multiple atherogenic lipids and lipoproteins, including LDL-C, ApoB, and Lp(a), regardless of baseline statin use.

The data come from a secondary analysis of phase 3 MAESTRO-NASH, which was presented at the European Association for the Study of the Liver (EASL) Congress 2026, highlighting resmetirom's potential to target liver disease and cardiometabolic risk in MASH.

"While we see that improvement in fibrosis and MASH resolution, when you can also have that cardiovascular benefit, you know, you're in that one-stop shopping, right?" abstract presenter Meena Bansal, MD, professor of medicine and system chief of the Division of Liver Diseases at the Icahn School of Medicine at Mount Sinai told HCPLive in a post-conference interview. "You're improving everything, and you're really having a holistic view of the patient."

An estimated 5.3% of adults worldwide are living with MASH, and the natural history demonstrates that as liver fibrosis progresses, the incidence of both liver events, including progression to cirrhosis and hepatocellular carcinoma (HCC), and extrahepatic events such as cardiovascular complications and non-liver cancer increases. Cardiovascular disease is the leading cause of death in these patients.

About Resmetirom

Resmetirom is a once-daily, oral, liver-directed thyroid hormone receptor (THR)-β agonist designed to address key underlying causes of MASH by actively increasing the hepatic uptake of LDL-C and helping convert cholesterol into bile acids for excretion. By specifically targeting THR-β in the liver, resmetirom accelerates lipid metabolism without causing the unwanted systemic or cardiac side effects generally associated with thyroid hormones.

Resmetirom became the first therapeutic approved by the US Food and Drug Administration (FDA) for MASH in March 2024.

MAESTRO-NASH Design and Key Findings

In MAESTRO-NASH, 966 adults with biopsy-confirmed MASH, fibrosis stages F1 to F3, a NAFLD Activity Score (NAS) ≥ 4, were randomized to receive 80 mg, 100 mg, or a placebo once a day.

At 52 weeks, resmetirom demonstrated a significant advantage over placebo in 2 co-primary endpoints, including improvement of fibrosis by 1 ≥ stage without worsening of MASH (24.2% for 80 mg and 25.9% for 100 mg vs. 14.2% for placebo) and resolution of MASH without worsening of fibrosis (25.9% on 80 mg and 29.9% on 100 mg vs. 9.7% on placebo, all with P < .001). Resmetirom also resulted in significant decreases in liver fat fraction (35.4% and 46.6% vs. 8.7% for the placebo) and LDL cholesterol levels (−13.6% and −16.3% vs. 0.1%, P < .001). Participants also had better liver biochemistry and markers of disease progression.

"The beauty of the study is that half the people were on a statin, and whether or not you were on a statin, you got additional benefits, so even if you were on a statin, you had further reduction in these, like LDL — now statins don't typically impact Lp(a), which makes this even more exciting, because as data is emerging, it really seems as though Lp(a) is an important predictor of cardiovascular risk, and now is becoming more routinely checked."

Editor’s Note: Bansal reports relevant disclosures with Boeheringer-Ingelheim, Boston Pharma, Fibronostics, GSK, Madrigal, Merck, NOVO Nordisk, and others.

References

1. Madrigal to Present New Data from the Company’s MASH Program at EASL 2026 Demonstrating the Effects of Rezdiffra on Markers of Cardiovascular and Portal Hypertension Risk | Madrigal Pharmaceuticals, Inc. Madrigal Pharmaceuticals, Inc. Published 2026. Accessed June 10, 2026. https://ir.madrigalpharma.com/news-releases/news-release-details/madrigal-present-new-data-companys-mash-program-easl-2026

2. Tiwari A, Sharma A, Kumar H, et al. Resmetirom for MASH: A Comprehensive Review of a Novel Therapeutic Frontier. PubMed. Published August 26, 2025. Accessed June 10, 2026. https://pmc.ncbi.nlm.nih.gov/articles/PMC12467964/