Resmetirom Cuts CV Risk in MASH: Meena Bansal, MD

Resmetirom improves atherogenic lipid profiles, including low-density lipoprotein cholesterol (LDL-C), apolipoprotein B (ApoB), and lipoprotein(a) (Lp[a]), independent of whether patients with metabolic dysfunction–associated steatohepatitis (MASH) are already on statin therapy, according to a secondary analysis of the phase 3 MAESTRO-NASH trial (NCT03900429) and MAESTRO-NAFLD-1 data (NCT04197479) presented at the European Association for the Study of the Liver Congress.

In an interview with The American Journal of Managed Care^® (AJMC®), Meena Bansal, MD, professor of medicine and system chief of the Division of Liver Diseases at the Icahn School of Medicine at Mount Sinai, discussed what these findings mean for how clinicians should think about resmetirom's cardiovascular (CV) role as a complementary therapy to statins that operates through distinct hepatic mechanisms.

She also addressed the underrecognized burden of elevated Lp(a) in patients with MASH, where atherogenic dyslipidemia and systemic inflammation already compound CV risk, and why routine Lp(a) measurement should become standard practice in hepatology clinics. Bansal made the case for integrated, multidisciplinary care models that bridge hepatology and cardiology and argued that siloed management is no longer adequate for a disease where CV mortality leads all other causes.

AJMC: Cardiovascular disease is a leading cause of mortality in MASH. How can liver-focused specialists and cardiologists work better to care for these patients and improve outcomes?

Bansal: Cardiovascular disease accounts for the largest share of mortality in MASH, yet most patients are managed in silos—seen by hepatologists for liver end points and cardiologists only after an event occurs. Better outcomes require proactive, structured collaboration: routine CV risk scoring in hepatology clinics; standardized referral pathways for patients with elevated ApoB, Lp(a), or subclinical atherosclerosis; and shared treatment targets that account for both liver and cardiovascular disease.

Integrated MASH clinics costaffed by hepatologists, cardiologists, endocrinologists, and dietitians represent the model the field should be moving toward. Trials should also increasingly cocapture liver and CV end points rather than treating them as separate outcomes.

AJMC: Your abstract found that resmetirom improved lipid profiles—LDL-C, ApoB, and Lp(a)—regardless of whether patients were on statins at baseline, and liver efficacy end points held up as well. What does that tell us about resmetirom's role in patients who are already on lipid-lowering therapy?

Bansal: This is an important finding because it positions resmetirom as an additive rather than redundant therapy in patients already on statins. Resmetirom acts selectively on thyroid hormone receptor-β in the liver, driving hepatic LDL receptor upregulation and reducing ApoB-containing lipoprotein secretion through mechanisms largely distinct from statin-mediated HMG-CoA reductase inhibition.

The fact that lipid benefits—including LDL-C, ApoB, and Lp(a) reductions—and liver histology end points were preserved irrespective of background statin therapy suggests the drug operates through a complementary pathway. Resmetirom may provide additional CV benefits that statins do not and needs to be further studied.

AJMC: Lp(a) is often overlooked in liver disease management. Why does it matter so much for patients with MASH specifically, and how should clinicians be thinking about it?

Bansal: Unlike most lipoproteins, Lp(a) promotes both atherosclerosis and thrombosis through its ApoA component, and it is largely resistant to conventional lipid-lowering strategies. In the context of MASH, where atherogenic dyslipidemia, insulin resistance, and systemic inflammation already conspire to elevate CV risk, an elevated Lp(a) represents an additional, underappreciated layer of residual risk.

Clinicians managing MASH should measure Lp(a) at least once in all patients, use it to refine CV risk stratification, and factor it into decisions about therapy intensity. The emerging availability of RNA-targeted Lp(a)-lowering agents makes this measurement increasingly actionable and the fact that resmetirom lowers it is quite compelling