AHA Scientific Sessions 2026 Abstract · Nov 2, 2026
Cardiometabolic Outcomes of Resmetirom Modeled Projection of Atherosclerotic Cardiovascular Disease Risk Reduction: Systematic Review and Meta-Analysis
By Alper A, Karthikeyan A, Fagin A et al.
Background: Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of mortality in patients with metabolic dysfunction-associated steatotic liver disease (MASLD). Resmetirom, a thyroid hormone receptor-β agonist approved by the FDA for MASH, improves liver histology and lipid profiles; however, its aggregate effect on atherogenic lipoproteins and projected ASCVD risk reduction remains unquantified. Methods: We conducted a systematic review and meta-analysis of randomized, placebo-controlled trials of resmetirom reporting cardiometabolic outcomes (search date: April 25, 2026). Mean differences were pooled using inverse-variance random-effects models. Outcomes included LDL-cholesterol, apolipoprotein B, apolipoprotein C-III, lipoprotein(a), blood pressure, heart rate, body weight, and HbA1c. Projected 10-year ASCVD risk reduction was modeled using three peer-reviewed frameworks anchored to baseline risk derived from the AHA 2023 PREVENT equations. Results: Four trials (n=1,996) met inclusion criteria. Resmetirom significantly reduced LDL-cholesterol by 15.21% (95% CI -18.99 to -11.43; I ² =37%; p<0.00001), apolipoprotein C-III by 23.81% (95% CI -29.65 to -17.96; I ² =42%; p<0.00001), and lipoprotein(a) by 25.07 nmol/L in patients with baseline Lp(a) >10 nmol/L (95% CI -35.02 to -15.12; I ² =56%; p<0.00001). ApoB was reduced by 20.34% in those with baseline LDL-cholesterol >100 mg/dL (95% CI -26.55 to -14.13; I ² =60%; p<0.00001). Systolic and diastolic blood pressure fell by 3.08 mmHg (95% CI -4.60 to -1.57; p<0.0001) and 1.74 mmHg (95% CI -2.92 to -0.56; p=0.004), respectively, with no heterogeneity (I ² =0% for both). HDL-cholesterol, body weight, heart rate, and HbA1c were not significantly altered, and no excess of major adverse cardiovascular events was observed. Projected relative risk reductions ranged from 2.3% under an Lp(a) model (NNT ¹ ⁰ ᵧ 315) to 19.3% under an apoB model (NNT ¹ ⁰ ᵧ 37), with estimates of 9.8% (NNT ¹ ⁰ ᵧ 73) and 11.8% (NNT ¹ ⁰ ᵧ 60) under LDL-cholesterol and combined models, respectively. Conclusions: Resmetirom produced consistent reductions across atherogenic lipoprotein fractions and modest blood pressure lowering, without adverse effects on body weight, heart rate, or glycemic control. Modeled through validated epidemiological frameworks, these effects project a 10-19% relative reduction in 10-year ASCVD risk. Definitive confirmation awaits the MAESTRO-NASH-OUTCOMES trial.