Among patients without diabetes or cardiovascular disease and with a BMI ≥27 kg/m², those with coronary artery calcium (CAC) scoring ≥300 derive the largest benefit from a weight-loss-dose of semaglutide for the prevention of major adverse cardiovascular events (MACE), according to an analysis published in JACC: Cardiovascular Imaging.

Alexander C. Razavi, MD, MPH, PhD, and colleagues examined data from 3,129 participants from the MESA study who met BMI criteria for semaglutide (≥27 kg/m²) and who underwent noncontrast cardiac CT for CAC scoring. Their mean age was 61.2 years, 54% were female and 62% were non-White. Mean BMI was 31.8 kg/m² and 51% of participants had a CAC score of 0 and the score was 1-99 for 26%, 100-299 for 11% and ≥300 for 11%.

The researchers assessed the association between CAC and MACE, heart failure (HF), chronic kidney disease (CKD) and all-cause death. Risk reduction estimates from the SELECT trial were used to calculate the number needed to treat across CAC burden categories.

Results showed that rates of MACE, HF, CKD and all-cause mortality increased as the CAC score increased when stratified by the baseline BMI. For MACE, a 2.2-fold higher risk was found for a CAC ≥300 compared with CAC = 0 (hazard ratio, 2.16; 95% CI, 1.57-2.99; p<0.001). When comparing CAC ≥300 with CAC = 0, the hazard ratio for HF was 2.80 (95% CI, 1.81-4.35; p<0.001), for CKD 1.59 (95% CI, 1.15-2.22; p=0.006) and all-cause mortality 1.35 (95% CI, 1.08-1.69; p=0.009).

Additionally, when comparing the CAC = 0 and CAC ≥300 burden categories, the difference in the number needed to treat at five years was large: MACE (653 vs. 79), HF (1,094 vs. 144), CKD (1,044 vs. 144) and all-cause mortality (408 vs. 98), respectively.

Noting the stepwise higher risk for MACE, HF, CKD and all-cause mortality across the CAC strata in these patients without diabetes, the authors state the results have clinical implications for patients with advanced subclinical atherosclerosis too. "Overall, our study reinforces the value of CAC scoring in personalizing preventive strategies but also highlights the potential of semaglutide therapy in mitigating the broad spectrum of cardiovascular-kidney-metabolic risk," they write.

In an accompanying editorial comment, Robert A. Kloner, MD, PhD, FACC, and Matthew J. Budoff, MD, FACC, write that "prescribing semaglutide for primary prevention to those individuals with elevated BMI and CAC appears to be the best approach for improving outcomes, especially in the setting of limited availability of the drug or in situations where cost and lack of insurance is an issue."

Keywords: Cardiovascular Diseases, Coronary Vessels, Atherosclerosis