Coronary Calcium Scoring May Help Get Semaglutide to Highest-Risk Patients

WASHINGTON, DC—The degree of coronary artery calcification (CAC) on imaging may help identify nondiabetic patients with advanced subclinical atherosclerosis and a high body mass index (BMI) who will benefit from taking semaglutide (Wegovy; Novo Nordisk), an analysis of the Multi-Ethnic Study of Atherosclerosis (MESA) suggests.

Assuming treatment effects similar to what was seen in the SELECT trial, the number needed to treat over 5 years to prevent a first obesity-related event—a composite of MACE, heart failure, chronic kidney disease, and all-cause mortality—in this population would be 24 in those with a CAC score of 300 or greater, much lower than the NNT of about 125 observed in those with no CAC.

Increased levels of CAC were most strongly related to risks of MACE and heart failure, Alexander Razavi, MD, PhD (Emory Clinical Cardiovascular Research Institute, Atlanta, GA), reported here at the 2024 Society of Cardiovascular Computed Tomography (SCCT) meeting.

“Overall, these results suggest that among those that meet BMI criteria for GLP-1 receptor agonist and weight-loss-dose semaglutide therapy, there is heterogeneity according to subclinical atherosclerosis burden” and those with the greatest amount of CAC “do derive the greatest benefit from this therapy,” Razavi told TCTMD.

That suggests “we may be able to prioritize those that have a higher subclinical atherosclerosis burden” to receive semaglutide as a primary prevention therapy, he added, noting that the drug has been hard to come by due to shortages and a high cost.

In addition to indications for the treatment of type 2 diabetes and weight management, semaglutide is approved to reduce the risk of MACE in adults with established CVD and either overweight or obesity—ie, secondary prevention.

The current study explores the glucagon-like peptide 1 (GLP-1) receptor agonist’s potential impact in the setting of primary prevention. Razavi noted that prior research has demonstrated that patients with advanced subclinical atherosclerosis—including those with a CAC score of 300 or higher—have a risk of CV events similar to that seen in patients with established CVD.

“Our goal was to look at if there is a benefit of initiating this therapy earlier in the pathophysiology according to subclinical atherosclerosis burden as opposed to waiting [for a patient] to have a heart attack or stroke,” he said.

Applying SELECT Results to MESA

The analysis included 3,129 MESA participants (mean age 61 years; 54% women) who met the BMI cutoff for the SELECT trial (27 kg/m² or higher) and did not have diabetes or clinical CVD. Mean BMI was 32 kg/m².

The presence of CAC was assessed with noncontrast cardiac CT using the Agatston method. Roughly half of patients (51%) had no CAC, with 27% having a CAC score of 1-99, 11% a score of 100-299, and 11% a score of 300 or higher. Mean BMI was relatively consistent across the CAC categories.

The investigators applied the reductions in various outcomes with semaglutide 2.4 mg once weekly observed in SELECT—relative reductions of 20% for MACE, 18% for heart failure, 22% for chronic kidney disease, and 19% for all-cause mortality—to the MESA participants with different levels of CAC.

After adjustment for age, sex, race/ethnicity, hypertension, fasting blood glucose, dyslipidemia, cigarette smoking status, and family history of coronary heart disease, the presence of CAC was associated with greater risks of each of these outcomes, particularly for patients with the largest calcium burden. A CAC score of 300 or higher was most strongly associated with MACE (HR 2.16; 95% CI 1.57-2.99) and heart failure (HR 2.80; 95% CI 1.81-4.35), with a weaker but still significant relationship seen with chronic kidney disease (HR 1.59; 95% CI 1.15-2.22) and all-cause mortality (HR 1.35; 95% CI 1.08-1.69).

The NNT over 5 years to prevent these outcomes varied widely according to CAC status. For MACE, for example, the NNT was over 400 for patients with no coronary calcium but about 50 for those with the highest CAC burden. Similar disparities were seen for the other outcomes as well.

Importantly, Razavi said, the NNT remained below 100 for each outcome among patients with CAC scores of 300 or higher.

Using Coronary CT Angiography for Patient Selection

Commenting for TCTMD, incoming SCCT President Maros Ferencik, MD, PhD (Oregon Health & Science University, Portland), said using coronary CT angiography to assess CAC or other plaque characteristics as a way to influence treatment decisions is a valid approach, one that he has employed when deciding on use of drugs like statins or aspirin. It could also be helpful in enriching populations for clinical trials of medications or interventions, he said.

“What it tells you in clinical practice is that assessment of plaque burden—calcified or noncalcified plaque burden—is a very effective tool in selecting the patients that have the highest risk and will benefit from your intervention most,” Ferencik said, noting that this type of approach has gained support in certain guidelines.

The strategy has benefits from an economic perspective, too, he said, citing the relatively low cost of performing a onetime calcium scan. “To learn how to assign these more expensive medications and find the group of patients that has the largest benefit from taking those medications, that leads to the right allocation of resources for those groups.”

Regarding use of CAC scoring to guide use of semaglutide specifically, Ferencik said it couldn’t be recommended formally until the approach is vetted in additional studies, either randomized clinical trials or prospective registries.

But he also looked at the findings from a broader perspective. “We are actually at the stage where we are equipped to guide the therapies,” said Ferencik, “and as the novel therapies are coming to the field, I think this will be a growing role of cardiovascular CT imaging to help us to select the right patients for the right medications.”

Indeed, Razavi said, this strategy could be used to identify not only which patients should be on a therapy, but also those who don’t necessarily need the treatment.

“I think the flip side of this is also important: to know that the number needed to treat is exceedingly high if your calcium score is 0 despite having a BMI greater than or equal to 27,” he said. “So I think CAC and BMI are complementary in terms of risk assessment. . . . It adds another layer in us being able to initiate this therapy with a little more precision.”