‘Provocative’ Projections See Semaglutide Slashing CV Events in Adults With ASCVD

Once-weekly semaglutide 2.4 mg (Wegovy; Novo Nordisk), if used in US adults with atherosclerotic cardiovascular disease (ASCVD) who meet the criteria of the SELECT trial, could prevent nearly half a million major adverse cardiovascular events over the next decade, researchers project.

Assuming an effect similar to what was seen in the trial—a 20% relative reduction in risk of MACE (MI, stroke, or CV death) and a 19% relative reduction in risk of all-cause death—use of the glucagon-like peptide-1 (GLP-1) receptor agonist would be expected to stave off about 496,000 MACE and more than 159,000 non-CV deaths, according to a study presented as a poster at the recent 2024 American Diabetes Association Scientific Sessions.

“I’m always interested in the potential public health impact of new therapies [and] given the impressive results from SELECT, we were interested in what that could potentially translate to in the US population,” senior author Ann Marie Navar, MD, PhD (UT Southwestern Medical Center, Dallas, TX), told TCTMD via email.

She said she wasn’t surprised by the findings considering the high prevalence of overweight and obesity, adding that “seeing the numbers gives me hope that we can start to bend the curve for ASCVD at a population level.”

For the study, presented by lead author Mads Faurby, MSc (Novo Nordisk, Plainsboro, NJ), the researchers identified US adults who would have met criteria for inclusion in the SELECT trial using data from the National Health and Nutrition Examination Survey. Eligible patients were those who were at least 45 years old, had a history of ASCVD (MI, stroke, or PAD), had a body mass index (BMI) of at least 27 kg/m², and did not have diabetes.

As of 2023, more than 6.1 million US adults (mean age 67 years; 43.6% women) would have been eligible for the trial. Mean BMI was 32.6 kg/m², and 58% had a history of CAD, 51% MI, 48% stroke, and 23% PAD.

Using the SMART2 risk calculator, the investigators estimated that 41% of these individuals would have at least one MACE over the next 10 years, with a total of more than 3 million projected events. That included about 1.3 million MIs, 674,000 strokes, and 1.1 million CV deaths, along with more than 1 million non-CV deaths.

Based on the effects observed in the SELECT trial, if this cohort were treated with semaglutide 2.4 mg, there would be about a 16% reduction in overall MACE and total deaths over 10 years. That includes a 16% lower risk of each of the individual components of MACE and a 15% reduction in non-CV deaths.

Commenting for TCTMD, Nathan Wong, PhD (University of California, Irvine), noted that these figures are based on the assumption that all of these individuals will be able to access the medication and adhere to it over the long term. He pointed out that cost issues and side effects may influence the ability of patients—particularly those from higher-risk, underserved populations—to remain on treatment.

“It is a best-case scenario, but I think it’s provocative data and, in my opinion, it should be a call to action for the manufacturers and all those involved to make these therapies accessible and affordable to all who could potentially benefit from them,” Wong said.

In order to improve accessibility to medications like semaglutide, which are more expensive in the US than elsewhere in the world, there needs to be more transparency about pricing, Wong said. In addition, he suggested that programs should be set up to ensure access to underserved populations with high rates of obesity and cardiovascular disease.

Moreover, Wong said, “cardiologists need to embrace these therapies as part of their armamentarium to reduce residual cardiovascular disease risk now that the SELECT trial has proven, at least in the case of semaglutide 2.4 mg, that this therapy can substantially reduce not only future cardiovascular event risk but also future risk of developing diabetes in our cardiovascular patients with obesity.”

Navar touched on that idea as well. “In the popular media, the general population is only hearing about semaglutide as a weight-loss drug,” she said. “As a preventive cardiologist, I see it as a drug to prevent cardiovascular events. I think we need to pay more attention to the cardiovascular benefits of the drug and focus less on weight.”

She acknowledged the challenges that remain in terms of accessing semaglutide, including manufacturing shortages, high co-pays, and other obstacles imposed by pharmacy benefit managers, like the requirement for prior authorization.

“I am hopeful that many of these challenges will start to abate with time, but I think we’ll have to be patient,” Navar said.