One in Three Overweight MI Patients May Benefit From Semaglutide

In daily practice, many patients with overweight or obesity who have had an MI would potentially benefit from injectable semaglutide (Wegovy; Novo Nordisk), according to a study that applied SELECT trial inclusion/exclusion criteria to a real-world population.

In a finding that has both policy and clinical implications for rolling out the highly popular treatment, researchers found that 31% of patients with a first-time MI within the Western Denmark Heart Registry met eligibility criteria for the trial, which demonstrated that semaglutide reduced MACE by a relative 20% compared with placebo in nondiabetic patients with overweight or obesity and preexisting CVD.

Assuming a similar effect in the SELECT-eligible patients with a prior MI in this Danish cohort, semaglutide would be beneficial with a number needed to treat of 49.

“These results are of paramount importance to regulatory authorities and clinicians when implementing semaglutide in clinical practice,” lead author Malene Hansen, MD (Aarhus University Hospital, Denmark), and colleagues write in a research letter published in the March 5, 2024, issue of the Journal of the American College of Cardiology.

Semaglutide and other glucagon-like peptide 1 (GLP-1) receptor agonists remain costly, and these data showing a high number of patients who are potentially eligible for the treatment will spur additional efforts to identify subsets that stand to gain the most from the therapy, senior author Michael Mæng, MD, PhD (Aarhus University Hospital), told TCTMD. Payers, including governments, will likely decide that treating everyone who is a candidate is not going to be economically sustainable, he said, adding that substudies are ongoing.

But “economy put aside, I would treat all those patients who were actually overweight,” Mæng said, noting that the SELECT patients who received semaglutide at his center “were really happy about the weight loss and were feeling better despite the nausea in the beginning, etc.”

Speaking to the potential reach of such therapy in the future, he added, “In my opinion, this is kind of a statin treatment when the price becomes more affordable for society, but at the moment we will choose who we can afford to pay for.”

In my opinion, this is kind of a statin treatment when the price becomes more affordable for society, but at the moment we will choose who we can afford to pay for. Michael Mæng

For the study, the investigators examined data from the Western Denmark Heart Registry on patients 45 and older who had a first-time MI and documented coronary artery disease on angiography. The analysis looked at 34,405 patients included in the registry between 2010 and 2021.

Overall, 31% were deemed SELECT-eligible, defined as a body mass index (BMI) of at least 27 kg/m² and no diabetes. In the eligible patients, the median age was 64 and the median BMI was 29 kg/m². About one-third (32%) were smokers, and 53% had hypertension.

MACE (MI, ischemic stroke, or CV death) occurred in 10.7% of SELECT-eligible patients during a median follow-up of 5.0 years. Applying the effects of semaglutide seen in the trial, the drug would be expected to lower that rate to 8.7%.

The researchers note that there were several differences between the SELECT participants and the patients from the real-world cohort, with the trial featuring higher BMI, younger age, a lower prevalence of smoking, and a higher rate of hypertension.

“As patient clinical characteristics are heavy determinants of the observed absolute risk, external validity may be threatened,” they write. “Absolute risk estimates from our contemporary cohort may be generalizable to other countries with comparable low cardiovascular disease risk status.”

Commenting for TCTMD by email, Nihar Desai, MD, MPH (Yale School of Medicine, New Haven, CT), pointed out that when it comes to semaglutide, and the GLP-1 receptor agonists in general, “everyone is grappling with the implementation side of addition to our therapeutic armamentarium. We now have a therapy that can reduce cardiovascular events among obese patients with a prior history of cardiovascular disease. This article begins to bring that sort of population health analysis to life—demonstrating the potential impact in Denmark.”

But the proportion of eligible patients likely would apply to a US cohort as well, “and importantly, that number will only increase with time,” Desai said. “Cardiovascular-kidney-metabolic conditions, specifically highlighted in a recent statement from the American Heart Association, are now and will continue to be the dominant drivers of morbidity, mortality, and healthcare expenditures. We need a systematic, coordinated, multistakeholder campaign to address this public health crisis.”

We need a systematic, coordinated, multistakeholder campaign to address this public health crisis. Nihar Desai

Not only do these new findings highlight how common it is to have patients with both obesity and CVD, but also they speak to discussions about how healthcare—particularly the delivery of effective, but high-cost, therapies like semaglutide—is paid for, Desai said.

“In some ways, this case study of semaglutide as well as the SELECT trial illustrate how the misaligned payment system in healthcare can undermine the delivery of care,” he said. Even though semaglutide has been shown to have extensive benefits, he added, “in our system, since the costs are borne by some stakeholders, and the benefits accrue to others, the wide-angle lens that would suggest the development of rational criteria for access (and drug pricing) is abandoned for the clinical status quo—a subset of patients will have access to the drug while many others who would benefit will not.”

Indeed, if all eligible patients identified in this study were to be treated with semaglutide, “that would be a very large cost for the Danish society,” Mæng said. It’s unclear who will be eligible for reimbursed treatment under the government plan, he added, “but I think it will not be that number and it will be a smaller number of patients.”