Will Semaglutide Change Cardiac Surgery? It Already Has

LISBON, Portugal—One of the first presentations at Europe’s annual cardiothoracic surgery conference was not about a new technique or device, but whether the revolutionary obesity medications targeting the glucagon-like peptide-1 (GLP-1) receptor will change the landscape of surgical practice.

The answer seems to be a resounding yes.

“Some stories are too good to be true, right? But this might not be one of those stories,” Subodh Verma, MD, PhD (St. Michael’s Hospital, Toronto, Canada), who gave a talk on the subject here today at the European Association for Cardio-Thoracic Surgery (EACTS) annual meeting. “All of the signals seem to be pointing in the right direction in terms of mortality and morbidity” for drugs like semaglutide (Novo Nordisk), he told TCTMD. “The safety in the large trials seems to be very good in terms of adverse events.”

Initially developed for the treatment of type 2 diabetes, the GLP-1 receptor agonists have been riding a wave of data published over the past couple of years showing a reduction in CV events among nondiabetics, improvement in symptoms and rapid weight loss in patients with heart failure with preserved ejection fraction (HFpEF), and a likelihood of positive effects beyond weight loss, to name a few.

“Although it is early days, it could be speculated that if access to this therapy becomes more open, that rates of coronary revascularization should change over the next several years,” Verma said during his presentation. While his presentation focused on coronary surgeries—the theme of the session—he acknowledged that these medications could have an impact on others, including heart transplant.

Sigrid Sandner, MD (Medical University of Vienna, Austria), who co-chaired the session, is also a believer, telling TCTMD that semaglutide will “absolutely” change the landscape of cardiac surgical practice.

Other cardiac surgeons, however, might not fully appreciate how the advent of these powerful medications will affect their practice, according to Michael Borger, MD, PhD (Heart Center of Leipzig, Germany), who served as a panelist during the session. “It definitely is going to change the face of cardiac surgery,” he commented to TCTMD. “Unfortunately, most cardiac surgeons don't realize that. . . . This is not knowledge that is diffused into the cardiac surgery community.”

More specifically, Borger said, increased use of these medications will likely mean fewer CABG patients down the line, but it’s uncertain if there will be a similar impact on heart failure patients requiring CV surgery. These patients may be an exception since some “will eventually develop those complications and will eventually require LVAD or transplant,” he said. It’s also possible that their heart failure would be so aggressive that drugs such as GLP-1 receptor agonists, as well as the guideline-recommended SGLT2 inhibitors, wouldn’t have a large enough effect to prevent the need for surgery. Borger added that he is “skeptical” of how use of these drugs will change valvular surgical practice down the road.

To TCTMD, Mario Gaudino, MD, PhD (Weill Cornell Medicine, New York, NY), predicted semaglutide will change the field in two different ways. “It will change the patient population [as] most likely less patients will need bypass surgery, which is good because medicine [should] always go toward prevention, not treatment,” he said. “But also, [it will] improve the outcome of bypass surgery.”

Lots of Data

During his talk, Verma outlined all of the available evidence around semaglutide, including a recent analysis showing similar effects in men and women with HFpEF.

Some have likened GLP-1 drugs to statins in how drastically they improve a swath of outcomes across a broad spectrum of patients, he said. Whether they affect rates of atherosclerosis is still being investigated, though “there's a lot of biology to suggest that they directly affect the vessel wall and processes involved in atherothrombosis, which coupled with the so-called indirect effects that we all have come to know about—weight reduction, blood pressure reduction, and improvement in glycemia—could tilt the balance in favor of an anti-atherosclerotic effect,” Verma explained.

Other data have shown a greater degree of weight loss in women compared with men along with a greater reduction in CRP but similar rates of MACE, “emphasizing that these benefits are not necessarily seen in parallel with the degree of weight loss,” he said.

While no CABG-specific data yet exist, Verma said that these analyses will be presented next month at the American Heart Association Scientific Sessions.

As for heart failure, he showed several studies linking semaglutide to improvement in hard endpoints as well as less inflammation and better left atrial remodeling in patients with HFpEF.

“This raises the tantalizing hypotheses that this therapy may not only change the landscape of revascularization, but may also potentially change the outcomes of incident atrial fibrillation,” Verma said. The drugs may also have “many other unique attributes that may not necessarily be germane to our day-to-day practice as heart surgeons, but are certainly germane to people living after heart surgery, [such as] complications of sleep apnea and other addictive behaviors such as smoking.”

Wisdom for Operators

In response to an audience question regarding whether preoperative use of semaglutide could lead to safer operations, Verma said “prehab” could become a more regular practice, potentially leading to improved physical activity capacity prior to surgery. “The challenge in doing that is that many centers and many patients don't have the luxury of a 3-month waiting period” given how long it takes to get to a target dose with these drugs, Verma explained. “But the general concept of using strategies prehab to increase VO2 as a measure then to then see outcomes improve is a really exciting one.”

During the session, Borger asked about the potential for aspiration following gastroparesis and if surgeons should have any concerns there.

In fact, the American Society of Anesthesiologists published a guidance document recommending stopping GLP-1 inhibitors 1 week before surgery for patients on weekly dosing. Verma told TCTMD this was likely based on two reported cases of aspiration and said he follows this guidance—resuming semaglutide after oral intake is reestablished, generally at around 4 weeks postop.

Verma acknowledged that cost and accessibility remain hurdles for these drugs, though he urged cardiac surgeons to become more knowledgeable about their benefits so they can convey that information to patients. While GLP-1 receptor agonists are part of a chronic disease management strategy, they should not replace good lifestyle choices, he stressed.

“The key message is that at the heart of semaglutide is much more than weight,” Verma said. “People think that it's a medication for weight loss, but it's not. It's a disease-modifying therapy for atherosclerosis. It's a disease-modifying therapy for heart failure. It's a disease-modifying therapy for liver disease. It's an anti-inflammatory strategy. And it also offers weight loss. And I think that needs to be part of our vernacular.”

For cardiac surgeons, Verma advised understanding that “pharmacology matters to long-term outcomes, and . . . understanding that this should be part and parcel of the cocktail of secondary prevention is key.”