Late-breaking cardiovascular drug trials took center stage at ACC.25
Progress in the world of cardiovascular pharmacology made headlines at ACC.25, the annual meeting of the American College of Cardiology (ACC), with late-breaking trials unveiling new therapies, repurposed medications and promising advancements in long-standing treatment gaps. Cardiovascular Business spoke with Richard Kovacs, MD, chief medical officer of the ACC and a former ACC president, to learn more.
"We're always glad to see more drugs being developed for cardiovascular indications, but sometimes we've had years go by without much action, so this year was really great. The late-breakers I would lump them into three categories. The first bucket is an extension of what we're using for metabolic and chronic kidney disease and weight loss. The second is some new applications for old drugs, and then third is some really new things that are coming out," Kovacs, a professor of clinical medicine with the Indiana University School of Medicine, explained.
Semaglutide Headlines with STRIDE and SOUL trials
Two key late-breakers focused on the the GLP-1 receptor agonist semaglutide, which adds to what Kovacs called a "tsunami of cardiometabolic drugs" into the cardiovascular space in recent years.
Among the most talked-about trials was STRIDE, which showcased the first meaningful therapy in over two decades for patients with peripheral artery disease (PAD). The GLP-1 receptor agonist semaglutide significantly improved symptoms and walking distance in patients with claudication.
"This is the first time where we have a new drug for peripheral vascular disease that improves symptoms and walking distance. I think stride is the most impactful trial because we see so many patients who have PAD who have claudication, and now we have something that for the first time in over 20 years to treat them with that makes a difference in symptoms," Kovacs said.
He added that cardiologists want additional tools in their toolbox to help address large disparities in PAD care, where a high percentage of patients with advanced critical limb ischemia requiring amputation are Black. This may be one way to help bridge the gap in relieving symptoms.
The SOUL trial also made headlines, presenting the first cardiovascular outcomes data for oral semaglutide. While the effects appeared modest compared to the better bioavailability of the drug using injectable formulations, Kovacs noted the significance of a pill-based option.
"They are just some people who are just afraid of needles, and so having an oral option is a good option," he said, highlight the trial data.
The growing presence of GLP-1 receptor agonists such as semaglutide across cardiology conferences is no accident. Former diabetes and obesity drugs caused harm to the heart, so the FDA asked that all new agents have long-term cardiac safety monitoring, and the basic sciences hinted there may be benefits beyond their initial indications, he explained.
"In long-term cardiovascular outcomes trials to test the safety of these drugs we are now seeing beneficial effects, and it's just great to see this evolve over time, but we need to understand the mechanisms behind it and pick the right patients for the right therapies," Kovacs said.
Old drugs, new tricks in Api-CAT and WARRIOR
Repurposing familiar drugs for new indications was another theme. The API-CAT trial explored low-dose apixaban in cancer patients with venous thromboembolism (VTE), including deep venous thrombosis and pulmonary embolus, demonstrating comparable efficacy to standard dosing, but with lower bleeding risks.
"We can go with a lower dose of apixaban and get the same efficacy. So that was a real nice extension of an already familiar drug to us.
Meanwhile, the WARRIOR trial focused on intensive medical therapy (IMT) using high-intensity statins, maximally tolerated ACEs or ARBs in women with ischemia with no obstructive coronary artery disease (INOCA). The trial was neutral and did not reduce the first occurrence of all-cause death, myocardial infarction, stroke or hospitalization for worsening angina or heart failure.
However, Kovacs said presenter Eileen Handberg, PhD, a professor of medicine with the University of Florida, was careful to point out that this does not mean doctors should discontinue statin and ACE/ARB medications among women with risk factors. She said ongoing ancillary CCTA imaging and biorepository studies will continue to contribute to improve our understanding of this growing patient population and its symptom burden.
Kovacs did praise the trial for keeping attention on an often-overlooked group.
Breaking ground with new cardiovascular therapies
In the “new frontiers” category, lorundrostat, an aldosterone synthase inhibitor, demonstrated impressive blood pressure reduction in a phase 2B trial for patients with resistant hypertension. While dose optimization remains a work in progress, Kovacs sees potential.
"I think lorundrostat is going to be very interesting so that we have another drug for hypertension. Hypertension in the United States is under-recognized and under-treated, and that resistant and truly refractory population is one where we really need more classes that are effective for blood pressure." Kovacs said.
Another notable trials was REVERSE-IT for bentracimab, a monoclonal antibody fragment that can reverse the effects of ticagrelor in cases of major bleeding. Kovacs said this new data is impactful for treating patients on this antiplatelet agent.
"It's nice to have that tool in your toolbox when people are bleeding in the middle of the night," he explained.
Find more key late-breakers from ACC.25 in the video Key takeaways from ACC.25: Advances in cardiovascular science and on our ACC coverage landing page.
Dave Fornell has covered healthcare for more than 17 years, with a focus in cardiology and radiology. Fornell is a 5-time winner of a Jesse H. Neal Award, the most prestigious editorial honors in the field of specialized journalism. The wins included best technical content, best use of social media and best COVID-19 coverage. Fornell was also a three-time Neal finalist for best range of work by a single author. He produces more than 100 editorial videos each year, most of them interviews with key opinion leaders in medicine. He also writes technical articles, covers key trends, conducts video hospital site visits, and is very involved with social media. E-mail: [email protected]