Exploring the 'new era' of HFpEF treatment: More options exist, but challenges remain
Just a few years ago, there were few treatment options for patients with heart failure with preserved ejection fraction (HFpEF), but that has changed with several new drugs. At the American Heart Association (AHA) 2024 meeting, Clyde Yancy, MD, MSc, professor and chief of cardiology with Northwestern Medicine and a former AHA president, spoke with Cardiovascular Business about the excitement in cardiology over these advances.
HFpEF, characterized by normal ejection fraction but impaired heart relaxation, accounts for a growing proportion of heart failure cases. The condition has historically been challenging to treat, but recent breakthroughs are reshaping the landscape. However, treatment according to guidelines were sparse, limited to just diuretics to control symptoms and reduce the blood pressure.
"Just a few years ago, we questioned if HFpEF was even a distinct condition," Yancy explained. "For decades, treatment options were limited to managing associated conditions like hypertension and atrial fibrillation. This changed with a wave of new clinical study evidence demonstrating the efficacy of specific therapies targeting HFpEF. But the science has really come along quite nicely ... now we're at a point where we have multiple agents to treat the condition."
He said HFpEF represents the kind of heart failure cardiologists see on a regular basis. In the past, there was a focus on treating the accompanying illnesses, but Yancy said the science has changed that view and the good news is that there is a growing list of drug therapies now available.
Promising new therapies for HFpEF
Yancy described this as a "new era" in HFpEF treatment, with four major therapies emerging:
SGLT2 inhibitors: Initially developed for diabetes, sodium-glucose co-transporter-2 inhibitors have demonstrated significant benefits in heart failure patients, including those with preserved ejection fraction. He said these agents were the first to show definitive improvements in outcomes.
Mineralocorticoid receptor antagonists (MRAs): The nonsteroidal MRA finerenone has shown promise in reducing the burden of symptoms and hospitalizations for HFpEF patients, marking another significant advance.
Incretin Therapies: Dual incretin agonists, as presented in the late-breaking SUMMIT trial at AHA 20243, offer compelling evidence of symptom relief and reduced hospitalization risk. This builds on earlier data supporting GLP-1 receptor agonists like semaglutide.
Combination approaches: By integrating these therapies into a cohesive treatment algorithm, clinicians can now employ a triple therapy for HFpEF, which Yancy said is a stark contrast to the limited options available just a few years ago.
"This really is a new day, a new era for heart failure, and I'm really pleased," Yancy said of these advancements.
Challenges and opportunities in HFpEF
Despite these advances, gaps remain. He said there is opportunity for more discovery to try to fill out the portfolio of therapies that not only change the symptom burden and the hospitalization frequency, but the risk of death.
"The key takeaway is that we need to do more and learn more. We have yet to identify an agent that changes HFpEF cardiovascular mortality. The other agents we have for heart failure with reduced ejection fraction (HFrEF) actually change cardiovascular mortality. That is still a conundrum," Yancy said.
At the AHA meeting, he said new science was presented that begins to explore very new therapies that might have a greater impact. He said research areas include looking at the role of inflammatory and using "inflammasome" drugs as a novel treatment. There are also still questions if implantable device therapy can play a roll in HFpEF.
Educating clinicians about HFpEF is another priority. Historically the condition has been underdiagnosed due to difficulties in diagnosis and the limited treatment options, but HFpEF is now a condition for which targeted therapies exist. Yancy emphasized the importance of "alerting practitioners" to recognize and treat this prevalent condition.
Looking to the future and addressing barriers in therapy
While these therapies represent a significant leap forward, questions of access and affordability remain. Many of these treatments are proprietary, posing cost barriers for widespread adoption. Still, the potential to improve the lives of millions of patients makes these challenges worth addressing.
"There will be some challenges with access that we have to navigate. But nevertheless, there's a way to help millions of patients feel better. We shouldn't miss that opportunity. So that's why, again, I say we need to educate, but we also need to alert. We have an action item and we could do some things about this," Yancy explained.
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: dfornell@innovatehealthcare.com