MINNEAPOLIS — Building on its initial success, researchers expanded a heart failure (HF) guideline-directed medical therapy clinic to treat more people with a wider range of left ventricular ejection fractions (LVEFs). This initiative resulted in a large increase in the proportion of people who achieved three- or four-drug optimal treatment, as well as clinically meaningful improvements in HF symptoms, laboratory and echocardiographic markers, and exercise capacity.

“We saw an improvement in optimal guideline-directed medical therapy from 12% to 91%, and this success came across the spectrum of ejection fractions,” said lead investigator Laura P. Cohen, MD, MPP, cardiologist at Massachusetts General Hospital in Boston.

Specifically, people with LVEF below 50% treated with four-drug guideline-directed medical therapy increased from 14% to 95%, while those with HF with preserved ejection fraction (HFpEF) treated with three-drug guideline-directed medical therapy grew from 6% to 78%.

Quadruple therapy consists of a renin-angiotensin system inhibitor, like an angiotensin receptor-neprilysin inhibitor (ARNI) or angiotensin-converting enzyme (ACE) inhibitor; a beta-blocker; a mineralocorticoid receptor antagonist (MRA); and a SGLT2 inhibitor. Triple therapy includes an ACE inhibitor, an angiotensin II receptor blocker, or an ARNI; a beta-blocker; and an MRA. These regimens can significantly improve survival and quality of life compared with earlier HF treatments, according to previous studies such as STRONG-HF.

Addressing Gaps in Care

“We do an excellent job of treating heart failure patients in subspecialty clinics. However, many patients with heart failure are treated in general cardiology, where the gaps are the largest,” Cohen said during a rapid-fire research session at the Heart Failure Society of America (HFSA) 2025 Annual Scientific Meeting.

Results were published simultaneously in the Journal of Cardiac Failure.

The multidisciplinary guideline-directed medical therapy clinic was established within the general cardiology practice at the Massachusetts General Hospital in 2021. An earlier study showed four-drug guideline-directed medical therapy was implemented in 88% of 114 patients with an LVEF below 50%.

The program expanded to also treat people with HFpEF. The current study included 92 additional patients who were eligible for guideline-directed medical therapy from a cohort of 100 symptomatic HF patients referred to the clinic. These 92 patients had a mean age of 67 years, 25% were women, 10% were Black, and 20% had an LVEF of 50% or greater.

Cohen and colleagues also started measuring “feel and function” outcomes, such as Kansas City Cardiomyopathy Questionnaire (KCCQ) overall summary scores, KCCQ clinical summary scores, and 6-minute walk distance. They also measured changes from baseline to follow-up in New York Heart Association (NYHA) class, N-terminal pro-brain natriuretic peptide (NT-proBNP), and LVEF values.

The baseline and final visits were in-person and included echocardiography. Patients had the option to attend interim visits virtually.

It Takes a Multidisciplinary Team

Patients were treated from September 2023 to May 2025. A dvanced practice providers — a clinical pharmacist, a nurse practitioner, and a physician assistant — saw participants an average of every 2 weeks until they achieved maximally tolerated therapy.

“They learned the nuances of guideline-directed medical therapy administration quickly and have gained expertise and efficiency in delivering it over time,” Cohen told Medscape Medical News. “We also have a clinical nurse who is crucial in helping with between-visit questions.”

“This is a perfect example where a multidisciplinary team can come together to improve care for our patients in need,” she added.

‘Clinically Meaningful Improvement’

“We saw clinically meaningful improvements in all measures,” Cohen said.

Compared with pre-clinic management, findings showed:

• 50% of patients achieved at least 50% of target guideline-directed medical therapy doses.
• 30% achieved optimal guideline-directed medical therapy doses.
• Achievement of guideline-directed medical therapy persisted up to 6 months.
• 6-minute walk distance increased by 37 minutes (P = .04).
• NYHA class I status increased from 2% to over 53% (P < .001).
• LVEF increased from 40% to 50% (P < .001).
• KCCQ overall summary scores increased from 77 to 85 (P = .01).
• KCCQ clinical summary scores increased from 81 to 90 (P = .01).
• Median NT-proBNP decreased from 676 pg/mL to 336 pg/mL (P = .03).

“Not only was our guideline-directed medical therapy clinic effective in improving the guideline-directed medical therapy use and mechanistic outcomes, but it was also safe,” Cohen said.

Four events required urgent care or emergency care evaluation. These included medication-associated hypotension and hypovolemia secondary to SGLT2 inhibitor use, symptomatic hypotension with ARNI initiation, and weakness after a blood draw. One patient was hospitalized for hypotension in the setting of pneumonia and ARNI use.

‘Remarkable Impact’

“This program can serve as a blueprint for scalable, equitable heart failure care. By leveraging advanced practice clinicians and structured follow-up, the guideline-directed medical therapy clinic model bridges the gap between guidelines and improved outcomes,” said Gregg C. Fonarow, MD, Eliot Corday professor of Cardiovascular Medicine and Science and director of the Ahmanson-UCLA Cardiomyopathy Center at the David Geffen School of Medicine at UCLA.

Prior studies have shown intensive guideline-directed medical therapy programs are cost-effective and provide high economic value,” said Fonarow, who was not affiliated with the study. “This can be a win for patients, healthcare delivery systems, and population health.”

This study “showcases the remarkable impact of embedding guideline-directed therapy into an outpatient cardiology practice,” he added. “Almost across the board, symptoms, biomarkers, function, and quality of life improved, with NT-proBNP halving, NYHA class I tripling, and LVEF rising by 10 percentage points on average,” said Fonarow, who is also co-director of the UCLA Preventative Cardiology Program.

Session co-moderator Arvind Bhimaraj, MD, MPH, of the Houston Methodist Specialty Physician Group, Houston, asked about the cost implications.

“It’s something we’re thinking about, especially the chronic care management portion,” Cohen said. Currently, the clinic bills for the clinic and follow-up visits. The next step, she said, is a cost-effectiveness analysis that includes money saved from avoiding hospitalizations.

Session co-moderator Katherine Faulkner, PharmD, also asked about patient response.

“I think patients really like the interaction with the providers, the close follow-up, and having an educational component helps to really drive home why and helps them understand the data,” Cohen said.

“It’s why we are so gung ho about getting them on guideline-directed medical therapy.” 

This work was supported by an unrestricted grant from AstraZeneca Pharmaceuticals. Cohen disclosed having a relationship with Kento Health. Bhimaraj had participated in advisory boards of Abiomed/J&J and received speaker fees from Maquet and Abbott. Fonarow and Faulkner reported having no relevant conflicts of interest.

Damian McNamara is a freelance writer for Medscape Medical News. He worked full-time for Medscape and WebMD from 2018 to 2024. McNamara has a BA in chemistry and an MA in science, health, and environmental reporting/journalism. He works out of a home office in Miami, with a 100-pound chocolate lab known to snore under his desk during work hours.