Treatment Gaps Abound in Heart Failure but Can Be Closed, Studies Show

Two studies indicate that there is room for improvement: a GDMT clinic for HF may help increase use of all four drugs.

Treatment Gaps Abound in Heart Failure but Can Be Closed, Studies Show

LISBON, Portugal—The results are mixed when it comes to the application of guideline-directed medical therapy (GDMT) for the treatment of heart failure (HF), two new studies have found, with one showing that efforts to get patients optimized on treatment are inadequate at present and another providing some optimism that the treatment gap can be closed substantially.

Both TITRATE-HF and TEAM-HF, which were presented last week at the European Society of Cardiology (ESC)’s Heart Failure 2024 Congress, suggest there is still room for improvement in GDMT, particularly since patients are infrequently treated with the appropriate dosages, say investigators.

Jasper Brugts, MD (Erasmus Medical Center, Rotterdam, the Netherlands), who led TITRATE, reported that while 44% of patients with HF with reduced ejection fraction (HFrEF) in the Netherlands were treated with all four drug classes making up GDMT, just 1% were prescribed optimal doses.

Justin Ezekowitz, MD (University of Alberta/Mazankowski Alberta Heart Institute, Canada), who discussed the trial following the late-breaking presentation, said these data highlight a “missed opportunity” for appropriate care in a relatively wealthy country with an excellent healthcare system. His own country, he noted, isn’t doing much better. In one recent Canadian study of patients with HFrEF, just 21% were on triple therapy between 2013 and 2018, which is before the introduction of SGLT2 inhibitors.

To address the treatment gap, physicians need to intervene early and not use side effects or contraindications “as an easy way out,” said Ezekowitz. He added that if a patient with de novo HF is going to get onto quadruple therapy, “it’s going to happen early, and it doesn’t happen by chance.”

TEAM-HF was one such trial focused on that type of early intervention, with researchers showing that a program dedicated to optimizing care could get the vast majority of outpatient HF patients on all four drug classes within 12 weeks. After creating a “GDMT clinic” at a single center, the percentage of ambulatory HF patients taking all four drugs increased from 21% to 88% (P < 0.001), with roughly one-quarter titrated to guideline-recommended doses of all four drugs.

Aferdita Spahillari, MD (Duke University, Durham, NC), who led the study along with James Januzzi, MD (Massachusetts General Hospital, Boston, MA), said their study supports the “feasibility of a STRONG-HF-like approach to outpatients GDMT administration for HF.”

What the Guidelines Say

Both the US and ESC guidelines for the treatment of HFrEF recommend a beta-blocker, angiotensin-receptor neprilysin inhibitor (ARNI), mineralocorticoid receptor antagonist (MRA), and SGLT2 inhibitor at target doses for all patients as tolerated. In 2023, based on results from the STRONG-HF trial, a focused update from the ESC recommended starting and uptitrating GDMT within 6 weeks of discharge following a HF hospitalization.

Spahillari said their goal was to determine if a program dedicated to the rapid initiation of contemporary GDMT with all four drug classes was feasible in a general cardiology clinic. For the project, which was launched at Massachusetts General Hospital, ambulatory patients with HFrEF were referred to a newly created GDMT clinic where they met with a nurse practitioner, physician assistant, or pharmacist and were titrated to optimal doses with close monitoring of vital signs and laboratory data. The first and final visits were in person, with interim visits done via telemedicine.

One of the goals of the clinic, said Spahillari, was education so that patients understood why they were taking these drugs and learned that treatment was guided by guidelines and consensus documents. In total, 114 patients were enrolled in the clinic and matched 2:1 to patients treated with usual care.

It’s going to happen early, and it doesn’t happen by chance. Justin Ezekowitz

Over 12 weeks, uptake of four-drug GDMT among those treated at the clinic increased to nearly 90%, while there was no change in the percentage of patients on all four drugs in the usual-care arm. As noted, a little less than 25% of all clinic patients on GDMT reached the target doses of all four drugs. Additionally, the percentage of clinic patients using all four drugs within 50% or more of the target dose increased from 3% to 44%.

Spahillari said they also observed a clinical improvement with greater use of GDMT. Signs and symptoms of congestion significant improved from baseline as indicated by an improvement in NYHA class, a reduction in NT-proBNP levels, and a 30% reduction in the use of diuretics, as well as a reduction in diuretic doses. 

Hospitalization Is an Opportunity

For the Dutch study, Brugts said their research was an attempt to understand how well patients with de novo, chronic, and worsening HFrEF were optimized on GDMT. The national registry included 4,288 patients enrolled between 2022 and 2024 at 48 participating hospitals, which represented more than 70% of hospitals in the Netherlands.

Among 1,732 patients with de novo HF, 50% weren’t taking any of the four HF drug classes prior to the diagnosis. Roughly one-third were on an ACE inhibitor/ARB or ARNI and 33.0% on a beta-blocker, both drugs mostly for the treatment of hypertension. For the 1,860 patients with chronic or worsening HF, 44% were taking all four drug classes, but just 1% were optimized on the target dose. When stratified by hospitals/clinics, there were wide differences in the use of GDMT, ranging from 25% to 75% of patients treated with all four drugs at these sites.  

Brugts said the Netherlands has adopted dedicated, nurse-led HF outpatient clinics, and that these centers fared better than general outpatient clinics when it came to getting patients on all four drug classes. The investigators also assessed what happens during an acute hospitalization for worsening HF and found that 74% of patients had their diuretic changed (or changed dose), just 13.7% were switched from an ACE inhibitor/ARB to ARNI, and 34.2% were started on an SGLT2 inhibitor. 

“Guideline implementation is an opportunity at the hospitalization event,” said Brugts. “It’s not only about diuretics.”

Ezekowitz called the hospital admission a “teachable moment” for clinicians: a chance to get patients optimized on GDMT. While some of the Dutch numbers are still low, he took a somewhat positive view of the changes, noting that switching nearly 14% of patients to an ARNI and getting more patients on an SGLT2 inhibitor “is a lot from a population standpoint.”

Michael O’Riordan is the Managing Editor for TCTMD. He completed his undergraduate degrees at Queen’s University in Kingston, ON, and…

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  • Brugts J. Contemporary guideline-directed medical therapy sequencing and titration in de novo, worsening, and chronic heart failure: first data from the TITRATE-HF study. Presented at: ESC Heart Failure 2024. May 12, 2024. Lisbon, Portugal.

  • Spahillari A. First implementation results from the trial for evaluating guideline-directed medical therapy for heart failure. Presented at: ESC Heart Failure 2024. May 12, 2024. Lisbon, Portugal.

  • Brugts reports speaking and/or advisory board fees from AstraZeneca, Abbott, Bayer, Boehringer Ingelheim, Novartis, and Vifor.
  • Spahillari reports no conflicts of interest.
  • Celutkiene reports personal fees from Novartis, Amgen, AstraZeneca, and Boehringer Ingelheim.
  • Ezekowitz reports research contracts with AstraZeneca, American Regent, Applied Therapeutics, Bayer, Cytokinetics, Merck, Novo Nordisk, and Otsuka.