Panel Outlines Updates on HF Treatment Developments, Recommendations for Guidelines

In a pair of presentations at the 5th annual Heart in Diabetes Conference, hosted by The Metabolic Institute of America, John McMurray, MD, outlined recent developments in therapy for heart failure with preserved ejection fraction (HFpEF) and heart failure with reduced ejection fraction (HFrEF), and Javed Butler, MD, offered insights on what the management of HF should look like.

HFpEF and HFrEF

When it comes to HFrEF, “we have a lot of new evidence about the management of these patients pharmacologically. In fact, there are 4 trials that have been positive in just the past 2 years,” said McMurray, who is a professor of medical cardiology and clinical deputy director of the Institute of Cardiovascular and Medical Sciences at Queen Elizabeth University Hospital in Glasgow, Scotland.

Positive trial results have been seen among both inpatient and outpatient individuals. Citing data from DAPA-HF and EMPEROR-Reduced, McMurray walked through the benefits of sodium-glucose cotransporter 2 (SGLT2) inhibitors in those hospitalized with HFrEF. Specifically, data from these trials showed “very statistically significant and consistent benefits…[and] consistent benefit in patients with and without type 2 diabetes,” McMurray said.

In addition, findings of DAPA-HF and EMPEROR-Reduced also underscored the renal benefits of SGLT2 inhibitors in these patients, as the treatments resulted in reduced rates of decline in estimated glomerular filtration (eGFR) over time.

“These treatments reduce death, they reduce hospitalization, they improve symptoms, and they reduce the rate of decline in kidney function in patients with HFrEF,” McMurray stressed. “Therefore, not surprisingly just in the past few days, in the new European Society of Cardiology heart failure guidelines, you can see that SGLT2 inhibitors have been given a class one level, a recommendation, they are now regarded as a pivotal lifesaving therapy in patients with HFrEF,” he said.

For patients with HF and mid-range or mildly reduced ejection fraction, or HFpEF, McMurry discussed 2 recent breakthroughs in treatment. “One is an extension of the approval for sacubitril/valsartan (Entresto) based on the PARAGON-HF trial where it seemed as though sacubitril/valsartan data benefits in patients with an ejection fraction up to approximately 60%,” McMurray said.

Second were findings of EMPEROR-Preserved, the sister trial of EMPEROR-Reduced, which was the first clinical trial to successfully show that a therapy (empagliflozin) can cut the risk of hospitalization and cardiovascular death for patients with HFpEF.

“In patients with heart failure and an ejection fraction above 40%, empagliflozin compared to placebo significantly reduced the composite primary outcome cardiovascular death, or heart failure hospitalization by 21%, a highly statistically significant benefit, again that was observed very early after starting treatment,” McMurray explained.

Several new trials have also been conducted to assess patients with HF who have been hospitalized because of decompensation, including SOLOIST-Worsening Heart Failure, which studied the effects of sotagliflozin—an SGLT1/2 inhibitor. Results are also expected from the DAPA Acute HF-Thrombolysis in Myocardial infarction 68 trial.

Additionally, intravenous iron therapy marks an important option for ambulatory patients, as it helps improve symptoms, quality of life and functional capacity. “We didn't know whether intravenous iron therapy reduced morbidity and mortality, but this was recently studied in hospitalized patients with decompensated HF….There was a significant and relatively substantial 26% relative risk reduction in heart failure hospitalizations,” McMurray said. However, this was a smaller trial, and 3 additional trials are underway to better assess this therapy.

Overall, “We've made dramatic progress in HFrEF, and even more recently in HFpEF and it really has been a most exciting time for heart failure and for our patients with heart failure,” McMurray concluded.

HF Guideline Recommendations

In his talk, Butler, a professor of medicine at the University of Mississippi Medical Center in Jackson, Mississippi, offered his opinion on what the guidelines for the management of HF should entail.

Prior to offering his insights, Butler offered a disclaimer acknowledging “the fact that the guidelines are very evidence-based and they try to keep opinion-based recommendations to the minimum and try to go with the highest level of evidence.”

While the use of SGLT2 inhibitors focuses on the treatment of HF, Butler underscored the numerous trials that highlight the preventive nature of these pharmacotherapies and argued for increased use to prevent HF initially, rather than solely for symptom mitigation.

“We really have neglected prevention of HF quite a lot and our guidelines are primarily focused on treatment of HF, per se. I think a very dedicated segment on prevention of HF in the guidelines would be great,” he explained, noting this does not have to only involve use of SGLT2 inhibitors. “Just a focus of lifestyle management, low salt diet, exercise, diet, activity level, blood pressure,” could be beneficial.

In the past, all trials involving patients with acute HF have failed, leading to opinion-consensus based management strategies included in guidelines, Butler said. These included patient education, transitions of care, and early follow-up.

However, several recent trails have been positive in that space (ie, Vericiguat: Victoria, AFFIRM-AHF, PARADIGM-HF).

“Beyond prevention, the second area that I think which is prime to have dedicated focus in the guidelines is the area of acute heart failure and worsening heart failure,” Butler said. “We are not living in the data-free zone anymore and I think putting those things together will be very interesting.”

Furthermore, important data regarding quality of life warrant an inclusion of “a more focused quality of life-based recommendation, and not only the traditional mortality, morbidity based recommendations,” in the guidelines, he said.

Butler also pointed out the use of devices in patients with HF is somewhat neglected. Despite the active nature of the field, Butler explained that guidelines traditionally incorporate data from typical pharma trials which includes information on mortality and morbidity from thousands of patients, while device trials are usually relatively small.

“I think some really thoughtful minds will have to come together and try to figure out how to incorporate all of this device data in the management of patients with HF, especially those patients that are failing traditional pharmacologic therapy.”

Although the prognosis for HF is comparable to that of many forms of cancer, Butler noted that the level of urgency or drive often seen when treating those with cancer is largely absent when it comes to addressing HF.

“There are huge gaps in terms of optimization of therapy, gaps big enough that cannot be explained just by insurance and cost and tolerability and contraindications,” he said, adding “why does it take us months and years to start these lifesaving medications in patients with HF, when we know that the benefits are relatively very early on?”

Not only should the guidelines include the above recommendations, but they should offer providers the flexibility in treatment sequencing and “basically give a roadmap of implementation of the therapies,” Butler concluded.