Diabetes Drug May Benefit All Heart Failure Patients

BOSTON — Researchers from Brigham and Women’s Hospital have uncovered new evidence that shows drugs originally developed to treat type 2 diabetes may benefit a wide range of patients with heart failure. 

The research was presented at the recent European Society of Cardiology conference and published simultaneously in The New England Journal of Medicine and The Lancet.

It stems from the largest trial to date of heart failure patients with mildly reduced or preserved ejection fraction.

During that trial, the Brigham and Women’s Hospital researchers, in collaboration with a team from the University of Glasgow, in Scotland, showed that dapagliflozin, which had previously been shown to benefit patients with heart failure with reduced ejection fraction, is likely to also reduce cardiovascular death and hospitalization for patients with mildly reduced or preserved ejection fraction — a population of millions of patients who have had limited therapeutic options in the past. 

A meta-analysis that included two clinical trials further strengthened the evidence that this class of drugs may provide protection for a wide range of heart failure patients.

“In the largest and most inclusive trial of heart failure with mildly reduced or preserved ejection fraction, we found that treatment with the SGLT2 inhibitor dapagliflozin can benefit patients across the full spectrum of heart failure,” said Dr. Scott Solomon, of the Brigham’s Division of Cardiovascular Medicine. 

“These findings establish SGLT2 inhibitors as foundational treatment for patients living with heart failure, regardless of ejection fraction, to help prevent hospitalization and morbidity and to extend meaningful survival and improve health-related quality of life. These are the outcomes that matter most to patients and to clinicians — to keep patients feeling well and living longer,” he said.

Dapagliflozin is a sodium-glucose co-transporter-2 inhibitor — a class of drugs that cause the body to excrete sugar in urine. 

In addition to controlling blood sugar in patients with diabetes, SGLT-2 inhibitors have been shown to provide significant cardiovascular and kidney disease benefits. 

The trial, which was conducted at 353 sites across 20 countries, was designed to determine whether dapagliflozin would decrease cardiovascular morbidity and mortality in patients with heart failure with mildly reduced or preserved ejection fraction. 

The trial enrolled patients who were 40 or older and had symptomatic heart failure with an ejection fraction of greater than 40%, including mildly reduced ejection fraction and preserved ejection fraction, as well as patients who had previously had reduced ejection fraction that had improved to greater than 40%, and in both the outpatient and inpatient setting. 

More than 6,000 participants were randomized to receive dapagliflozin or placebo and followed for a median of 2.3 years. The primary endpoint was a composite of cardiovascular death or worsening heart failure.

Dapagliflozin significantly reduced the primary composite endpoint by 18%. Worsening heart failure occurred in 368 participants (11.8%) in the dapagliflozin group compared to 455 participants (14.5%) in the placebo group. 

Cardiovascular death in these groups occurred in 231 (7.4%) and 261 (8.3%) participants, respectively. Key secondary outcomes were also significantly reduced, including total heart failure hospitalizations and total symptom burden.

The authors note that the work has some limitations. Less than 5% of patients enrolled in DELIVER were Black, and the COVID pandemic limited symptom assessment after March 2020.

“There are more than 64 million people worldwide affected by heart failure, half of whom have mildly reduced or preserved ejection fraction,” said Solomon.

“Our goal is to rigorously and scientifically evaluate potential treatments so that we can provide the best evidence-based care to help them lead longer, healthier lives.”

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