SGLT2 Inhibition in Acute Decompensated Heart Failure: Another Win for this Remarkable Class of Medications

By Mark H. Drazner, M.D., M.Sc.

Professor of Internal Medicine
Clinical Chief of Cardiology

Some key sessions at #AHA21 were rebroadcast for international audiences at times more favorable for time zones outside the United States. As part of those rebroadcasts, live commentary was added following the recorded session. I had the honor of being one such commentator for a key late-breaking science session that was rebroadcast in Japan.

While there were four very interesting trials presented in that session, I would like to highlight the discussion focused on EMPULSE (Empagliflozin in Patients Hospitalized for Acute Heart Failure). This trial tested whether empagliflozin 10 mg, an SGLT2 inhibitor, when started within one to five days during hospitalization, could improve clinical outcomes in patients with acute decompensated heart failure. The emerging data of the benefit of SGLT2 inhibitors in heart failure has been remarkable – first, in preventing heart failure hospitalizations in patients with diabetes, then in patients with heart failure and reduced ejection fraction, and, most recently, in the setting of heart failure with preserved ejection fraction. Could SGLT2 inhibitors also work in patients with decompensated heart failure, a population at very high risk of adverse events yet one in which there has been little progress made in improving outcomes? A prior trial (SOLOIST-WHF) of a combined SGLT1 and SGLT2 inhibitor (sotagliflozin) suggested benefit of that compound, but that trial was stopped prematurely, and the compound was started on the day of discharge or afterward.

In EMPULSE, 530 participants were randomized to empagliflozin 10 mg or placebo while admitted to the hospital with decompensated heart failure, including an elevated natriuretic peptide level, and followed for 90 days. Participants could have HFrEF or HFpEF and either have diabetes or not have diabetes. Participants had to have a systolic blood pressure ≥ 100 mm Hg and no IV inotropic therapy within 24 hours, among other exclusions. The primary endpoint was an interesting composite based on the “win ratio,” a hierarchical score that first assessed mortality and then heart failure events and finally change in the KCCQ Total Symptom score. The study met its primary endpoint with benefit occurring in 53.9% of those randomized to empagliflozin and only 39.7% in the placebo arm (p = 0.005). When assessing the components of the win ratio, both mortality (4.2% vs. 8.3%) and heart failure events (10.6% vs. 14.7%) were reduced numerically by empagliflozin. Subgroup analysis showed comparable benefit regardless of diabetic status and whether participants had new-onset or acute-on-chronic heart failure.

EMPULSE is an important trial. While we await its final publication at the time this article is being written, the data as presented strongly support initiating SGLT2 inhibition during hospitalization for acute decompensated heart failure. Such an approach would be a change in the current standard of care for this large and ill population. Further, given the benefit in those with new-onset heart failure, these data suggest that SGLT2i should be incorporated upfront, rather than sequentially following other components of quadruple therapy (e.g., ARNI, BBL, MRA), in that clinical setting. That, too, would represent a change in practice for many clinicians.

Email: mark.drazner@utsouthwestern.edu

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