Full Steam Ahead for SGLT2 Inhibitors

Volume 13, Issue 1

The SGLT2 inhibitors have been frequently highlighted in prior Talking Therapeutics columns. These impressive agents continue to accumulate data demonstrating marked benefits for patients with heart failure.

Last week, the FDA approved empagliflozin for patients with heart failure with preserved ejection fraction (HFpEF), which marked the first time that a drug was specifically indicated to reduce major adverse cardiac events in this patient population. On top of that exciting news, a new study was just published this week which identifies a new potential use for these agents.  

Point 1: SGLT2 Inhibitors Move Into the Acute Heart Failure Sphere 

Up until now, the bulk of experience with SGLT2 inhibitors has been in patients with chronic stable heart failure. This week, the EMPULSE trial was published in Nature Medicine, and evaluated the use of empaglifozin in 530 patients admitted to hospital with an acute heart failure exacerbation. 

Patients were randomized to receive either empaglifozin or placebo once they were clinically stable and were treated for up to 90 days. The primary outcome “was clinical benefit, defined as a hierarchical composite of death from any cause, number of heart failure events and time to first heart failure event, or a 5 point or greater difference in change from baseline in the Kansas City Cardiomyopathy Questionnaire Total Symptom Score at 90 days.”

Compared to those receiving placebo, more patients in the empagliflozin group met the primary outcome (stratified win ratio, 1.36; 95% confidence interval, 1.09-1.68; P = .0054), and the clinical benefit was seen regardless of the baseline ejection fraction. Importantly, no ketoacidosis occurred among patients receiving empagliflozin.

Researchers also found the following:

• Investigator-defined serious symptomatic hypotension occurred in 1.2% of the patients in the empagliflozin group and in 1.5% in the placebo group;
• acute renal failure occurred in 7.7% of patients in the empagliflozin group and in 12.1% of patients in the placebo group; and
• urinary tract infection occurred in 4.2% of the patients in the empagliflozin group and in 6.4% in the placebo group.  

Point 2: SGLT2 Inhibitors Should Be Used Across the Spectrum of Heart Failure 

These data represent a potential watershed moment in the case of acute heart failure, as many other therapies have not proven effective at improving cardiovascular outcomes in this clinical scenario. Given what is already known about the long-term benefits of SGLT2 inhibitors in patients with chronic heart failure, it now makes very good sense to initiate these agents during any admission for acute heart failure (regardless of ejection fraction), based on the EMPULSE trial.

Such a strategy would translate into improvements in key short- and long-term cardiovascular outcomes for patients across the spectrum of heart failure.