Empagliflozin may be beneficial in acute HF

Abstract

Adults treated with empagliflozin (Jardiance—Boehringer Ingelheim, Lilly) during hospitalization for an acute heart failure (HF) event had reduced all-cause mortality, fewer HF events, and improvement in HF–related symptoms compared with those given a placebo, according to results of the EMPULSE trial presented at the 2021 American Heart Association (AHA) Scientific Sessions. These data add to the broader information supporting the use of sodium-glucose cotransporter 2 (SGLT-2) inhibitors to improve CV events in those with HF, specifically when in the acute care setting. “Short-term clinical outcomes of patients hospitalized for acute HF are poor,” said lead study author Adriaan A. Voors, MD, PhD, professor of cardiology at the University Medical Center Groningen in the Netherlands. “EMPULSE shows adults hospitalized for acute HF were 36% more likely to experience a clinical benefit over 90 days if initiated on empagliflozin compared with [a] placebo following stabilization and prior to discharge.” Although the cardiovascular benefits of select SGLT-2 inhibitors in patients with and without type 2 diabetes—including improved outcomes in those with chronic HF—are well-established, physicians have been reluctant to use this class of drugs in the acute HF setting due to potential safety concerns. This is unfortunate because patients with acute HF are at an even higher risk of death and risk of hospital readmission for HF in the early months post-discharge. The results of the EMPULSE study support empagliflozin’s effects in improving outcomes in those with acute HF, but also the safe use of this agent in acute care setting. Patients treated with empagliflozin had no ketoacidosis or hypotension and only a slight drop in renal function, which disappeared after approximately 15 days. Several limitations with the data need to be considered, however. First, patients had to be “stable” before trial enrollment. Second, empagliflozin was added onto the standard management of acute HF and the information on the list of concurrent medications are not yet published and would be helpful to assess. Third, the trial is relatively small compared with other major cardiovascular outcome trials, so additional confirmatory analyses may be needed. Finally, cost is always a consideration when adding a new treatment onto a patient’s regimen, especially when they are already receiving numerous medications to manage their condition. The EMPULSE trial enrolled 530 patients hospitalized with a primary diagnosis of acute HF, defined as de novo or decompensated chronic HF, regardless of left ventricular ejection fraction or diabetes status. Patients with a mean age of 68 years were randomized to receive 10 mg of empagliflozin daily or placebo for 90 days. Treatment was initiated once patients were stabilized, which averaged approximately 3 days after admission. The primary outcome was a composite of the number of deaths, heart failure–related events, time to the first heart failure event, or an improved score of at least 5 points on the Kansas City Cardiomyopathy Questionnaire (KCCQ). Patients assigned to empagliflozin were 36% more likely to experience clinical benefit at 90 days compared with those in the placebo group. All-cause mortality was 4.2% in the empagliflozin group compared with 8.3% in the placebo group, and HF events were 10.6% in the empagliflozin group compared with 14.7% in the placebo group. Fewer serious HF events also occurred in the active treatment group (32.3% vs. 43.6%). Additionally, those who received empagliflozin had a 4.5-point increase in the KCCQ total symptom score compared with the placebo group (mean change from baseline 36.9 vs. 31.6). Empagliflozin was well-tolerated in patients with acute HF according to the study, with fewer serious adverse events in the empagliflozin group compared with the placebo group.