At the 71st annual American College of Cardiology (ACC) meeting, results were presented for the EMPULSE trial demonstrating that Boehringer Ingelheim’s (BI) sodium-glucose co-transporter-2 inhibitor (SGLT-2I) empagliflozin (Jardiance) was beneficial at reducing adverse events among acute decompensated heart failure (ADHF) patients. The trial aimed to evaluate empagliflozin compared to placebo in patients with ADHF, with empagliflozin having previously demonstrated a reduction in risk of cardiovascular death or heart failure (HF) hospitalisation among patients with chronic heart failure (CHF).
Empagliflozin was originally approved to treat patients with type 2 diabetes (T2D) and, in addition to other SGLT-2Is, has demonstrated efficacy in treating both CHF and systolic HF. The drug is currently in Phase III trials for chronic kidney disease. With the increasing metabolic complexity that cardiovascular and T2D patients present, the additional clinical benefits that empagliflozin offers these patients will strengthen its position in an increasingly competitive SGLT-2I class. Key opinion leaders (KOLs) interviewed by GlobalData have expressed positive sentiments regarding the expanding clinical benefits of the SGLT-2I class as it provides them with a drug that addresses multiple comorbidities, with good efficacy, in a single dose.
Patients with ADHF were randomised into either the treatment arm of empagliflozin 10mg daily (n=265) or the placebo arm (n=265). There were a total number of 530 enrollees with a 90-day duration period between follow-ups and a mean patient age of 71 years; 33% of patients were female, while 47% of patients enrolled had diabetes. Specific inclusion criteria for the trial included patients admitted to hospital with ADHF regardless of ejection fraction or diabetes status, a systolic blood pressure of ≥100mmHg and no symptoms of hypotension within six hours of admission, NT-proBNP ≥1,600pg/mL or BNP ≥400pg/mL during hospitalisation or within 72 hours prior to admission, and a median left ventricular ejection fraction (LVEF) of 31%.
A stratified ratio was determined, which was defined as a composite of death, the number of HF events, time to first HF event, and a change in the Kansas City Cardiomyopathy Questionnaire-Total Symptom Score (KCCQ-TSS) from baseline to 90 days. Clinical benefit occurred at a rate of 53.9% in the empagliflozin group compared with 39.7% in the placebo group (p=0.0054). Secondary outcomes were as follows:
- Death: 4.2% in the empagliflozin group vs 8.3% in the placebo group
- HF event: 10.6% in the empagliflozin group vs 14.7% in the placebo group
- Change in KCCQ-TSS: 4.5 points for the empagliflozin group vs the placebo group (p=0.035)
- Acute renal failure: 7.7% in the treatment arm compared to 12.1% in the placebo group
Empagliflozin was able to demonstrate, compared with placebo, significant clinical benefit at 90 days in patients with ADHF. The EMPULSE trial enrolled participants regardless of ejection fraction or their diabetes status, and there was no evidence for treatment interaction based on either of these two variables. The benefit of empagliflozin was independent of any symptomatic impairment at baseline and empagliflozin versus placebo was associated with fewer deaths, improvement in quality of life, and a significant reduction in body weight, with no significant safety issues observed with empagliflozin.
GlobalData predicts that the data from the EMPULSE trial will strengthen BI’s position in an increasingly competitive SGLT-2I market, in both HF and T2D. Empagliflozin will likely achieve significant uptake from physicians and be a direct competitor to dapagliflozin (Farxiga), which was the first SGLT-2I approved for HF, and erode some of Farxiga’s market share.