Patients hospitalized with acute heart failure (HF) have a reduced risk of subsequent HF events or all-cause mortality if treated with once-daily empagliflozin while in hospital, according to results of the EMPULSE trial presented at HFSA 2022.
Participants were 530 adults hospitalized with acute HF (de novo or decompensated chronic HF) regardless of ejection fraction (EF) or diabetes status. To be included, patients needed to have systolic blood pressure (BP) levels
≥100 mg Hg, NT-proBNP levels ≥1,600 pg/mL or BNP ≥400 pg/mL within 72 hours of admission, no intravenous (IV) inotropic drugs in the prior 24 hours, and no hypotension symptoms, or increase in IV diuretic dose or vasodilators in the prior 6 hours. They were randomized (≥24 hours and
≤5 days post-admission) to receive empagliflozin 10 mg or placebo QD.
Over the 90-day follow-up period, 94 patients (mean age 70 years, 37 percent female) experienced a composite of HF events* or all-cause mortality. Compared with the 436 patients (mean age 68 years, 33 percent female) who did not experience the composite, those who did were less likely to have acute de novo HF (19 percent vs 36 percent) or be on neurohormonal blockade drugs (54 percent vs 73 percent) and more likely to have diabetes (57 percent vs 43 percent), and have higher EF (mean 38 percent vs 34 percent) and NT-proBNP (median 4,393 vs 2,992 pg/mL) and lower eGFR levels (mean 49 vs. 55 mL/min/1.73 m2).
The risk of HF events or all-cause mortality was significantly reduced among patients who received empagliflozin compared with placebo (14 percent vs 22 percent [events]; hazard ratio [HR]0.65, 95 percent confidence interval [CI], 0.43–0.99; p=0.042), with 15 patients needing to be treated to prevent one event over 90 days. [HFSA 2022, session: Late Breaking Clinical Trials 1]
“The beneficial effect of empagliflozin over placebo was consistent across subgroups, regardless of patient demographics or baseline BP,” presented Dr. Megan McLaughlin from the University of California, San Francisco, California, US. In addition, the results were consistent regardless of baseline EF (HRs, 0.61 and 0.73 for < and ≥median, respectively; pinteraction=0.68), diabetes status (HRs, 0.66 and 0.63 for with and without type 2 diabetes, respectively; pinteraction=0.92), and acute de novo vs decompensated chronic HF (HRs, 0.48 and 0.70, respectively; pinteraction=0.50).
Time to HF event did not significantly differ between patients assigned to empagliflozin and placebo (11 percent vs 15 percent; HR, 0.72, 95 percent CI, 0.44–1.17; p=0.183). Fewer deaths occurred in the empagliflozin than placebo group (n=11 vs 22 [4 percent vs 8 percent]), with a non-significant trend toward a reduced risk of all-cause mortality with empagliflozin vs placebo (HR, 0.52, 95 percent CI, 0.25–1.07; p=0.074).
Similarly, there were fewer cardiovascular (CV) deaths in the empagliflozin vs placebo group (n=8 vs 14 [3 percent vs 5 percent]), with a non-significant trend toward a reduced risk of CV mortality with empagliflozin vs placebo (HR, 0.59; p=0.227) and composite of time to HF event and CV mortality (13 percent vs 18 percent; HR, 0.69; p =0.102).
Likelihood of intensive care unit (ICU) admission was comparable between groups (nine patients in each group), as was duration of hospitalization (median 7 vs 8 days [empagliflozin vs placebo]; p=0.56) or ICU stay (median 4 vs 9 days; p=0.18), and initiation or escalation of treatment (p=0.97).
The trial had several limitations including the short follow-up period, low number of events, and potential exclusion of more frail patients with more severe disease, noted McLaughlin.
“[Nonetheless,] the administration of empagliflozin in patients stabilized during a hospitalization for acute HF decreased the risk of HF events or all-cause mortality with benefits apparent within 90 days, supporting early initiation of empagliflozin in the inpatient setting,” she concluded.