Results of the phase 3 EMPEROR-Reduced trial indicate the SGLT2 inhibitor empagliflozin was effective for patients with HFrEF regardless of whether the patients had diabetes or not.
Empagliflozin (Jardiance) is effective for reducing risk of worsening heart failure regardless of whether or not a patient has diabetes, according to results of the phase 3 EMPEROR-Reduced trial.
Presented at the European Society of Cardiology (ESC) Congress 2020, results of the trial indicate empagliflozin was effective for reducing a composite of cardiovascular death or heart failure hospitalization regardless of diabetes status in a cohort of more than 3700 patients.
“We think EMPEROR-Reduced will have major implications for clinical practice,” said Milton Packer, MD, of Baylor University Medical Centre in Dallas, Texas, during a press conference. “When considered together with DAPA-HF the concordant results from these are actually remarkable. The SGLT2 inhibitors have clinically important benefits, they’re given once-daily, they require no dose-adjustment, and they’re very well-tolerated.”
One year after the paradigm-altering results of the DAPA-HF trial redefined the use SGLT2 inhibitors at ESC 2019, EMPEROR-Reduced demonstrates the effectiveness and safety of empagliflozin in patients with a more advanced state of heart failure with reduced ejection fraction (HFrEF). Designed as a randomized, double-blind, parallel-group, placebo-controlled, event-driven trial, EMPEROR-Reduced enrolled 3730 patients with the aim of evaluating the efficacy and safety profile of empagliflozin in patients with NYHA class II, III, or IV heart failure and an ejection fraction of 40% or less.
Initially, 7220 patients were screened for eligibility, which allows investigators to identify a cohort of 3730 to undergo randomization to 10 mg empagliflozin or placebo therapy. In total, 1863 patients were randomized to empagliflozin and 1867 were randomized to placebo. The primary outcome of the analysis was a composite of cardiovascular death or hospitalization for worsening heart failure.
In addition to the aforementioned criteria, patients were required to be at least 18 years of age, be receiving appropriate background therapies for heart failure, and to have a history of hospitalization for heart failure within the previous 12 months or a particularly NT-proBNP level, which was defined as a level of at least 1000 pg per milliliter in those with an ejection fraction of 31-35% or at least 2500 pg per milliliter in those with an ejection fraction of 36-40%.
During a follow-up period lasting a median of 16 months, a primary outcome event occurred in 19.4% (n=361) of patients in the empagliflozin group and 24.7% (n=462) of patients in the placebo group (HR, 0.75; 95% CI, 0.65-0.86; P <.001). Investigators noted results indicated the benefit of empagliflozin was consistent regardless of whether a patient had diabetes (HR, 0.72; 95% CI, 0.60-0.87) or did not have diabetes (HR, 0.78; 95% CI, 0.64-0.93).
Additionally, results indicated the number of total hospitalizations for heart failure was lower among patients receiving empagliflozin than those receiving placebo therapy (HR, 0.70; 95% CI, 0.58-0.85; P <.001). Results also suggested annual rate of decline in eGFR was lower with empagliflozin use than placebo (-0.55 vs -2.28 ml per minute per 1.73 m2 of body-surface area per year; P <.001) and patients treated with empagliflozin were at a lower risk of serious renal outcomes.
In regard to the safety of empagliflozin, investigators ported adverse renal outcomes occurred in 30 patients receiving empagliflozin compared to 58 patients in the placebo group (HR, 0.50; 95% CI, 0.32-0.77; P <.01). However, investigators pointed out an increase in uncomplicated genitourinary tract infections among patients receiving empagliflozin (1.3% vs 0.4%), but also noted frequency of hypotension, volume depletion, and hypoglycemia were similar between the groups.
“Empagliflozin reduced the risk of serious heart failure events by 30% and decreased the risk of serious adverse renal outcomes by 50%. This trial extends the benefits of SGLT2 inhibitors to higher-risk patients and shows a meaningful benefit on renal outcomes in patients with heart failure for the first time,” added Packer in a statement from the ESC.
This study, “Cardiovascular and Renal Outcomes with Empagliflozin in Heart Failure,” was presented at ESC Congress 2020 and simultaneously published in the New England Journal of Medicine.