EMPEROR’s New Groove? Empagliflozin Provides Long-Awaited Treatment for HFpEF

Empagliflozin, a sodium glucose co-transporter 2 inhibitor (SGLT2i), significantly reduced the composite endpoint of heart failure (HF) hospitalization and cardiovascular death in patients with HF with preserved ejection fraction (HFpEF).

Presented at a Hot Line session at the European Society of Cardiology Congress 2021, empagliflozin has delivered a long-anticipated therapy for patients with HFpEF. Despite the armamentarium of beneficial medications for HF patients with reduced ejection fraction, HFpEF notoriously has limited treatment options. SGLT2i therapy was hypothesized to be the breakthrough for this population following reductions in HF hospitalization and cardiovascular death in patients with diabetes and HF across the full spectrum of ejection fraction (EF).¹

💥My top 10 learning points from the #ESCCongress 2021💥

A thread for cardiologists/general physicians

1) There is a treatment for HFpEF!

Empagliflozin significantly ⬇️composite of HF hospitalisation & CV death by 21%

Evidence: EMPEROR-Preserved https://t.co/VuBcsxoimo

1/n pic.twitter.com/NBpglmrAOK

— Sarah Hudson (@sarahhudsonuk) August 30, 2021

The EMPEROR-Preserved trial, simultaneously published in the New England Journal of Medicine, randomized patients with symptomatic HFpEF (EF >40%) to empagliflozin 10 mg daily or placebo.² Both patients with and without diabetes were included, but all had to have an elevated N-terminal pro-B-type natriuretic peptide (>300 pg/mL or >900 pg/mL if concurrent atrial fibrillation) and evidence of either structural heart disease or prior hospitalization for heart failure. The primary outcome was combined cardiovascular death or HF hospitalization.

A total of 5,988 participants (mean age 72 years, 45% women, mean EF 54%) were included in the trial. Over 26 months of median follow-up 415 of 2,997 participants (13.8%) had the primary outcome occur in the empagliflozin group, compared to 511 of 2,991 (17.1%) in the placebo group (HR=0.79; 95% CI 0.69 to 0.90, P=0.0003). The effect was carried by significantly reduced first, and recurrent, HF hospitalizations (HR=0.73; 95% CI 0.61 to 0,88, P<0.001).

My take on #EMPERORpreserved
✅first trial with big and convincing ⬇️CV💀+HF🏥 in #HFpEF
✅driven by reduction in HF🏥 (as expected)
✅consistent across LVEF spectrum (not as big in LVEF>60 but still in right direction!)
✅safe and well tolerated#ESCCongress @escardio pic.twitter.com/uU4WAieXbH

— Andreas Gevaert (@AndreasGevaert) August 27, 2021

Similar effects in the primary outcome were seen across pre-specified sub-groups of EF, up to 60%, and regardless of underlying diabetes status. The attenuation of benefit in the sub-group with EF >60% or lack of significant reduction in cardiovascular death stopped this trial from fully addressing the treatment gap in HFpEF.

Dr. Milton Packer, a principal investigator of the study, noted “we are pleased to have the first trial in patients with HFpEF that shows an unequivocally positive and clinically important result. We are looking forward to many secondary papers that will provide detailed information about what we have found, and what it means for patients.”

To date, HFpEF treatment has revolved around biologic plausibility, sub-analyses of neutral trials, and management of co-morbidities. Therefore, despite the lack of mortality benefit, a positive randomized-controlled trial indicating significant improvement in morbidity for this population is welcome. Following the results of EMPEROR-Preserved, the medical community seems to have found a new groove for HFpEF therapy.

Dr. Stefan Anker presents the results of the EMPORER-Preserved trial – in patients with HF and an ejection fraction >40%, empagliflozin reduced the composite of CV death and hospitalization for HF by 21%. Full slide deck: https://t.co/2fIzjfS5Cf pic.twitter.com/46XkUyhqfl

— C. Michael Gibson MD (@CMichaelGibson) August 27, 2021

References

1. Bhatt DL, Szarek M, Steg PG et al. Sotagliflozin in Patients with Diabetes and Recent Worsening Heart Failure. N Engl J Med. 2021;384:117-128.
2. Anker SD, Butler J, Filippatos G et al. Empagliflozin in Heart Failure with a Preserved Ejection Fraction. N Engl J Med. 2021.

One week after the #ESCCongress2021, I'd like to share w/ you my top #HotTopics summarised by graphics (credits to @escardio) and links attached

1⃣ #EMPERORPRESERVED:
🔸First trial to reach 1ºEP (HF+CV death) in #HFpEF‼️
📁https://t.co/Il3IfRmZRy#CardioEd #CardioTwitter pic.twitter.com/yBLFo3v4jp

— Diego Segura-Rodríguez (@SeguraCardio) September 4, 2021