European Society of Cardiology

European Society of Cardiology

Source:

Anker SD, et al. Hot Line: EMPEROR-Preserved/EMPEROR-Pooled. Presented at: European Society of Cardiology Congress; Aug. 27-30, 2021 (virtual meeting).

Disclosures: The trial was funded by Boehringer Ingelheim and Eli Lilly. Anker reports receiving grants from Vifor; personal fees from Bayer, Boehringer Ingelheim, Cardiac Dimensions, Impulse Dynamics, Novartis, Servier, Thermo Fisher Scientific and Vifor; and grants and personal fees from Abbott Vascular outside the submitted work. Please see the study for the other authors’ relevant financial disclosures. Aguiar reports no relevant financial disclosures. Drazner reports receiving an institutional research grant from AstraZeneca.
August 27, 2021
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Empagliflozin becomes first agent to improve outcomes in HFpEF: EMPEROR-Preserved

Source:

Anker SD, et al. Hot Line: EMPEROR-Preserved/EMPEROR-Pooled. Presented at: European Society of Cardiology Congress; Aug. 27-30, 2021 (virtual meeting).

Disclosures: The trial was funded by Boehringer Ingelheim and Eli Lilly. Anker reports receiving grants from Vifor; personal fees from Bayer, Boehringer Ingelheim, Cardiac Dimensions, Impulse Dynamics, Novartis, Servier, Thermo Fisher Scientific and Vifor; and grants and personal fees from Abbott Vascular outside the submitted work. Please see the study for the other authors’ relevant financial disclosures. Aguiar reports no relevant financial disclosures. Drazner reports receiving an institutional research grant from AstraZeneca.
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Anticipated results of the EMPEROR-Preserved trial demonstrate that the SGLT2 inhibitor empagliflozin improved clinical outcomes in patients with HF with preserved ejection fraction — the first agent to be shown to do so.

The trial of empagliflozin (Jardiance, Boehringer Ingelheim/Eli Lilly) included patients with HFpEF with or without diabetes. As Healio previously reported, empagliflozin improved clinical outcomes in patients with HF and reduced ejection fraction with or without diabetes in the EMPEROR-Reduced trial.

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“These results represent the first trial to show unequivocal benefit of any drug on major heart failure outcomes in patients with heart failure and a preserved ejection fraction,” Stefan D. Anker, MD, PhD, heart failure cardiologist at Charité Berlin, Germany, said during a press conference at the European Society of Cardiology Congress.

EMPEROR-Preserved was simultaneously published in The New England Journal of Medicine.

EMPEROR-Preserved results

Stefan D. Anker

Anker and colleagues randomly assigned 5,988 patients (mean age, 72 years; 45% women; 49% with diabetes) with NYHA class II to IV HF and an EF above 40% to receive empagliflozin 10 mg daily or placebo. The primary outcome was CV death or hospitalization for HF.

During a median follow-up of 26.2 months, the primary outcome occurred in 13.8% of the empagliflozin group compared with 17.1% of the placebo group (HR = 0.79; 95% CI, 0.69-0.9; P < .0003; number needed to treat to prevent one event = 31), driven by HF hospitalization (HR = 0.71; 95% CI, 0.6-0.83). Anker said the results were consistent in patients with and without diabetes. He added that the results did not differ according to EF (41% to 49%, 50% to 59% or 60% or more), with a P value for trend of .21.

The first secondary outcome, total (first and recurrent) hospitalizations for HF, was lower in the empagliflozin group (HR = 0.73; 95% CI, 0.61-0.88; P < .0009), Anker said.

The second secondary outcome of slope of decline in glomerular filtration rate over time also favored empagliflozin (difference, 1.36 mL/min/1.73m2 per year; P < .0001), according to the results.

CV death was reduced by 9% in the empagliflozin group, but the reduction was not statistically significant (HR = 0.91; 95% CI, 0.76-1.09), Anker said. There was no difference between the groups in all-cause mortality (HR = 1; 95% CI, 0.87-1.15).

The empagliflozin group had higher rates of uncomplicated genital and urinary tract infections and hypotension than the placebo group, but there was no difference between the groups in amputation, ketoacidosis and hypoglycemia, according to Anker.

Challenges of HFpEF

Anker said the EMPEROR-Preserved trial’s success comes after years of failure to show statistically significant benefits in clinical outcomes in patients with HFpEF with other agents, including the CHARM-Preserved trial of candesartan, the PEP-CHF trial of perindopril, the I-PRESERVE trial of irbesartan, the TOPCAT trial of spironolactone and the PARAGON-HF trial of sacubitril/valsartan (Entresto, Novartis).

“Only today we can now say that for the first time [improvement in key clinical outcomes] is possible with empagliflozin in heart failure with preserved ejection fraction,” Anker said. “It was a clinically meaningful and important reduction.”

During a discussion at the press conference, Carlos Aguiar, MD, cardiology consultant and chair of the Advanced Heart Failure and Heart Transplantation Unit at Hospital Santa Cruz, Carnaxide, Portugal and chairperson of the ESC’s Communications Committee, said, “as a physician treating patients with heart failure, I can testify that this is something I feel will definitely be changing our practice, and quite quickly. We have been using this class of drugs for quite some time in the field of cardiovascular medicine in patients with diabetes, and we have been eager to find treatments for patients with heart failure and preserved ejection fraction that can reduce morbidity and even possibly mortality.”

Mark Drazner

In a related editorial in NEJM, Mark Drazner, MD, MSc, clinical chief of cardiology and James M. Wooten Chair in Cardiology at University of Texas Southwestern Medical Center, noted that “these data suggest that empagliflozin has less of a kidney-protective effect in patients with heart failure and a preserved ejection fraction than in patients with a reduced ejection fraction. ... On the basis of these findings, it seems likely that renal protection is not the main mechanism by which empagliflozin prevents hospitalization for heart failure.”

According to Drazner, the EMPEROR-Preserved trial represents “a major win against a medical condition that had previously proved formidable. Ultimately, the EMPEROR-Preserved trial should contribute to a change in clinical practice, given the paucity of therapeutic options available for patients with heart failure and a preserved ejection fraction.”

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