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Randomized Controlled Trial
. 2023 Jul;25(7):970-977.
doi: 10.1002/ejhf.2861. Epub 2023 May 8.

Empagliflozin in heart failure with preserved ejection fraction with and without atrial fibrillation

Gerasimos Filippatos  1 , Dimitrios Farmakis  2 , Javed Butler  3   4 , Faiez Zannad  5 , João Pedro Ferreira  5   6 , Anne Pernille Ofstad  7   8 , Tomoko Iwata  9 , Martina Brueckmann  10   11 , Stuart J Pocock  12 , Milton Packer  13   14 , Stefan D Anker  15 ; EMPEROR-Preserved Trial Committees and Investigators
Affiliations
Free article
Randomized Controlled Trial

Empagliflozin in heart failure with preserved ejection fraction with and without atrial fibrillation

Gerasimos Filippatos et al. Eur J Heart Fail. 2023 Jul.
Free article

Abstract

Aims: Atrial fibrillation/flutter (AF) is common in heart failure (HF) with preserved left ventricular ejection fraction (LVEF) and associated with worse outcomes. Empagliflozin reduces cardiovascular death or HF hospitalizations and slows estimated glomerular filtration rate (eGFR) decline in patients with HF and LVEF >40%. We aimed to assess the efficacy and safety of empagliflozin in improving outcomes in patients with HF and LVEF >40% with and without AF.

Methods and results: In this pre-defined secondary analysis of EMPEROR-Preserved, we compared the effects of empagliflozin versus placebo on the primary and secondary endpoints and safety outcomes, stratified by baseline AF, defined as AF reported in any electrocardiogram before empagliflozin initiation or in medical history. Among 5988 patients randomized, 3135 (52%) had baseline AF; these patients were older, with worse functional class, more previous HF hospitalizations and higher natriuretic peptides compared to those without AF (all p < 0.001). After a median of 26 months, empagliflozin reduced cardiovascular death or HF hospitalization compared to placebo to a similar extent in patients with and without AF (hazard ratio [HR] 0.78 [95% confidence interval 0.66-0.93] vs. 0.78 [0.64-0.95], interaction p = 0.96). Empagliflozin also reduced total HF hospitalizations (HR 0.73 [0.57-0.94] vs. 0.72 [0.54-0.95], interaction p = 0.94) and annual eGFR decline (difference = 1.368 vs. 1.372 ml/min/1.73 m2 /year, interaction p = 0.99) consistently in patients with and without AF. There was no increase in serious adverse events with empagliflozin versus placebo in patients with and without AF.

Conclusions: In patients with HF and ejection fraction >40%, empagliflozin reduced the risk of serious HF events and slowed the eGFR decline regardless of baseline AF.

Keywords: Atrial fibrillation; Atrial flutter; Empagliflozin; Heart failure with preserved ejection fraction; Prognosis; Sodium-glucose cotransporter 2 inhibitor.

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References

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