Cardiac and Kidney Benefits of Empagliflozin in Heart Failure Across the Spectrum of Kidney Function: Insights From the EMPEROR-Preserved Trial
European Journal of Heart Failure 2023 DOI 10.1002/ejhf.2857
In the EMPEROR-Preserved trial, empagliflozin was found to improve the clinical outcomes of patients with heart failure and preserved ejection fraction (HFpEF). This pre-specified analysis sought to explore the effect of empagliflozin on cardiovascular (CV) and kidney outcomes across different levels of kidney function.
Efficacy of Empagliflozin in Heart Failure with Preserved versus Mid-range Ejection Fraction: a Pre-specified Analysis of EMPEROR-Preserved
Nat Med. 2022;28:2512–2520 DOI: 10.1038/s41591-022-02041-5
Results from EMPEROR-Preserved demonstrated that empagliflozin improved CV death and HF hospitalisation – the primary outcome – in patients with HF and LVEF >40%. This pre-specified analysis of EMPEROR-Preserved aimed to evaluate the effect of empagliflozin in patients with HFpEF (LVEF ≥50%) compared with patients who had HFmrEF (LVEF 41–49%).
Empagliflozin, Irrespective of Blood Pressure, Improves Outcomes in Heart Failure with Preserved Ejection Fraction: the EMPEROR-Preserved Trial
Eur Heart J. 2022; online ahead of print DOI: 10.1093/eurheartj/ehac693
Results from EMPEROR-Preserved demonstrated that empagliflozin improved CV and renal outcomes in patients with HFpEF, but its efficacy and safety with baseline SBP is not well established.
Circulation. 2022; online ahead of print DOI: 10.1161/CIRCULATIONAHA.122.062644
While analyses from DAPA-HF and EMPEROR-Reduced demonstrated a consistent benefit of SGLT2i in Black patients, data were limited to HFrEF and included a small number of Black patients. In the current analysis, the efficacy and safety of empagliflozin according to Black vs White race in the Americas was assessed across the spectrum of EF in EMPEROR-Pooled, a combined dataset from both EMPEROR trials.
Association of Empagliflozin Treatment With Albuminuria Levels in Patients With Heart Failure: A Secondary Analysis of EMPEROR-Pooled
JAMA Cardiol. 2022; online ahead of print DOI: 10.1001/jamacardio.2022.2924
In a post-hoc analysis of EMPEROR-Pooled, empagliflozin was associated with a reduction in the primary outcome irrespective of albuminuria levels at baseline compared with placebo, and there was reduced progression to macroalbuminuria and reversion of macroalbuminuria.
Uric Acid and Sodium-Glucose Cotransporter-2 Inhibition With Empagliflozin in Heart Failure With Reduced Ejection Fraction: The EMPEROR-Reduced Trial
Eur Heart J 2022; online ahead of print doi.org/10.1093/eurheartj/ehac320
Hyperuricaemia is common in heart failure (HF) and is an independent predictor of advanced disease severity and increased mortality. This analysis from EMPEROR-Reduced showed that empagliflozin induced a rapid and sustained reduction of both serum uric acid (SUA) and of clinical events related to hyperuricaemia.
Empagliflozin Improves Outcomes in Patients With Heart Failure and Preserved Ejection Fraction Irrespective of Age
J Am Coll Cardiol 2022;80(1):1-18 doi: 10.1016/j.jacc.2022.04.040
Sodium-glucose cotransporter-2 inhibitors (SGLT2i) reduce cardiovascular death and hospitalisation for heart failure (HHF) in patients with HFpEF, and are recommended in recent guidelines for heart failure with reduced ejection fraction (HFrEF), supported by Class IA evidence. Typically, HFpEF patients are older than HFrEF, and have a higher mortality risk associated with older age, while the risk for cardiovascular death is lower than in HFrEF. Until now, the treatment effects and safety of SGLT2i in relation to age have not been studied. This prespecified analysis of the EMPEROR-Preserved trial examined the interplay of age and empagliflozin treatment effects.
For patients on placebo, the incidence of primary outcomes and cardiovascular death increased with age. In contrast, empagliflozin reduced the primary outcome, first HHF, and first and recurrent HHF across all age groups. Empagliflozin also improved health-related quality of life, and attenuated the decline of eGFR without age interaction. Additionally, there were no clinically relevant differences in AEs between empagliflozin and placebo across the age groups, and elderly patients tolerated the treatment well.
Empagliflozin for Heart Failure With Preserved Left Ventricular Ejection Fraction With and Without Diabetes
Circulation 2022; online ahead of print
In patients enrolled in EMPEROR-Preserved, empagliflozin significantly reduced the risk of heart failure (HF) outcomes irrespective of diabetes status.
Eur Heart J 2022; online ahead of print DOI: 10.1093/eurheartj/ehac306
In this pooled analysis, empagliflozin reduced the incidence of hyperkalaemia without significant increase in hypokalaemia.
Potassium is essential for normal cellular function, but severe potassium abnormalities can lead to cardiac arrhythmias and death. Hyperkalaemia frequently leads to interruption and discontinuation of neurohormonal antagonists, which may worsen the prognosis for people with heart failure (HF).
Prognostic Implications of N-terminal Pro-B Type Natriuretic Peptide and High-Sensitivity Cardiac Troponin T in EMPEROR-Preserved
JACC Heart Fail 2022 doi:S2213-1779(22)00302-X
This planned analysis from EMPEROR-Preserved provides strong evidence for both N-terminal pro-B type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (hs-cTnT) as important disease markers and prognostic indicators in people with heart failure with preserved ejection fraction (HFpEF).
Evaluation and management of individuals with HFpEF can be challenging. NT-proBNP and hs-cTnT are biomarkers with well-established prognostic role across the range of ejection fraction in heart failure. As such, it is possible that patient baseline values could be used to identify those suitable for treatment. However, ambiguity has led to confusion about pharmacologic management, and the role of biomarkers.