Publications
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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.
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Empagliflozin and Incidence of Events Consistent With Acute Kidney Injury: Pooled Safety Analysis in More Than 15,000 Individuals
Diabetes Obes Metab 2022;24:1390-3 doi: 10.1111/dom.14694
In this pooled analysis of patients from the global empagliflozin trial programme, the risk of acute kidney injury (AKI) and acute kidney disease (AKD) with empagliflozin was comparable with placebo. This comprehensive analysis indicates that empagliflozin is not associated with an increased risk of acute kidney failure compared with placebo treatment.
Design of the COmbinatioN effect of FInerenone anD EmpaglifloziN in participants with chronic kidney disease and type 2 diabetes using an UACR Endpoint study (CONFIDENCE)
Nephrol Dial Transplant 2022 Jun 14;gfac198. Online ahead of print. doi: 10.1093/ndt/gfac198.
CONFIDENCE is a new trial currently recruiting. The aim is to demonstrate that 6 months’ dual therapy with finerenone and empagliflozin is superior for reducing albuminuria versus either agent alone.
Despite available interventions, people with T2D remain at risk of chronic kidney disease, which puts them at further risk of kidney failure, CV morbidity, and all-cause mortality. There is therefore a need to slow or attenuate the progression of chronic kidney disease (CKD) and reduce CV morbidity and mortality in this population.
Finerenone and sodium-glucose cotransporter-2 inhibitors (SGLT2i) can both reduce kidney and CV risks, acting via both shared and distinct pathophysiological pathways. Results from post hoc subgroup analyses and a preclinical model suggest dual therapy may provide additive renoprotective effects than using either class alone.
Empagliflozin and Serum Potassium in Heart Failure: An Analysis From Emperor-Pooled
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.
Randomized Controlled Trial of the Hemodynamic Effects of Empagliflozin in Patients With Type 2 Diabetes at High Cardiovascular Risk: The SIMPLE Trial
Diabetes 2022;71:812–20 doi.org/10.2337/db21-0721
In this analysis of data from the SIMPLE trial, empagliflozin did not reduce left heart filling pressure more than placebo at submaximal exercise in patients with T2D at high CV risk. However, it was observed that empagliflozin reduced pulmonary capillary wedge pressure (PCWP) at a magnitude of clinical significance in patients at rest. The findings suggest cardiac benefits beyond the diuretic effect of sodium-glucose co-transporter-2 inhibitor (SGLT2i) treatment and could explain a significant part of the CV benefits observed in clinical trials.
Effects of Empagliflozin on Symptoms, Physical Limitations and Quality of Life in Patients Hospitalized for Acute Heart Failure – Results From the EMPULSE Trial
Circulation 2022; online ahead of print doi:10.1161/CIRCULATIONAHA.122.059725
This post hoc and prespecified analysis of the EMPULSE trial found that initiation of empagliflozin in patients hospitalised for acute heart failure (AHF) produced clinical benefit regardless of the degree of symptomatic impairment at baseline. Empagliflozin also improved symptoms, physical limitations, and quality of life – with benefits seen as early as 15 days and maintained through 90 days.
Empagliflozin and Incidence of Events Consistent With Acute Kidney Injury: Pooled Safety Analysis in >15,000 Individuals
Diabetes Obes Metab 2022;doi:10.1111/dom.14694 Ahead of print
This comprehensive analysis indicates that empagliflozin is not associated with increased risk of acute kidney injury or acute kidney failure compared with placebo treatment.
The SGLT2 Inhibitor Empagliflozin in Patients Hospitalized For Acute Heart Failure: A Multinational Randomized Trial
Nature Med 2022;28:568–74 doi: 10.1038/s41591-021-01659-1
Empagliflozin is well tolerated in patients hospitalised for acute heart failure, resulting in significant clinical benefit 90 days after treatment initiation.