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.

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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.

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Effects of Canagliflozin Versus Finerenone on Cardiorenal Outcomes: Exploratory Post Hoc Analyses From FIDELIO-DKD Compared to Reported CREDENCE Results

Nephrol Dial Transplant 2022;37:1261-9 doi.org/10.1093/ndt/gfab336

This analysis highlights the pitfalls of direct comparisons between trials, since when key differences in design are considered, FIDELIO-DKD and CREDENCE demonstrate similar cardiorenal benefits. The authors conclude that both canagliflozin and finerenone are similarly effective in reducing the risk of cardiorenal outcomes.

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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.

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Efficacy of Subcutaneous Semaglutide Compared to Placebo For Weight Loss in Obese, Non-diabetic Adults: A Systematic Review & Meta-Analysis

Int J Clin Pharm 2022; online ahead of print DOI: 10.1007/s11096-022-01428-1

This systematic review and meta-analysis validates the clinical efficacy of semaglutide for the treatment of obesity in adults without T2D. There is substantial evidence for clinicians to consider modification to their management obese population.

Research of the effect of semaglutide on weight loss has largely focused on T2D, and no meta-analyses in non-diabetic individuals have been conducted to date.

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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).

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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.

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Cardiovascular Outcomes in Patients Initiating First-Line Treatment of Type 2 Diabetes With Sodium–Glucose Cotransporter-2 Inhibitors Versus Metformin: A Cohort Study

Ann Intern Med 2022; doi:10.7326/M21-4012

This cohort study found that those initiating a SGLT2i as their first-line treatment for T2D showed a similar risk for a composite outcome of MI, stroke, and mortality – and lower risk for a composite of hospitalisation for heart failure (HHF) and mortality. Compared with those receiving metformin as their first-line treatment, the SGLT2i safety profile was similar, except for an increased risk of genital infections.

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Dose–Exposure–Response Analysis of the Nonsteroidal Mineralocorticoid Receptor Antagonist Finerenone on UACR and eGFR: An Analysis from FIDELIO‑DKD

Clin Pharmacokinet 2022; Ahead of print doi: 10.1007/s40262-022-01124-3

The results of this model-based analysis quantified the dose–exposure–response relationship for urine albumin-to-creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR). Overall, the relationship between finerenone exposure and UACR and eGFR effects was not modified by sodium-glucose co-transporter-2 inhibitor (SGLT2i) use and demonstrated independent and additive effects.

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