Finerenone in Patients With Chronic Kidney Disease and Type 2 Diabetes by Sodium–Glucose Cotransporter 2 Inhibitor Treatment: The FIDELITY Analysis
Diabetes Care 2022; online ahead of print doi: 10.2337/dc22-0294
In the FIDELITY analysis, finerenone reduced the risk of cardiovascular and kidney outcomes compared with placebo. Concomitant treatment with a sodium-glucose cotransporter-2 inhibitor (SGLT2i) did not modify the observed benefits.
FIDELITY pooled populations from the FIDELIO-DKD and FIGARO-DKD studies in order to examine the effect of finerenone and interaction with SGLT2i use on prespecified outcomes in patients with chronic kidney disease (CKD) and type 2 diabetes (T2D). In both trial, use of SGLT2i was permitted at baseline, as was initiation of SGLT2i at any time during the trial.
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.
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.
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.
Early Benefit With Empagliflozin in Heart Failure With Preserved Ejection Fraction: Insights From the EMPEROR-Preserved Trial
Eur J Heart Fail 2022;24(2):245–8. doi:10.1002/ejhf.2420
Results reinforce sustained clinical, health status and quality of life benefits with empagliflozin in patients with HF‑pEF, and underscore the need for timely initiation of therapy.
Finerenone in Predominantly Advanced CKD and Type 2 Diabetes With or Without Sodium-Glucose Cotransporter-2 Inhibitor Therapy
Kidney Int Rep 2022;7:36–45 doi.org/10.1016/j.ekir.2021.10.008
Finerenone was associated with a 31% greater reduction in urine albumin:creatinine ratio (UACR) from baseline to Month 4 versus placebo. With similar reductions in UACR seen whether the patient was receiving SGLT2i at baseline or not.
Empagliflozin in the Treatment of Heart Failure With Reduced Ejection Fraction in Addition to Background Therapies and Therapeutic Combinations (EMPEROR-Reduced): A Post-hoc Analysis of a Randomised, Double-blind Trial
Lancet Diabetes Endocrinol 2022;10:35–45 doi.org/10.1016/S2213-8587(21)00292-8
The data from the trial suggests that empagliflozin may be considered as a foundational therapy in heart failure with reduced ejection fraction. This post-hoc analysis of EMPEROR-Reduced – a randomised, double-blind, parallel-group trial – by Verma et al. evaluated the efficacy and safety of empagliflozin in patients with heart failure with reduced ejection fraction and to baseline treatment.