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 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.
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.
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.
Effects of Empagliflozin on Markers of Liver Steatosis and Fibrosis and Their Relationship to Cardiorenal Outcomes
Diabetes Obes Metab 2022; doi:10.1111/dom.14670
In this study of adults with T2D and established CV disease, the proportion of patients at high steatosis risk decreased slightly in patients treated with empagliflozin compared with patients treated with placebo. Fibrosis risk was not reduced.
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.
Effects of Canagliflozin Versus Finerenone on Cardiorenal Outcomes: Exploratory Post-Hoc Analyses From FIDELIO-DKD Compared to Reported CREDENCE Results
Nephrol Dial Transplant 2021;gfab336 doi: 10.1093/ndt/gfab366
Finerenone and canagliflozin reduce cardiorenal risk in patients who are albuminuric. This exploratory post-hoc analyses by Agarwal et al. investigated how differences in trial design influenced observed treatment effects in the FIDELIO-DKD and CREDENCE studies.
N Engl J Med 2020;383:1413–24 DOI 10.1056/NEJMoa2022190
Empagliflozin demonstrated a reduction in CV death, HF hospitalisation, rate of eGFR decline and risk of serious renal outcomes in patients with chronic HF and reduced ejection fraction in the EMPEROR-reduced study.