Current perspectives of the use of Sodium Glucose Transport-2 Inhibitors for patients with heart failure and chronic kidney disease

2021 ◽  
Vol Publish Ahead of Print ◽  
Author(s):  
Etty Vider ◽  
Ravit Sapir ◽  
Eli Mosseri ◽  
Elizabeth Gavioli
Author(s):  
Aaron M. Hein ◽  
Julia J. Scialla ◽  
Jie-Lena Sun ◽  
Stephen J. Greene ◽  
Linda K. Shaw ◽  
...  

2018 ◽  
Vol 12 (3) ◽  
pp. 154-160
Author(s):  
Yohei Ono ◽  
Hiroto Takamatsu ◽  
Masahiro Inoue ◽  
Yukio Mabuchi ◽  
Tetsuya Ueda ◽  
...  

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Edouard L Fu ◽  
Alicia Uijl ◽  
Friedo W Dekker ◽  
Lars H Lund ◽  
Gianluigi Savarese ◽  
...  

Abstract Background and Aims Beta-blockers reduce mortality and morbidity in patients with heart failure (HF) with reduced ejection fraction (HFrEF). However, patients with advanced chronic kidney disease (CKD) were underrepresented in landmark trials. We evaluated if beta-blockers are associated with improved survival in patients with HFrEF and advanced CKD. Method We identified 3906 persons with an ejection fraction <40% and advanced CKD (eGFR <30 mL/min/1.73m2) enrolled in the Swedish Heart Failure Registry during 2001-2016. The associations between beta-blocker use, 5-year all-cause mortality, and the composite of time to cardiovascular (CV) mortality/first HF hospitalization were assessed by multivariable Cox regression. Analyses were adjusted for 36 variables, including demographics, laboratory measures, comorbidities, medication use, medical procedures, and socioeconomic status. To assess consistency, the same analyses were performed in a positive control cohort of 12,673 patients with moderate CKD (eGFR <60-30 mL/min/1.73m2). Results The majority (89%) of individuals with HFrEF and advanced CKD received treatment with beta-blockers. Median (IQR) age was 81 (74-86) years, 36% were women and median eGFR was 26 (20-28) mL/min/173m2. During 5 years of follow-up, 2086 (53.4%) individuals had a subsequent HF hospitalization, and 2954 (75.6%) individuals died, of which 2089 (70.1%) due to cardiovascular causes. Beta-blocker use was associated with a significant reduction in 5-year all-cause mortality [adjusted hazard ratio (HR) 0.86; 95% confidence interval (CI) 0.76-0.96)] and CV mortality/HF hospitalization (HR 0.87; 95% CI 0.77-0.98). The magnitude of the associations between beta-blocker use and outcomes was similar to that observed for HFrEF patients with mild/moderate CKD, with adjusted HRs for all-cause mortality and CV mortality/HF hospitalization of 0.85 (95% CI 0.78-0.91) and 0.88 (95% CI 0.82-0.96), respectively. Conclusion Despite lack of trial evidence, the use of beta-blockers in patients with HFrEF and advanced CKD was high in routine Swedish care, and was independently associated with reduced mortality to the same degree as HFrEF with moderate CKD.


2017 ◽  
Vol 234 (1) ◽  
pp. T125-T140 ◽  
Author(s):  
Peter Kolkhof ◽  
Lars Bärfacker

The cDNA of the mineralocorticoid receptor (MR) was cloned 30 years ago, in 1987. At that time, spirolactone, the first generation of synthetic steroid-based MR antagonists (MRAs), which was identified in preclinical in vivo models, had already been in clinical use for 30 years. Subsequent decades of research and development by Searle & Co., Ciba-Geigy, Roussel Uclaf and Schering AG toward identifying a second generation of much more specific steroidal MRAs were all based on the initial 17-spirolactone construct. The salient example is eplerenone, first described in 1987, coincidentally with the cloning of MR cDNA. Its launch on the market in 2003 paralleled intensive drug discovery programs for a new generation of non-steroidal MRAs. Now, 30 years after the cDNA cloning of MR and 60 years of clinical use of steroidal MRAs, novel non-steroidal MRAs such as apararenone, esaxerenone and finerenone are in late-stage clinical trials in patients with heart failure, chronic kidney disease (CKD), hypertension and liver disease. Finerenone has already been studied in over 2000 patients with heart failure plus chronic kidney disease and/or diabetes, and in patients with diabetic kidney disease, in five phase II clinical trials. Here, we reflect on the history of the various generations of MRAs and review characteristics of the most important steroidal and non-steroidal MRAs.


2011 ◽  
Vol 161 (1) ◽  
pp. 204-209.e1 ◽  
Author(s):  
Alawi A. Alsheikh-Ali ◽  
Thomas A. Trikalinos ◽  
Robin Ruthazer ◽  
Norma Terrin ◽  
John B. Wong ◽  
...  

2018 ◽  
Vol 5 (2) ◽  
pp. 319-326 ◽  
Author(s):  
Line Melgaard ◽  
Thure Filskov Overvad ◽  
Flemming Skjøth ◽  
Jeppe Hagstrup Christensen ◽  
Torben Bjerregaard Larsen ◽  
...  

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