scholarly journals Combined SGLT ‐2 and ACE inhibition upregulates the renin‐angiotensin system in chronic kidney disease with type 2 diabetes: Results of a randomized, double‐blind, placebo‐controlled exploratory trial

2022 ◽  
Author(s):  
Marlies Antlanger ◽  
Oliver Domenig ◽  
Christopher C Kaltenecker ◽  
Johannes J Kovarik ◽  
Vincent Rathkolb ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Renin Angiotensin System ◽  
Ace Inhibition ◽  
Double Blind ◽  
Angiotensin System ◽  
Double Blind Placebo ◽  
Exploratory Trial

scholarly journals Finerenone and Cardiovascular Outcomes in Patients with Chronic Kidney Disease and Type 2 Diabetes

Circulation ◽  
2020 ◽  
Author(s):  
Gerasimos Filippatos ◽  
Stefan D. Anker ◽  
Rajiv Agarwal ◽  
Bertram Pitt ◽  
Luis M. Ruilope ◽  
...  
Keyword(s):  
Heart Failure ◽  
Type 2 Diabetes ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Renin Angiotensin System ◽  
Mineralocorticoid Receptor Antagonist ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
History Of

Background: The FIDELIO-DKD trial evaluated the effect of the nonsteroidal, selective mineralocorticoid receptor antagonist finerenone on kidney and cardiovascular (CV) outcomes in patients with chronic kidney disease (CKD) and type 2 diabetes (T2D) with optimized renin-angiotensin system blockade. Compared with placebo, finerenone reduced the composite kidney and CV outcomes. We report the effect of finerenone on individual CV outcomes and in patients with and without history of atherosclerotic CV disease (CVD). Methods: This randomized, double-blind, placebo-controlled trial included patients with T2D and urine albumin-to-creatinine ratio 30-5000 mg/g and an estimated glomerular filtration rate (eGFR) ≥25-<75 mL/min/1.73 m 2 , treated with optimized renin-angiotensin system blockade. Patients with a history of heart failure with reduced ejection fraction were excluded. Patients were randomized 1:1 to receive finerenone or placebo. The composite CV outcome included time to CV death, myocardial infarction, stroke, or hospitalization for heart failure. Prespecified CV analyses included analyses of the components of this composite and outcomes according to CVD history at baseline. Results: Between September 2015 and June 2018, 13,911 patients were screened and 5674 were randomized; 45.9% of patients had CVD at baseline. Over a median follow-up of 2.6 years (interquartile range, 2.0-3.4 years), finerenone reduced the risk of the composite CV outcome compared with placebo (hazard ratio [HR], 0.86; 95% confidence interval [CI], 0.75-0.99; P=0.034), with no significant interaction between patients with and without CVD (HR, 0.85; 95% CI, 0.71-1.01 in patients with a history of CVD; HR, 0.86; 95% CI, 0.68-1.08 in patients without a history of CVD; P-value for interaction, 0.85). The incidence of treatment-emergent adverse events was similar between treatment arms, with a low incidence of hyperkalemia-related permanent treatment discontinuation (2.3% with finerenone vs 0.8% with placebo in patients with CVD and 2.2% with finerenone vs 1.0% with placebo in patients without CVD). Conclusions: Among patients with CKD and T2D, finerenone reduced incidence of the composite CV outcome, with no evidence of differences in treatment effect based on pre-existing CVD status. Clinical Trial Registration: URL: https://clinicaltrials.gov Unique Identifier: NCT02540993 (Funded by Bayer AG)

scholarly journals TO001EFFECTS OF THE BET-INHIBITOR APABETALONE ON CARDIOVASCULAR EVENTS IN PATIENTS WITH TYPE 2 DIABETES MELLITUS AND ACUTE CORONARY SYNDROME, ACCORDING TO PRESENCE OR ABSENCE OF CHRONIC KIDNEY DISEASE. A BETONMACE TRIAL REPORT

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Kam Kalantar-Zadeh ◽  
Kausik K Ray ◽  
Stephen J Nicholls ◽  
Henry N Ginsburg ◽  
Kevin A Buhr ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Chronic Kidney Disease ◽  
Acute Coronary Syndrome ◽  
High Risk ◽  
Kidney Disease ◽  
Myocardial Infarct ◽  
Double Blind ◽  
Coronary Syndrome ◽  
Ckd Stage

Abstract Background and Aims Patients with type 2 diabetes (T2D) and acute coronary syndrome (ACS) are at high risk for recurrent cardiovascular (CV) events, particularly in the presence of chronic kidney disease (CKD). Apabetalone (APB) is a novel inhibitor of bromodomain and extraterminal (BET) proteins. Its cardiovascular efficacy and safety were evaluated in a phase 3 trial, BETonMACE. Method BETonMACE was a randomized, double-blind, comparison of effects of ABP or placebo (PBO) on major adverse CV events (MACE) defined as CV-death, non-fatal myocardial infarct or stroke, in 2425 pts with T2D and recent ACS. Here we report MACE plus CHF hospitalization in subjects with or without CKD Stage 3. Results Baseline characteristics: median age 62 years, 25.6% female, 87.6% white, 90% high intensity statin use, mean LDL-C 70.3 and HDL-C 33.3 mg/dl, median HbA1c 7.3%, and 11% with CKD Stage 3. Overall in the trial, MACE plus CHF hospitalization occurred in 139 (11.5%) patients with ABP and 173 (14.3%) with PBO (HR 0.78, 95% CI 0.63-0.98). In the subgroup with CKD, MACE plus CHF hospitalization occurred in 16 (12.9%) on APB and 41 (25%) on PBO (HR 0.48, 95% CI 0.26-0.89). In the subgroup without CKD, MACE plus CHF hospitalization occurred in 123 (11.3%) and 132 (12.7%) with APB or PBO, respectively (HR 0.89, 95% CI 0.70-1. Conclusion Patients with T2D, ACS, and Stage 3 CKD have a very high risk of subsequent MACE plus CHF hospitalization. The BET protein inhibitor ABP may reduce this risk.

scholarly journals Atrasentan and renal events in patients with type 2 diabetes and chronic kidney disease (SONAR): a double-blind, randomised, placebo-controlled trial

The Lancet ◽  
2019 ◽  
Vol 393 (10184) ◽  
pp. 1937-1947 ◽  
Author(s):  
Hiddo J L Heerspink ◽  
Hans-Henrik Parving ◽  
Dennis L Andress ◽  
George Bakris ◽  
Ricardo Correa-Rotter ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Controlled Trial ◽  
Double Blind
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