Browsing by Author "Roberts, Luke"

Now showing 1 - 3 of 3
  • Thumbnail Image
    Item
    Effects of canagliflozin versus finerenone on cardiorenal outcomes: exploratory post hoc analyses from FIDELIO-DKD compared to reported CREDENCE results
    (Oxford University Press, 2022) Agarwal, Rajiv; Anker, Stefan D.; Filippatos, Gerasimos; Pitt, Bertram; Rossing, Peter; Ruilope, Luis M.; Boletis, John; Toto, Robert; Umpierrez, Guillermo E.; Wanner, Christoph; Wada, Takashi; Scott, Charlie; Joseph, Amer; Ogbaa, Ike; Roberts, Luke; Scheerer, Markus F.; Bakris, George L.; FIDELIO-DKD investigators; Medicine, School of Medicine
    Background: The nonsteroidal mineralocorticoid receptor antagonist finerenone and the sodium-glucose cotransporter-2 inhibitor (SGLT-2i) canagliflozin reduce cardiorenal risk in albuminuric patients with chronic kidney disease (CKD) and type 2 diabetes (T2D). At first glance, the results of Finerenone in Reducing Kidney Failure and Disease Progression in Diabetic Kidney Disease (FIDELIO-DKD) (ClinicalTrials.gov, NCT02540993) and Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) appear disparate. In FIDELIO-DKD, the primary endpoint had an 18% [95% confidence interval (CI) 7-27] relative risk reduction; in CREDENCE, the primary endpoint had a 30% (95% CI 18-41) relative risk reduction. Unlike CREDENCE, the FIDELIO-DKD trial included patients with high albuminuria but excluded patients with symptomatic heart failure with reduced ejection fraction. The primary endpoint in the FIDELIO-DKD trial was kidney specific and included a sustained decline in the estimated glomerular filtration rate (eGFR) of ≥40% from baseline. In contrast, the primary endpoint in the CREDENCE trial included a sustained decline in eGFR of ≥57% from baseline and cardiovascular (CV) death. This post hoc exploratory analysis investigated how differences in trial design-inclusion/exclusion criteria and definition of primary outcomes-influenced observed treatment effects. Methods: Patients from FIDELIO-DKD who met the CKD inclusion criteria of the CREDENCE study (urine albumin: creatinine ratio >300-5000 mg/g and an eGFR of 30-<90 mL/min/1.73 m2 at screening) were included in this analysis. The primary endpoint was a cardiorenal composite (CV death, kidney failure, eGFR decrease of ≥57% sustained for ≥4 weeks or renal death). Patients with symptomatic heart failure with reduced ejection fraction were excluded from FIDELIO-DKD. Therefore, in a sensitivity analysis, we further adjusted for the baseline prevalence of heart failure. Results: Of 4619/5674 (81.4%) patients who met the subgroup inclusion criteria, 49.6% were treated with finerenone and 50.4% received placebo. The rate of the cardiorenal composite endpoint was 43.9/1000 patient-years with finerenone compared with 59.5/1000 patient-years with placebo. The relative risk was significantly reduced by 26% with finerenone versus placebo [hazard ratio (HR) 0.74 (95% CI 0.63-0.87)]. In CREDENCE, the rate of the cardiorenal composite endpoint was 43.2/1000 patient-years with canagliflozin compared with 61.2/1000 patient-years with placebo; a 30% risk reduction was observed with canagliflozin [HR 0.70 (95% CI 0.59-0.82)]. Conclusions: This analysis highlights the pitfalls of direct comparisons between trials. When key differences in trial design are considered, FIDELIO-DKD and CREDENCE demonstrate cardiorenal benefits of a similar magnitude.
  • Thumbnail Image
    Item
    Finerenone in Patients With Chronic Kidney Disease and Type 2 Diabetes by Sodium-Glucose Cotransporter 2 Inhibitor Treatment: The FIDELITY Analysis
    (American Diabetes Association, 2022-12) Rossing , Peter; Anker , Stefan D.; Filippatos , Gerasimos; Pitt, Bertram; Ruilope, Luis M.; Birkenfeld, Andreas L.; McGill, Janet B.; Rosas, Sylvia E.; Joseph, Amer; Gebel, Martin; Roberts, Luke; Scheerer, Markus F.; Bakris, George L.; Agarwal, Rajiv; FIDELIO-DKD Investigators; FIGARO-DKD Investigators; Medicine, School of Medicine
    OBJECTIVE Finerenone reduced the risk of kidney and cardiovascular events in people with chronic kidney disease (CKD) and type 2 diabetes in the FIDELIO-DKD and FIGARO-DKD phase 3 studies. Effects of finerenone on outcomes in patients taking sodium–glucose cotransporter 2 inhibitors (SGLT2is) were evaluated in a prespecified pooled analysis of these studies. RESEARCH DESIGN AND METHODS Patients with type 2 diabetes and urine albumin-to-creatinine ratio (UACR) ≥30 to ≤5,000 mg/g and estimated glomerular filtration rate (eGFR) ≥25 mL/min/1.73 m2 were randomly assigned to finerenone or placebo; SGLT2is were permitted at any time. Outcomes included cardiovascular composite (cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure) and kidney composite (kidney failure, sustained ≥57% eGFR decline, or renal death) end points, changes in UACR and eGFR, and safety outcomes. RESULTS Among 13,026 patients, 877 (6.7%) received an SGLT2i at baseline and 1,113 (8.5%) initiated one during the trial. For the cardiovascular composite, the hazard ratios (HRs) were 0.87 (95% CI 0.79–0.96) without SGLT2i and 0.67 (95% CI 0.42–1.07) with SGLT2i. For the kidney composite, the HRs were 0.80 (95% CI 0.69–0.92) without SGLT2i and 0.42 (95% CI 0.16–1.08) with SGLT2i. Baseline SGLT2i use did not affect risk reduction for the cardiovascular or kidney composites with finerenone (Pinteraction = 0.46 and 0.29, respectively); neither did SGLT2i use concomitant with study treatment. CONCLUSIONS Benefits of finerenone compared with placebo on cardiorenal outcomes in patients with CKD and type 2 diabetes were observed irrespective of SGLT2i use.
  • Thumbnail Image
    Item
    Finerenone Reduces New-Onset Atrial Fibrillation in Patients With Chronic Kidney Disease and Type 2 Diabetes
    (Elsevier, 2021) Filippatos, Gerasimos; Bakris, George L.; Pitt, Bertram; Agarwal, Rajiv; Rossing, Peter; Ruilope, Luis M.; Butler, Javed; Lam, Carolyn S. P.; Kolkhof, Peter; Roberts, Luke; Tasto, Christoph; Joseph, Amer; Anker, Stefan D.; FIDELIO-DKD Investigators; Medicine, School of Medicine
    Background: Patients with chronic kidney disease (CKD) and type 2 diabetes (T2D) are at risk of atrial fibrillation or flutter (AFF) due to cardiac remodeling and kidney complications. Finerenone, a novel, selective, nonsteroidal mineralocorticoid receptor antagonist, inhibited cardiac remodeling in preclinical models. Objectives: This work aims to examine the effect of finerenone on new-onset AFF and cardiorenal effects by history of AFF in the Finerenone in Reducing Kidney Failure and Disease Progression in Diabetic Kidney Disease (FIDELIO-DKD) study. Methods: Patients with CKD and T2D were randomized (1:1) to finerenone or placebo. Eligible patients had a urine albumin-to-creatinine ratio ≥30 to ≤5,000 mg/g, an estimated glomerular filtration rate (eGFR) ≥25 to <75 ml/min/1.73 m2 and received optimized doses of renin-angiotensin system blockade. Effect on new-onset AFF was evaluated as a pre-specified outcome adjudicated by an independent cardiologist committee. The primary composite outcome (time to first onset of kidney failure, a sustained decrease of ≥40% in eGFR from baseline, or death from renal causes) and key secondary outcome (time to first onset of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure) were analyzed by history of AFF. Results: Of 5,674 patients, 461 (8.1%) had a history of AFF. New-onset AFF occurred in 82 (3.2%) patients on finerenone and 117 (4.5%) patients on placebo (hazard ratio: 0.71; 95% confidence interval: 0.53-0.94; p = 0.016). The effect of finerenone on primary and key secondary kidney and cardiovascular outcomes was not significantly impacted by baseline AFF (interaction p value: 0.16 and 0.85, respectively). Conclusions: In patients with CKD and T2D, finerenone reduced the risk of new-onset AFF. The risk of kidney or cardiovascular events was reduced irrespective of history of AFF at baseline. (EudraCT 2015-000990-11 [A randomized, double-blind, placebo-controlled, parallel-group, multicenter, event-driven Phase III study to investigate the efficacy and safety of finerenone, in addition to standard of care, on the progression of kidney disease in subjects with type 2 diabetes mellitus and the clinical diagnosis of diabetic kidney disease]; Efficacy and Safety of Finerenone in Subjects With Type 2 Diabetes Mellitus and Diabetic Kidney Disease [FIDELIO-DKD]; NCT02540993).