Browsing by Subject "Hyperkalaemia"

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    Cardiovascular and kidney outcomes with finerenone in patients with type 2 diabetes and chronic kidney disease: the FIDELITY pooled analysis
    (Oxford University Press, 2022) Agarwal, Rajiv; Filippatos, Gerasimos; Pitt, Bertram; Anker, Stefan D.; Rossing, Peter; Joseph, Amer; Kolkhof, Peter; Nowack, Christina; Gebel, Martin; Ruilope, Luis M.; Bakris, George L.; Medicine, School of Medicine
    Aims: The complementary studies FIDELIO-DKD and FIGARO-DKD in patients with type 2 diabetes and chronic kidney disease (CKD) examined cardiovascular and kidney outcomes in different, overlapping stages of CKD. The purpose of the FIDELITY analysis was to perform an individual patient-level prespecified pooled efficacy and safety analysis across a broad spectrum of CKD to provide more robust estimates of safety and efficacy of finerenone compared with placebo. Methods and results: For this prespecified analysis, two phase III, multicentre, double-blind trials involving patients with CKD and type 2 diabetes, randomized 1:1 to finerenone or placebo, were combined. Main time-to-event efficacy outcomes were a composite of cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, or hospitalization for heart failure, and a composite of kidney failure, a sustained ≥57% decrease in estimated glomerular filtration rate from baseline over ≥4 weeks, or renal death. Among 13 026 patients with a median follow-up of 3.0 years (interquartile range 2.3-3.8 years), the composite cardiovascular outcome occurred in 825 (12.7%) patients receiving finerenone and 939 (14.4%) receiving placebo [hazard ratio (HR), 0.86; 95% confidence interval (CI), 0.78-0.95; P = 0.0018]. The composite kidney outcome occurred in 360 (5.5%) patients receiving finerenone and 465 (7.1%) receiving placebo (HR, 0.77; 95% CI, 0.67-0.88; P = 0.0002). Overall safety outcomes were generally similar between treatment arms. Hyperkalaemia leading to permanent treatment discontinuation occurred more frequently in patients receiving finerenone (1.7%) than placebo (0.6%). Conclusion: Finerenone reduced the risk of clinically important cardiovascular and kidney outcomes vs. placebo across the spectrum of CKD in patients with type 2 diabetes. Key question: Does finerenone, a novel selective, nonsteroidal mineralocorticoid receptor antagonist, added to maximum tolerated renin-angiotensin system inhibition reduce cardiovascular disease and kidney disease progression over a broad range of chronic kidney disease in patients with type 2 diabetes? Key finding: In a prespecified, pooled individual-level analysis from two randomized trials, we found reductions both in cardiovascular events and kidney failure outcomes with finerenone. Because 40% of the patients had an estimated glomerular filtration rate of >60 mL/min/1.73m2 they were identified solely on the basis of albuminuria. Take home message: Finerenone reduces the risk of clinical cardiovascular outcomes and kidney disease progression in a broad range of patients with chronic kidney disease and type 2 diabetes. Screening for albuminuria to identify at-risk patients among patients with type 2 diabetes facilitates reduction of both cardiovascular and kidney disease burden.
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    POS-829 Incidence and predictors of hyperkalaemia in patients with CKD and T2D in the FIDELIO-DKD trial
    (Elsevier, 2021) Agarwal, R.; Joseph, A.; Rossing, P.; Pitt, B.; Anker, D. S.; Filippatos, G.; Ruilope, M. L.; Kolkhof, P.; Scott, C.; Lawatscheck, R.; Bakris, L. G.; Medicine, School of Medicine
    Introduction: Patients with chronic kidney disease (CKD) and type 2 diabetes (T2D) have an increased risk of hyperkalaemia. Finerenone, a novel, selective, nonsteroidal, mineralocorticoid receptor antagonist, reduced the incidence of kidney and cardiovascular events in patients with CKD and T2D in the FIDELIO-DKD trial. This post hoc analysis describes the incidence and predictors of hyperkalaemia in FIDELIO-DKD. Methods: FIDELIO-DKD was a phase III, multicentre, double-blind trial that randomised 5734 patients (1:1) to finerenone or placebo. Patients with CKD, T2D and serum potassium ([K+]) ≤4.8 mmol/l at the run-in and screening visits, and treated with optimised renin–angiotensin system blockade were included. CKD was defined as a urine albumin-to-creatinine ratio (UACR) ≥30–<5000 mg/g and an estimated glomerular filtration rate (eGFR) ≥25–<75 ml/min/1.73 m2. Initial dosing of study drug (10 mg or 20 mg once daily [od]) was based on eGFR at screening. During the trial, study drug dosing was based on serum [K+] levels and eGFR changes, which were monitored at every study visit; the study drug was temporarily withheld if [K+] >5.5 mmol/l and restarted at 10 mg od when [K+] ≤5.0 mmol/l. In this safety analysis, hyperkalaemia was defined as an investigator-reported adverse event (AE) or by serum [K+] levels (>5.5 and >6.0 mmol/l); events were considered treatment-emergent if they occurred after the start of study drug administration and until 3 days after any interruption of study drug. Multivariate Cox proportional hazards regression was used to examine associations between baseline characteristics and first post-baseline treatment-emergent [K+] >5.5 or >6.0 mmol/l, adjusting for treatment assignment and baseline covariates chosen a priori based on clinical factors known to affect serum [K+]. A p‑value <0.05 was used to determine a significant association. Results: At baseline, 769/5658 (13.6%) and 390/5658 (6.9%) patients had [K+] >4.8 mmol/l and >5.0 mmol/l, respectively. After a median follow-up of 2.6 years, 44/2827 (1.6%) patients in the finerenone group and 12/2831 (0.4%) patients in the placebo group experienced a treatment-emergent hyperkalaemia-related serious AE. In the finerenone group, 64/2827 (2.3%) patients permanently discontinued the study drug due to hyperkalaemia, compared with 25/2831 (0.9%) patients in the placebo group. In total, 597/2785 (21.4%) and 256/2775 (9.2%) patients in the finerenone and placebo groups, respectively, had a treatment-emergent [K+] >5.5 mmol/l, while 126/2802 (4.5%) and 38/2796 (1.4%) patients, respectively, had a treatment-emergent [K+] >6.0 mmol/l. Selected baseline characteristics of patients with vs without any [K+] >5.5 or >6.0 mmol/l during the study are shown in the Table. The results of a multivariate analysis of hyperkalaemia risk factors will be presented. Conclusions: The K+ management protocol implemented in FIDELIO-DKD minimised the clinical impact of hyperkalaemia, as demonstrated by the low frequency of clinically meaningful hyperkalaemia-related serious AEs.
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    Should renin-angiotensin-aldosterone system inhibition enablement be a therapeutic target in CKD patients?
    (Oxford University Press, 2021) Rossignol, Patrick; Agarwal, Rajiv; Medicine, School of Medicine