Pitt Bertram, Agarwal Rajiv, Anker Stefan D, Rossing Peter, Ruilope Luis, Herzog Charles A, Greenberg Barry, Pecoits-Filho Roberto, Lambelet Marc, Lawatscheck Robert, Scalise Andrea, Filippatos Gerasimos
Department of Medicine, University of Michigan School of Medicine, Ann Arbor, MI 48109, USA.
Richard L. Roudebush VA Medical Center and Indiana University, Indianapolis, IN 46202, USA.
Eur Heart J Cardiovasc Pharmacother. 2025 Feb 8;11(1):10-19. doi: 10.1093/ehjcvp/pvae074.
Hypokalaemia is associated with cardiovascular events and mortality in patients with chronic kidney disease (CKD). This exploratory FIDELITY analysis, a prespecified pooled patient-dataset from FIDELIO-DKD and FIGARO-DKD, investigated the incidence and effect of hypokalaemia in patients with CKD and type 2 diabetes (T2D) treated with finerenone vs. placebo.
Outcomes include the incidence of treatment-emergent hypokalaemia (serum potassium <4.0 or <3.5 mmol/L) and the effect of finerenone on cardiovascular composite outcome (cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, or hospitalization for heart failure) and arrhythmia composite outcome (new diagnosis of atrial fibrillation/atrial flutter, hospitalization due to arrhythmia, or sudden cardiac death) by baseline serum potassium subgroups. In the FIDELITY population, treatment-emergent hypokalaemia with serum potassium <4.0 and <3.5 mmol/L occurred in 41.1% and 7.5%, respectively. Hazards of cardiovascular and arrhythmia composite outcomes were higher in patients with baseline serum potassium <4.0 vs. 4.0-4.5 mmol/L [hazard ratio (HR) 1.16; 95% confidence interval (CI) 1.02-1.32, P = 0.022 and HR 1.20; 95% CI 1.00-1.44, P = 0.055, respectively]. Finerenone reduced the incidence of hypokalaemia with serum potassium <4.0 mmol/L (HR 0.63; 95% CI 0.60-0.66) and <3.5 mmol/L (HR 0.46; 95% CI 0.40-0.53) vs. placebo. Finerenone lessened the hazard of cardiovascular and arrhythmia events vs. placebo, irrespective of baseline serum potassium.
A substantial proportion of patients with CKD and T2D experienced hypokalaemia, which was associated with an increased hazard of adverse cardiovascular outcomes. Finerenone reduced the incidence of hypokalaemia. Finerenone reduced the hazard of cardiovascular and arrhythmia outcomes irrespective of serum potassium subgroups. Clinical trials registration: FIDELIO-DKD and FIGARO-DKD are registered with ClinicalTrials.gov, numbers NCT02540993 and NCT02545049, respectively (funded by Bayer AG).
低钾血症与慢性肾脏病（CKD）患者的心血管事件及死亡率相关。这项探索性的FIDELITY分析，是来自FIDELIO-DKD和FIGARO-DKD预先设定的汇总患者数据集，研究了非奈利酮与安慰剂治疗的CKD合并2型糖尿病（T2D）患者中低钾血症的发生率及影响。
观察指标包括治疗引发的低钾血症（血清钾<4.0或<3.5 mmol/L）的发生率，以及非奈利酮对心血管复合结局（心血管死亡、非致死性心肌梗死、非致死性卒中或因心力衰竭住院）和心律失常复合结局（新发房颤/房扑诊断、因心律失常住院或心源性猝死）的影响，按基线血清钾亚组进行分析。在FIDELITY研究人群中，血清钾<4.0和<3.5 mmol/L的治疗引发低钾血症发生率分别为41.1%和7.5%。基线血清钾<4.0 mmol/L的患者与4.0 - 4.5 mmol/L的患者相比，心血管和心律失常复合结局的风险更高[风险比（HR）1.16；95%置信区间（CI）1.02 - 1.32，P = 0.022；HR 1.20；95% CI 1.00 - 1.44，P = 0.055]。与安慰剂相比，非奈利酮降低了血清钾<4.0 mmol/L（HR 0.63；95% CI 0.60 - 0.66）和<3.5 mmol/L（HR 0.46；95% CI 0.40 - 0.53）的低钾血症发生率。无论基线血清钾水平如何，与安慰剂相比，非奈利酮均降低了心血管和心律失常事件的风险。
相当比例的CKD合并T2D患者发生了低钾血症，这与不良心血管结局风险增加相关。非奈利酮降低了低钾血症的发生率。无论血清钾亚组情况如何，非奈利酮均降低了心血管和心律失常结局的风险。临床试验注册：FIDELIO-DKD和FIGARO-DKD已在ClinicalTrials.gov注册，注册号分别为NCT02540993和NCT02545049（由拜耳公司资助）。
