Filippatos Gerasimos, Anker Stefan D, Bakris George L, Rossing Peter, Ruilope Luis M, Coats Andrew J S, von Haehling Stephan, Ponikowski Piotr, Rosano Giuseppe M C, Brinker Meike, Farjat Alfredo E, Roberts Luke, Pitt Bertram
National and Kapodistrian University of Athens, School of Medicine Department of Cardiology, Attikon University Hospital, Athens, Greece.
Department of Cardiology (CVK) of German Heart Center Charité; German Centre for Cardiovascular Research (DZHK) partner site Berlin, Charité Universitätsmedizin, Berlin, Germany.
ESC Heart Fail. 2025 Feb;12(1):185-188. doi: 10.1002/ehf2.14962. Epub 2024 Sep 3.
Left ventricular hypertrophy (LVH) has been associated with an increased risk of cardiovascular (CV) disease and linked to increased morbidity and mortality. In patients with chronic kidney disease (CKD) and type 2 diabetes (T2D), hypertension is common, and patients with these co-morbidities additionally have a high prevalence of LVH. This analysis of the prespecified pooled FIDELITY analysis comprising the randomized, double-blind, placebo-controlled, multicentre FIDELIO-DKD and FIGARO-DKD phase III studies aimed to explore the CV and kidney effects of finerenone, a nonsteroidal mineralocorticoid receptor antagonist, in patients with CKD and T2D stratified by a diagnosis of LVH at baseline.
A diagnosis of LVH in the FIDELITY patient population was determined at baseline using investigator-reported electrocardiogram (ECG) findings. The two efficacy outcomes, assessed by baseline LVH, were the composite CV outcome of time to CV death, non-fatal myocardial infarction, non-fatal stroke, or hospitalization for heart failure (HHF), and a composite kidney outcome of time to onset of kidney failure, a sustained decrease in estimated glomerular filtration rate (eGFR) ≥57% from baseline over ≥4 weeks, or kidney-related death. Safety outcomes by baseline LVH were reported as treatment-emergent adverse events. At baseline out of 13 026 patients in FIDELITY, 96.5% had hypertension and 9.6% had investigator-reported LVH. The relative risk reduction for the composite CV and kidney outcomes with finerenone versus placebo was lower in the LVH subgroup; however, the treatment effect of finerenone was not modified by baseline LVH for either outcome (P = 0.1075 for composite CV outcome and P = 0.1782 for composite kidney outcome). Analysis of the composite CV outcome components showed a greater reduction in the risk of HHF versus placebo for patients with baseline LVH compared with those without (P = 0.0024). Overall safety events were comparable between the LVH subgroups and treatment arms. Treatment-emergent hyperkalaemia was observed more frequently with finerenone versus placebo, but discontinuation rates were low in both treatment arms and between LVH subgroups.
In conclusion, the overall CV and kidney benefits of finerenone versus placebo were not modified by the presence of LVH at baseline, with overall safety findings being similar between LVH subgroups. A greater benefit was observed for HHF in patients with versus without LVH, suggesting that LVH may be a predictor of the treatment effect of finerenone on HHF.
左心室肥厚（LVH）与心血管（CV）疾病风险增加相关，并与发病率和死亡率升高有关。在慢性肾脏病（CKD）和2型糖尿病（T2D）患者中，高血压很常见，且合并这些疾病的患者LVH患病率也很高。这项针对预先指定的汇总FIDELITY分析进行的研究，该分析纳入了随机、双盲、安慰剂对照、多中心的III期FIDELIO-DKD和FIGARO-DKD研究，旨在探讨非甾体类盐皮质激素受体拮抗剂非奈利酮对基线时根据LVH诊断分层的CKD和T2D患者的心血管和肾脏影响。
在FIDELITY研究人群中，根据研究人员报告的心电图（ECG）结果在基线时确定LVH诊断。通过基线LVH评估的两个疗效结局分别是心血管死亡、非致命性心肌梗死、非致命性中风或因心力衰竭住院（HHF）的复合心血管结局，以及肾衰竭发生时间、估计肾小球滤过率（eGFR）从基线持续下降≥57%且持续≥4周或肾脏相关死亡的复合肾脏结局。根据基线LVH报告的安全性结局为治疗期间出现的不良事件。在FIDELITY研究的13026例患者中，96.5%患有高血压，9.6%有研究人员报告的LVH。与安慰剂相比，非奈利酮治疗组中LVH亚组的复合心血管和肾脏结局的相对风险降低较低；然而，对于任何一个结局，非奈利酮的治疗效果均未因基线LVH而改变（复合心血管结局P = 0.1075，复合肾脏结局P = 0.1782）。对复合心血管结局组成部分的分析显示，与无基线LVH的患者相比，有基线LVH的患者与安慰剂相比，HHF风险降低幅度更大（P = 0.0024）。LVH亚组和治疗组之间的总体安全事件相当。与安慰剂相比，非奈利酮治疗期间高钾血症的发生率更高，但两个治疗组以及LVH亚组之间的停药率均较低。
总之，基线时LVH的存在并未改变非奈利酮与安慰剂相比在心血管和肾脏方面的总体获益，LVH亚组之间的总体安全性结果相似。与无LVH的患者相比，有LVH的患者在HHF方面获益更大，这表明LVH可能是非奈利酮对HHF治疗效果的一个预测指标。
