Chimura Misato, Jhund Pardeep S, Henderson Alasdair D, Yang Mingming, Claggett Brian L, Desai Akshay S, Rohwedder Katja, Lage Andrea, Scalise Andrea, Mueller Katharina, Schou Morten, Lam Carolyn S P, Senni Michele, Voors Adriaan A, Zannad Faiez, Pitt Bertram, Vaduganathan Muthiah, Solomon Scott D, McMurray John J V
British Heart Foundation Cardiovascular Research Centre, University of Glasgow, Glasgow, United Kingdom.
Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, Suita, Japan.
JAMA Cardiol. 2025 Aug 13. doi: 10.1001/jamacardio.2025.2551.
Given their kidney actions, it is important to evaluate the efficacy and safety of mineralocorticoid receptor antagonists when combined with other diuretics and whether they have a so-called diuretic-sparing effect in patients with heart failure (HF).
To examine the efficacy and tolerability of finerenone related to background diuretic treatment in patients with heart failure with mildly reduced or preserved ejection fraction (HFmrEF/HFpEF).
DESIGN, SETTING, AND PARTICIPANTS: This study is a prespecified secondary analysis of the FINEARTS-HF (Finerenone Trial to Investigate Efficacy and Safety Superior to Placebo in Patients With Heart Failure) randomized clinical trial, which was conducted across 653 sites in 37 countries among adults aged 40 years and older with HFmrEF/HFpEF, who were randomized between September 2020 and January 2023. Data analysis was conducted from December 1, 2024, to January 30, 2025.
Finerenone (titrated to 20 mg or 40 mg) or placebo.
The primary outcome was the composite of total HF events and cardiovascular death. Outcomes were compared between finerenone and placebo according to the following baseline diuretic categories: only a nonloop diuretic (thiazide or thiazide-like); loop diuretic (≤40 mg vs >40 mg furosemide-equivalent dose); and combined nonloop and loop diuretic use.
Among 5438 patients, 2496 (45.9%) were female, and mean (SD) age was 72.1 (9.6) years. A total of 684 patients (12.6%) were receiving a nonloop diuretic, 3040 (55.9%) less than or equal to 40 mg furosemide equivalent, 1145 (21.1%) 40 mg or greater furosemide equivalent, and 569 (10.5%) both nonloop and loop diuretics. Compared with placebo, finerenone reduced the risk of the primary end point across all diuretic subgroups: rate ratios were 0.84 (95% CI, 0.47-1.51), 0.86 (95% CI, 0.72-1.02), 0.98 (95% CI, 0.78-1.24), and 0.54 (95% CI, 0.35-0.83) for patients in the nonloop, 40 mg or less loop, more than 40 mg loop, and combined nonloop and loop categories, respectively (P for interaction = .18). Compared with placebo, finerenone reduced loop diuretic dose and dose intensification, but not loop diuretic initiation. Safety was consistent across diuretic categories.
In this secondary analysis of the FINEARTS-HF randomized clinical trial, the efficacy and safety of finerenone were consistent across all diuretic subgroups. Compared with placebo, finerenone reduced the use of diuretics in patients with HFmrEF/HFpEF; however, finerenone did not reduce the initiation of new loop diuretic in participants not receiving a loop diuretic at baseline.
ClinicalTrials.gov Identifier: NCT04435626.
鉴于盐皮质激素受体拮抗剂对肾脏的作用，评估其与其他利尿剂联合使用时的疗效和安全性，以及它们在心力衰竭（HF）患者中是否具有所谓的利尿节省效应非常重要。
研究非奈利酮在轻度射血分数降低或保留的心力衰竭（HFmrEF/HFpEF）患者中与背景利尿剂治疗相关的疗效和耐受性。
设计、设置和参与者：本研究是FINEARTS-HF（非奈利酮在心力衰竭患者中疗效和安全性优于安慰剂的试验）随机临床试验的预先指定的二次分析，该试验在37个国家的653个地点对年龄在40岁及以上的HFmrEF/HFpEF成年患者进行，这些患者于2020年9月至2023年1月期间被随机分组。数据分析于2024年12月1日至2025年1月30日进行。
非奈利酮（滴定至20mg或40mg）或安慰剂。
主要结局是总心力衰竭事件和心血管死亡的复合结局。根据以下基线利尿剂类别比较非奈利酮和安慰剂的结局：仅使用非襻利尿剂（噻嗪类或噻嗪样利尿剂）；襻利尿剂（呋塞米等效剂量≤40mg与>40mg）；以及联合使用非襻利尿剂和襻利尿剂。
在5438例患者中，2496例（45.9%）为女性，平均（标准差）年龄为72.1（9.6）岁。共有684例患者（12.6%）接受非襻利尿剂治疗，3040例（55.9%）接受相当于40mg或更低剂量的呋塞米治疗，1145例（21.1%）接受相当于40mg或更高剂量的呋塞米治疗，569例（10.5%）同时接受非襻利尿剂和襻利尿剂治疗。与安慰剂相比，非奈利酮在所有利尿剂亚组中均降低了主要终点风险：非襻利尿剂组、40mg或更低剂量襻利尿剂组、超过40mg襻利尿剂组以及联合使用非襻利尿剂和襻利尿剂组患者的率比分别为0.84（95%CI，0.47-1.51）、0.86（95%CI，0.72-1.02）、0.98（95%CI，0.78-1.24）和0.54（95%CI，0.35-0.83）（交互作用P=0.18）。与安慰剂相比，非奈利酮降低了襻利尿剂剂量和剂量强化，但未降低襻利尿剂的起始使用。各利尿剂类别之间的安全性一致。
在FINEARTS-HF随机临床试验的这项二次分析中，非奈利酮在所有利尿剂亚组中的疗效和安全性一致。与安慰剂相比，非奈利酮减少了HFmrEF/HFpEF患者的利尿剂使用；然而，非奈利酮并未降低基线时未接受襻利尿剂治疗的参与者中新襻利尿剂的起始使用。
ClinicalTrials.gov标识符：NCT04435626。
