Pabon Maria A, Vardeny Orly, Vaduganathan Muthiah, Desai Akshay S, Claggett Brian L, Kulac Ian J, Jhund Pardeep S, Lam Carolyn S P, Senni Michele, Shah Sanjiv J, Voors Adriaan A, Zannad Faiez, Pitt Bertram, Saldarriaga Clara I, Petrie Mark C, Merkely Béla, Borentain Maria, Mueller Katharina, Viswanathan Prabhakar, Amarante Flaviana, Morris Alanna, McMurray John J V, Solomon Scott D
Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
Minneapolis VA Center for Care Delivery and Outcomes Research, University of Minnesota, Minneapolis.
JAMA Cardiol. 2025 May 21. doi: 10.1001/jamacardio.2025.1101.
Patients with chronic heart failure (HF) and left ventricular ejection fraction (LVEF) less than 40% who experience LVEF improvement to 40% or higher (HFimpEF) may still face residual risks.
To assess the clinical profiles, risk, and treatment response to finerenone in participants with HFimpEF.
DESIGN, SETTING, AND PARTICIPANTS: A total of 6001 patients with HE, LVEF of 40% or higher, New York Heart Association class II to IV symptoms, and elevated natriuretic peptide levels, were enrolled between September 14, 2020, and January 10, 2023. Patients with a prior history of LVEF less than 40% were included. Data analysis was conducted between September 1 to December 10, 2024.
Participants received finerenone (titrated to 20 mg or 40 mg) or placebo.
The primary end point was the composite of cardiovascular (CV) death and total (first and recurrent) worsening HF events.
Of the 6001 participants (mean [SD] age, 72 [9.7], years; 3269 male [55%]), 273 (5%) had a prior LVEF less than 40%. Among those with a prior LVEF of less than 40%, the median recorded prior LVEF was 35% [IQR, 30%-37%], with a median improvement of 12% [IQR, 8%-17%]. Over a median follow-up of 2.6 years, those with a history of LVEF of less than 40% experienced higher rates of the primary outcome of a composite of CV death and worsening of HF events (21.4 per 100 patient-years vs 16.0 per 100 patient-years) than did those whose LVEF was consistently 40% or higher. After adjustment for clinically relevant covariates; however, this rate ratio (RR) was not statistically different (absolute RR, 1.13; 95% CI, 0.85-1.49, P = .39). The treatment effect of finerenone on the primary outcome was consistent among those with a history of LVEF less than 40% and those with LVEF that was consistently 40% or higher (P for interaction = .36). Owing to higher baseline risk, the absolute risk reduction was greater among those with HFimpEF (9.2 vs 2.5 per 100 patient-years). Patients with HFimpEF tended to develop more hypotension with finerenone treatment, but otherwise, the safety profile of finerenone was similar in patients with and without previous LVEF less than 40%.
In this prespecified analysis of a randomized clinical trial, patients with HFimpEF remained at high risk of CV events, underscoring the need for continued management despite LVEF improvement. The treatment benefits of finerenone observed among the overall population of patients with HF with preserved EF were consistent among patients with HFimpEF.
ClinicalTrials.gov Identifier: NCT04435626.
慢性心力衰竭（HF）且左心室射血分数（LVEF）低于40%但LVEF改善至40%或更高（HFimpEF）的患者可能仍面临残余风险。
评估HFimpEF参与者的临床特征、风险及非奈利酮的治疗反应。
设计、设置和参与者：2020年9月14日至2023年1月10日期间共纳入6001例HF患者，LVEF为40%或更高，纽约心脏协会II至IV级症状，且利钠肽水平升高。纳入有LVEF低于40%既往史的患者。2024年9月1日至12月10日进行数据分析。
参与者接受非奈利酮（滴定至20mg或40mg）或安慰剂。
主要终点为心血管（CV）死亡和总的（首次和复发）HF恶化事件的复合终点。
在6001名参与者中（平均[标准差]年龄，72[9.7]岁；3269名男性[55%]），273名（5%）有LVEF低于40%的既往史。在既往LVEF低于40%的患者中，记录的既往LVEF中位数为35%[四分位间距，30%-37%]，改善中位数为12%[四分位间距，8%-17%]。在中位随访2.6年期间，有LVEF低于40%病史的患者发生CV死亡和HF事件恶化复合主要结局的发生率（每100患者年21.4例）高于LVEF持续为40%或更高的患者（每100患者年16.0例）。然而，在对临床相关协变量进行调整后，该率比（RR）无统计学差异（绝对RR为1.13；95%置信区间，0.85-1.49，P = 0.39）。非奈利酮对主要结局的治疗效果在有LVEF低于40%病史的患者和LVEF持续为40%或更高的患者中是一致的（交互作用P = 0.36）。由于基线风险较高，HFimpEF患者的绝对风险降低更大（每100患者年9.2例对2.5例）。HFimpEF患者接受非奈利酮治疗时更容易发生低血压，但除此之外，有或无既往LVEF低于40%的患者中非奈利酮的安全性概况相似。
在这项随机临床试验的预先指定分析中，HFimpEF患者仍有较高的CV事件风险，强调尽管LVEF有所改善但仍需持续管理。在射血分数保留的HF患者总体人群中观察到的非奈利酮治疗益处，在HFimpEF患者中是一致的。
ClinicalTrials.gov标识符：NCT04435626。
