Finerenone, Serum Potassium, and Clinical Outcomes in Heart Failure With Mildly Reduced or Preserved Ejection Fraction.

Background

To investigate the frequency and predictors of serum potassium level greater than 5.5 mmol/L and less than 3.5 mmol/L and examine the treatment effect associated with finerenone, relative to placebo, on clinical outcomes based on postrandomization potassium levels.

本研究旨在调查血清钾水平大于5.5 mmol/L和小于3.5 mmol/L的频率和预测因素，并检查finerenone相对于安慰剂对基于随机化后钾水平的临床结果的影响。

DESIGN, SETTING, AND PARTICIPANTS: Secondary analysis of the FINEARTS-HF multicenter, randomized clinical trial, performed between September 14, 2020, and January 10, 2023, with a median follow-up of 32 months (final date of follow-up: June 14, 2024).

设计、环境和参与者：对FINEARTS-HF多中心、随机临床试验的二次分析，该试验于2020年9月14日至2023年1月10日进行，中位随访期为32个月（最后随访日期：2024年6月14日）。

Patients with heart failure and left ventricular ejection fraction greater than or equal to 40%, New York Heart Association class II to IV symptoms, and elevated natriuretic peptides were included.

纳入了心力衰竭患者，左心室射血分数大于或等于40%，纽约心脏协会II至IV级症状，以及心钠肽水平升高。

intervention

Participants received finerenone or placebo.

参与者接受了finerenone或安慰剂。

main_outcomes_and_measures

The primary outcome was a composite of total worsening heart failure events or cardiovascular death.

主要结果是总心力衰竭事件或心血管死亡的复合结果。

Results

A total of 6001 participants were included (3003 randomized to receive finerenone and 2998 randomized to receive placebo).

共有6001名参与者被纳入研究（其中3003人随机接受finerenone治疗，2998人随机接受安慰剂治疗）。

The increase in serum potassium was greater in the finerenone group than the placebo group at 1 month (median [IQR] difference, 0.19 [0.17-0.21] mmol/L) and 3 months (median [IQR] difference, 0.23 [0.21-0.25] mmol/L), which persisted for the remainder of trial follow-up.

在治疗1个月和3个月时，finerenone组的血清钾水平升高幅度大于安慰剂组（中位数[四分位数间距]差异分别为0.19 [0.17-0.21] mmol/L和0.23 [0.21-0.25] mmol/L），这种差异在随后的试验随访期间持续存在。

Finerenone increased the risks of potassium level increasing to greater than 5.5 mmol/L (hazard ratio[HR], 2.16 [95% CI, 1.83-2.56]; P < .001) and decreased the risks for potassium level decreasing to less than 3.5 mmol/L (HR, 0.46 [95% CI, 0.38-0.56]; P < .001).

Finerenone 增加了血钾水平升高至大于5.5 mmol/L的风险（风险比[HR]，2.16 [95% 置信区间，1.83-2.56]；P < .001），并降低了血钾水平降低至小于3.5 mmol/L的风险（HR，0.46 [95% 置信区间，0.38-0.56]；P < .001）。

Both low (< 3.5 mmol/L; HR, 2.49 [95% CI, 1.8-3.43]) and high (>5.5 mmol/L; HR, 1.64 [95% CI, 1.04-2.58]) potassium levels were associated with higher subsequent risks of the primary outcome in both treatment groups.

在两个治疗组中，低血钾水平（< 3.5 mmol/L；HR，2.49 [95% 置信区间，1.8-3.43]）和高血钾水平（>5.5 mmol/L；HR，1.64 [95% 置信区间，1.04-2.58]）都与随后主要结果的更高风险相关。

Nevertheless, the risk of the primary outcome was generally lower in patients treated with finerenone compared with placebo, even in those whose potassium level increased to greater than 5.5 mmol/L.

然而，与安慰剂相比，接受非奈利酮治疗的患者主要结果的风险普遍较低，即使在那些血钾水平升高至大于5.5毫摩尔/升的患者中也是如此。

conclusions_and_relevance

In patients with heart failure with mildly reduced or preserved ejection fraction, finerenone resulted in more frequent hyperkalemia and less frequent hypokalemia.

在射血分数轻度降低或保留的心力衰竭患者中，非奈利酮导致高钾血症的频率更高，低钾血症的频率更低。

However, with protocol-directed surveillance and dose adjustment, clinical benefit associated with finerenone relative to placebo was maintained even in those whose potassium level increased to greater than 5.5 mmol/L.

然而，在协议指导的监测和剂量调整下，与安慰剂相比，非奈利酮的临床益处即使在那些血钾水平升高至大于5.5 mmol/L的患者中也得以维持。

trial_registration

ClinicalTrials.gov Identifier: NCT04435626.

ClinicalTrials.gov 注册号：NCT04435626。