ImportanceTreatment with finerenone, a nonsteroidal mineralocorticoid receptor antagonist (MRA), improved outcomes in patients with heart failure with mildly reduced or preserved ejection fraction in FINEARTS-HF, but was associated with increased levels of serum potassium in follow-up.ObjectiveTo 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.Design, Setting, and ParticipantsSecondary 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). 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.InterventionParticipants received finerenone or placebo.Main Outcomes and MeasuresThe primary outcome was a composite of total worsening heart failure events or cardiovascular death.ResultsA total of 6001 participants were included (3003 randomized to receive finerenone and 2998 randomized to receive placebo). 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. 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). 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. 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.Conclusions and RelevanceIn patients with heart failure with mildly reduced or preserved ejection fraction, finerenone resulted in more frequent hyperkalemia and less frequent hypokalemia. 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.Trial RegistrationClinicalTrials.gov Identifier: NCT04435626

中文翻译：

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非奈利酮、血清钾和射血分数轻度降低或保留的心力衰竭的临床结局


重要性 非甾体盐皮质激素受体拮抗剂 （MRA） finerenone 治疗可改善 FINEARTS-HF 射血分数轻度降低或保留的心力衰竭患者的预后，但与随访中血清钾水平升高有关。目的探讨血钾水平大于 5.5 mmol/L 和低于 3.5 mmol/L 的频率和预测因素，并探讨相对于安慰剂相比，非利酮相对于安慰剂相关的治疗效果对基于随机化后钾水平的临床结局的影响。设计、设置和参与者FINEARTS-HF 多中心随机临床试验的二次分析，于 2020 年 9 月 14 日至 2023 年 1 月 10 日进行，中位随访 32 个月（最终随访日期：2024 年 6 月 14 日）。包括心力衰竭和左心室射血分数大于或等于 40% 、纽约心脏协会 II 至 IV 级症状和利钠肽升高的患者。干预受试者接受 finerenone 或安慰剂。主要结局和测量主要结局是总恶化的心力衰竭事件或心血管死亡的复合结局。结果共纳入 6001 名参与者 （3003 名随机接受 finerenone，2998 名随机接受安慰剂）。非奈利酮组在 1 个月 （中位 [IQR] 差异，0.19 [0.17-0.21] mmol/L） 和 3 个月 （中位 [IQR] 差异，0.23 [0.21-0.25] mmol/L）时血清钾的增加大于安慰剂组，这种情况在试验随访的剩余时间内持续存在。非奈利酮使钾水平升高的风险增加至大于 5.5 mmol/L （风险比 [HR]，2.16 [95% CI，1.83-2.56];P < .001），并将钾水平降至 3.5 mmol/L 以下的风险降低 （HR，0.46 [95% CI，0.38-0.56];P < .001）。均低 （< 3.5 mmol/L;HR，2.49 [95% CI，1.8-3.43]） 和高 （>5.5 毫摩尔/升;HR，1.64 [95% CI，1.04-2.58]） 钾水平与两个治疗组主要结局的较高后续风险相关。然而，与安慰剂相比，接受 finerenone 治疗的患者发生主要结局的风险通常较低，即使在钾水平升高至 5.5 mmol/L 的患者中也是如此。结论和相关性在射血分数轻度降低或保留的心力衰竭患者中，finerenone 导致更频繁的高钾血症和较少的低钾血症。然而，通过方案指导的监测和剂量调整，即使在钾水平升高至 5.5 mmol/L 以上的患者中，非利酮相对于安慰剂相关的临床益处也能维持。gov 标识符： NCT04435626