ImportancePeople living with heart failure (HF) with mildly reduced or preserved ejection fraction have substantially curtailed life expectancy free from clinical events compared with their peers of comparable age. The nonsteroidal mineralocorticoid receptor antagonist, finerenone, was recently shown to reduce risks of cardiovascular events in this population over a median follow-up of 2.6 years; as patients with HF typically continue treatment beyond this time frame, estimating the potential long-term benefits of finerenone could inform shared clinical decision-making.ObjectiveTo estimate the projected long-term treatment effects of finerenone in patients with HF with mildly reduced or preserved ejection fraction if treated over a patient’s lifetime.Design, Setting, and ParticipantsPrespecified analyses were conducted of the FINEARTS-HF trial, a phase 3 randomized clinical trial conducted across 653 sites in 37 countries. Adults 40 years and older with symptomatic HF and left ventricular ejection fraction of 40% or greater were randomized from September 2020 to January 2023. Median (IQR) follow-up was 2.6 (1.9-3.0) years.InterventionsFinerenone (titrated to either 20 mg or 40 mg) or placebo.Main Outcomes and MeasuresThe primary composite outcome was time to cardiovascular death or worsening HF event. The long-term gains in survival free from a primary end point with finerenone were iteratively estimated with age-based Kaplan-Meier curves using age at randomization rather than time from randomization. Differences in areas under the survival curves between the finerenone and placebo arms represented event-free survival gains.ResultsAmong 6001 participants (median [IQR] age, 73 [66-79] years; 3269 male [54.5%]), mean survival free from the primary end point for a 55-year-old participant was 13.6 years (95% CI, 11.9-15.2 years) with finerenone and 10.5 years (95% CI, 6.8-11.3 years) with placebo, representing a gain in event-free survival of 3.1 years (95% CI, 0.8-5.4 years; P = .007). Mean event-free survival for a 65-year-old participant was 11.0 years (95% CI, 10.1-11.9 years) with finerenone and 8.9 years (95% CI, 8.1-9.8 years) with placebo, representing a gain of 2.0 years (95% CI, 0.8-3.3 years; P = .001). Projected mean event-free survival was numerically greater with finerenone than with placebo for every starting age between 50 to 80 years. Lifetime gains in event-free survival were observed even among individuals already treated with a sodium-glucose cotransporter 2 inhibitor (65-year-old participant: 3.1 years; 95% CI, 0.1-6.0 years; P = .04).Conclusions and RelevanceIn this prespecified secondary analysis of the FINEARTS-HF randomized clinical trial, long-term treatment with finerenone was estimated to extend event-free survival by up to 3 years among people with HF with mildly reduced or preserved ejection fraction.Trial RegistrationClinicalTrials.gov Identifier: NCT04435626.

中文翻译：

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Finerenone 对心力衰竭的估计长期益处


重要性与同龄人相比，射血分数轻度降低或保留的心力衰竭 （HF） 患者的预期寿命大大缩短，没有发生临床事件。非甾体盐皮质激素受体拮抗剂 finerenone 最近被证明可在中位随访 2.6 年期间降低该人群发生心血管事件的风险;由于 HF 患者通常会在此时间范围之后继续治疗，因此估计 finerenone 的潜在长期益处可以为共同的临床决策提供信息。目的评估 finerenone 对射血分数轻度降低或保留的 HF 患者的预期长期治疗效果，如果患者在患者的一生中接受治疗。对 FINEARTS-HF 试验进行了设计、设置和参与者预先指定的分析，这是一项在 37 个国家/地区的 653 个地点进行的 3 期随机临床试验。2020 年 9 月至 2023 年 1 月，40 岁及以上有症状的 HF 且左心室射血分数为 40% 或更高的成年人被随机分组。中位 （IQR） 随访时间为 2.6 （1.9-3.0） 年。干预措施Finerenone（滴定至 20 毫克或 40 毫克）或安慰剂。主要结局和测量主要复合结局是心血管死亡或 HF 事件恶化的时间。使用基于年龄的 Kaplan-Meier 曲线，使用随机化年龄而不是随机化时间，使用非利酮从主要终点迭代估计无主要终点的长期生存率增益。finerenone 组和安慰剂组之间生存曲线下面积的差异代表无事件生存期增加。结果在 6001 名参与者中 （中位 [IQR] 年龄，73 [66-79] 岁;3269 名男性 [54.5%]），55 岁参与者无主要终点的平均生存期为 13.6 年（95% CI，11.9-15.2 年），安慰剂组为 10.5 年（95% CI，6.8-11.3 年），无事件生存期增加 3.1 年（95% CI，0.8-5.4 年;P = .007）。一名 65 岁参与者的平均无事件生存期为 11.0 年 （95% CI，10.1-11.9 年），安慰剂组为 8.9 年 （95% CI，8.1-9.8 年），即增加 2.0 年 （95% CI，0.8-3.3 年;P = .001）。对于 50 至 80 岁之间的每个起始年龄，finerenone 组的预计平均无事件生存期在数值上高于安慰剂组。即使在已经接受钠-葡萄糖协同转运蛋白 2 抑制剂治疗的个体中，也观察到无事件生存期的终生增加 （65 岁参与者：3.1 岁;95% CI，0.1-6.0 年;P = .04）。结论和相关性在这项预先指定的 FINEARTS-HF 随机临床试验的二次分析中，估计使用 finerenone 长期治疗可将射血分数轻度降低或保留的 HF 患者的无事件生存期延长长达 3 年。试验 RegistrationClinicalTrials.gov 标识符：NCT04435626。