AimsSerelaxin is recombinant human relaxin‐2, a hormone responsible for haemodynamic adaptations and organ protection in pregnancy. In the RELAX‐AHF trial, serelaxin demonstrated reductions in cardiac, renal and hepatic damage. In RELAX‐AHF‐2, organ damage‐related biomarkers were assessed in a biomarker substudy.Methods and resultsPatients enrolled within 16 h of presentation for heart failure hospitalization were randomized to 48‐h infusions of either serelaxin (30 μg/kg/day) or placebo, and plasma samples were obtained at baseline, 2, 5, and 14 days in patients participating in the biomarker substudy. Of the 6545 patients analysed in RELAX‐AHF‐2, 1020 (15.6%) patients (mean age 72 ± 12 years; 61% male) were enrolled in the biomarker substudy. Compared to placebo, serelaxin decreased percentage change from baseline in troponin T through day 14 (serelaxin +0.2% vs. placebo +40.3%; p = 0.042), as well as creatinine (−0.8% vs. +5.8%; p = 0.002), cystatin C (+3.8% vs. +8.3%; p = 0.016), and uric acid (+0.8% vs. +7.2%; p = 0.0014) at day 2. The decrease of N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP) from baseline to day 2 was greater in serelaxin‐treated patients (−39.8% vs. −27.6%; p = 0.002). Early changes in NT‐proBNP and troponin, but not creatinine, cystatin C and uric acid, were associated with 180‐day mortality. In this substudy population, serelaxin did not reduce 180‐day cardiovascular death (hazard ratio [HR] 0.78; 95% confidence interval [CI] 0.49–1.25; p = 0.30), but significantly reduced worsening heart failure through day 5 (HR 0.55; 95% CI 0.33–0.93; p = 0.027).ConclusionIn this substudy, serelaxin decreased plasma concentrations of cardiac, renal and hepatic injury markers. Changes of most of these markers were associated with cardiovascular mortality. In this pre‐specified biomarker subgroup, serelaxin did not reduce 180‐day cardiovascular mortality but significantly reduced worsening heart failure through day 5.

中文翻译：

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serelaxin 对心力衰竭住院患者的终末器官保护作用：急性心力衰竭松弛素生物标志物子研究结果 （RELAX-AHF-2）


AimsSerelaxin 是重组人松弛素-2，一种负责妊娠期血流动力学适应和器官保护的激素。在 RELAX-AHF 试验中，serelaxin 显示心脏、肾脏和肝脏损伤减少。在 RELAX-AHF-2 中，在生物标志物子研究中评估了与器官损伤相关的生物标志物。方法和结果在心力衰竭住院后 16 小时内入组的患者被随机分配到 48 小时输注 serelaxin （30 μg/kg/天） 或安慰剂组，并在基线、 2 、 5 和 14 天获得血浆样本参与生物标志物子研究的患者。在 RELAX-AHF-2 分析的 6545 名患者中，1020 名 （15.6%） 患者 （平均年龄 72 ± 12 岁;61% 为男性） 被纳入生物标志物子研究。与安慰剂相比，第14天肌钙蛋白T相对于基线的百分比变化降低（血清松弛素+0.2%vs安慰剂+40.3%;p = 0.042），以及肌酐（-0.8% vs. +5.8%;p = 0.002）、胱抑素C（+3.8% vs. +8.3%;p = 0.016）和尿酸（+0.8% vs. +7.2%;p = 0.0014）在第2天。在接受 serelaxin 治疗的患者中，N 末端 B 型利钠肽前体 （NT-proBNP） 从基线到第 2 天的降低幅度更大 （-39.8% vs. -27.6%;p = 0.002）。NT-proBNP 和肌钙蛋白的早期变化，但肌酐、胱抑素 C 和尿酸的早期变化与 180 天死亡率相关。在该子研究人群中，serelaxin 没有减少 180 天的心血管死亡 （风险比 [HR] 0.78;95% 置信区间 [CI] 0.49-1.25;p = 0.30），但显著减少了第 5 天的心力衰竭恶化 （HR 0.55;95% CI 0.33-0.93;p = 0.027）。结论在本子研究中，serelaxin 降低了心脏、肾脏和肝脏损伤标志物的血浆浓度。 这些标志物中的大多数变化与心血管死亡率相关。在这个预先指定的生物标志物亚组中，serelaxin 没有降低 180 天的心血管死亡率，但显着减少了第 5 天的心力衰竭恶化。