Looking into the Kinetics of NT-proBNP and sST2 Changes in Patients with Heart Failure Treated with Sacubitril/Valsartan: A Hint to Different Therapeutic Pathways.

IF 2.2 4区 医学 Q3 PHARMACOLOGY & PHARMACY
Drugs in Research & Development Pub Date : 2023-12-01 Epub Date: 2023-09-13 DOI:10.1007/s40268-023-00438-2
Massimo Mapelli, Irene Mattavelli, Elisabetta Salvioni, Alice Bonomi, Nicolò Capra, Pietro Palermo, Cristina Banfi, Stefania Paolillo, Maria Luisa Biondi, Piergiuseppe Agostoni
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引用次数: 1

Abstract

Background and objective: N-terminal pro-B-type natriuretic peptide (NT-proBNP) and soluble interleukin 1 receptor-like 1 ST2 (sST2) are biomarkers used to grade heart failure with reduced ejection fraction (HFrEF) severity. Both are potential targets of HFrEF treatment, but the first is associated with the patient's hemodynamic status, while the second is more indicative of the inflammatory status and of myocardial fibrosis. The aim of this study was to assess the kinetics of these biomarkers after treatment with sacubitril/valsartan in HFrEF.

Methods: We analyzed blood samples of patients with HFrEF at baseline (before sacubitril/valsartan treatment), after 1, 2, and 3 months (respectively, after a month taking the 24/26 - 49/51 - 97/103 mg twice daily, or b.i.d., doses), and 6 months after the maximum-tolerated dose was reached (end study).

Results: We obtained samples from 72 patients with HFrEF (age 64.0 ± 10.5 years, 83% males). NT-proBNP and sST2 values progressively and significantly reduced to 37% and 16%, respectively, with a greater reduction for NT-proBNP (p < 0.001). Specifically, NT-proBNP reduced from 1144 [593-2586] pg/mL to 743 [358-1524] pg/mL and sST2 from 27.3 [20.5-35.0] ng/mL to 23.1 [15.9-30.7] ng/mL, p for trend < 0.001 in both cases. The reduction of the two biomarkers over time occurred with statistically significant different kinetics: deferred for sST2 and faster for NT-proBNP. No significant changes in renal function and potassium levels were recorded.

Conclusion: These findings suggest that, in patients with HF, sacubitril/valsartan effects on the cardiovascular system share a double pathway: a first, hemodynamic, faster pathway and a second, non-hemodynamic anti-fibrotic, delayed one. Both likely contribute to the sacubitril/valsartan benefits in HFrEF.

Abstract Image

观察苏比利/缬沙坦治疗心力衰竭患者NT-proBNP和sST2变化的动力学:不同治疗途径的提示
背景和目的:n端前b型利钠肽(NT-proBNP)和可溶性白细胞介素1受体样1 ST2 (sST2)是用于分级射血分数降低(HFrEF)严重程度心力衰竭的生物标志物。两者都是HFrEF治疗的潜在靶点,但前者与患者的血流动力学状态有关,而后者更能指示炎症状态和心肌纤维化。本研究的目的是评估这些生物标志物在HFrEF中使用苏比里尔/缬沙坦治疗后的动力学。方法:我们分析了HFrEF患者的血液样本,分别在基线(sacubitril/缬沙坦治疗前),1、2和3个月(分别在服用24/26 - 49/51 - 97/103 mg,每日两次,或双剂量,1个月后)和达到最大耐受剂量6个月后(研究结束)。结果:我们获得了72例HFrEF患者的样本(年龄64.0±10.5岁,83%为男性)。NT-proBNP和sST2值分别逐渐显著降低至37%和16%,其中NT-proBNP降低幅度更大(p < 0.001)。具体而言,NT-proBNP从1144 [593-2586]pg/mL降至743 [358-1524]pg/mL, sST2从27.3 [20.5-35.0]ng/mL降至23.1 [15.9-30.7]ng/mL, p < 0.001。随着时间的推移,这两种生物标志物的减少具有统计学上显著的不同动力学:sST2延迟,NT-proBNP更快。肾功能和钾水平无明显变化。结论:这些研究结果表明,在HF患者中,沙比利/缬沙坦对心血管系统的作用有双重途径:第一种是血流动力学的快速途径,第二种是非血流动力学的抗纤维化延迟途径。这两种药物都可能有助于苏比里尔/缬沙坦治疗HFrEF的益处。
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来源期刊
Drugs in Research & Development
Drugs in Research & Development Pharmacology, Toxicology and Pharmaceutics-Pharmacology
CiteScore
5.10
自引率
0.00%
发文量
31
审稿时长
8 weeks
期刊介绍: Drugs in R&D is an international, peer reviewed, open access, online only journal, and provides timely information from all phases of drug research and development that will inform clinical practice. Healthcare decision makers are thus provided with knowledge about the developing place of a drug in therapy. The Journal includes: Clinical research on new and established drugs; Preclinical research of direct relevance to clinical drug development; Short communications and case study reports that meet the above criteria will also be considered; Reviews may also be considered.
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