Department of Cardiovascular Medicine, Saga University, 5-1-1 Nabeshima, Saga 849-8501, Japan.
Department of Pharmacology, St. Marianna University School of Medicine, Kawasaki, Japan.
Eur Heart J. 2024 Nov 8;45(42):4482-4493. doi: 10.1093/eurheartj/ehae561.
The efficacy and safety of early sacubitril/valsartan (Sac/Val) initiation after acute heart failure (AHF) has not been demonstrated outside North America. The present study aimed to evaluate the effect of in-hospital Sac/Val therapy initiation after an AHF episode on N-terminal pro-B-type natriuretic peptide (NT-proBNP) level in Japanese patients.
This was an investigator-initiated, multicentre, prospective, randomized, open-label, blinded-endpoint pragmatic trial. After haemodynamic stabilization within 7 days after hospitalization, eligible inpatients were allocated to switch from angiotensin-converting enzyme inhibitor or angiotensin receptor blocker to Sac/Val (Sac/Val group) or to continue angiotensin-converting enzyme inhibitor or angiotensin receptor blocker (control group). The primary efficacy endpoint was the 8-week proportional change in geometric means of NT-proBNP levels.
A total of 400 patients were equally randomized, and 376 (median age 75 years, 31.9% women, de novo heart failure rate 55.6%, and median left ventricular ejection fraction 37%) were analysed. The per cent changes in NT-proBNP level geometric means at Weeks 4/8 were -35%/-45% (Sac/Val group) and -18%/-32% (control group), and their group ratio (Sac/Val vs. control) was 0.80 (95% confidence interval 0.68-0.94; P = .008) at Week 4 and 0.81 (95% confidence interval 0.68-0.95; P = .012) at Week 8, respectively. In the pre-specified subgroup analyses, the effects of Sac/Val were confined to patients with a left ventricular ejection fraction < 40% and were more evident in those in sinus rhythm and taking mineralocorticoid receptor antagonists. No adverse safety signal was evident.
In-hospital Sac/Val therapy initiation in addition to contemporary recommended therapy triggered a greater NT-proBNP level reduction in Japanese patients hospitalized for AHF. These findings may expand the evidence on Sac/Val therapy in this clinical situation outside North America.
ClinicalTrial.gov (NCT05164653) and Japan Registry of Clinical Trials (jRCTs021210046).
在北美以外地区，尚未证实急性心力衰竭（AHF）后早期起始沙库巴曲缬沙坦（Sac/Val）的疗效和安全性。本研究旨在评估 AHF 发作后住院期间开始 Sac/Val 治疗对日本患者 N 末端 B 型利钠肽前体（NT-proBNP）水平的影响。
这是一项由研究者发起的、多中心、前瞻性、随机、开放标签、盲终点实用临床试验。在住院后 7 天内血流动力学稳定后，合格的住院患者被分配为从血管紧张素转换酶抑制剂或血管紧张素受体阻滞剂转换为 Sac/Val（Sac/Val 组）或继续使用血管紧张素转换酶抑制剂或血管紧张素受体阻滞剂（对照组）。主要疗效终点是 8 周时 NT-proBNP 水平几何均数的比例变化。
共随机分配了 400 名患者，376 名（中位年龄 75 岁，31.9%为女性，新发心力衰竭率为 55.6%，中位左心室射血分数为 37%）患者进行了分析。第 4/8 周时 NT-proBNP 水平几何均数的变化百分比分别为 -35%/-45%（Sac/Val 组）和 -18%/-32%（对照组），其组间比值（Sac/Val 与对照组）分别为 0.80（95%置信区间 0.68-0.94；P =.008）在第 4 周和 0.81（95%置信区间 0.68-0.95；P =.012）在第 8 周。在预先指定的亚组分析中，Sac/Val 的作用仅限于左心室射血分数 < 40%的患者，并且在窦性节律和使用盐皮质激素受体拮抗剂的患者中更为明显。没有发现不良安全信号。
在日本因 AHF 住院的患者中，除了当前推荐的治疗方法外，额外添加住院期间开始 Sac/Val 治疗可更大程度地降低 NT-proBNP 水平。这些发现可能会在北美以外的临床环境中进一步证实 Sac/Val 治疗的疗效。
ClinicalTrials.gov（NCT05164653）和日本临床试验注册（jRCTs021210046）。
