Division of Cardiology, Department of Internal Medicine, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan.
School of Medicine, National Yang-Ming University, Taipei, Taiwan.
ESC Heart Fail. 2024 Feb;11(1):198-208. doi: 10.1002/ehf2.14564. Epub 2023 Oct 27.
Patients with heart failure (HF) and reduced left ventricular ejection fraction (LVEF) accompanied by significant mitral regurgitation (MR) had poor outcome. Several vasodilator trials showed neutral results. We aimed to investigate the effect of early up-titration of hydralazine combined with conventional treatment in acute HF with severe systolic dysfunction and significant MR.
The study was open-labelled, one-to-one ratio randomized designed. Consecutively hospitalized patients with decompensated HF symptoms, LVEF < 35%, and MR more than moderate severity were enrolled after exclusion. All participants with inadequate preload should have intake promotion with/without fluid supply. Patients receiving evidence-based medications (EBMs) as conventional treatment served as the control. Hydralazine + conventional treatment group received up-titration of hydralazine at Days 1-5 of the index admission combined with EBMs and throughout the course of follow-up. The endpoints included cardiovascular (CV) death and HF rehospitalization. Totally, 408 patients were enrolled (203 in conventional treatment and 205 in hydralazine + conventional treatment). The mean follow-up period was 3.5 years. The mean dose of hydralazine was 191 mg at index admission and 264 mg at study end in hydralazine + conventional treatment group. Both groups did not significantly differ in prescription rates and dosages of EBMs (all P > 0.05) at study end. Side effects did not differ between the two groups. Finally, 51% (104 out of 203 cases) reached endpoints in conventional group and 34.6% (71 out of 205 cases) in hydralazine + conventional treatment group, which had a significant reduction in CV events (hazard ratio 0.613, 95% confidence interval 0.427-0.877, P < 0.001). In-hospital death during the index admission was significantly higher in conventional group (5.4% vs. 0.5%, respectively; P = 0.001).
When administered without inadequate preload, combining early up-titration of hydralazine with EBMs improves outcome in patients with severe systolic dysfunction and significant MR, and it is safe and well tolerated.
射血分数降低的心力衰竭（HF）伴严重二尖瓣反流（MR）患者预后不良。几项血管扩张剂试验结果为中性。本研究旨在探讨急性 HF 伴严重收缩功能障碍和显著 MR 患者早期肼屈嗪滴定联合常规治疗的效果。
该研究为开放标签、一对一比例随机设计。排除后，连续收治失代偿性 HF 症状、LVEF<35%和 MR 中度以上的患者。所有前负荷不足的患者均应摄入促进剂/液体补充。接受基于证据的药物（EBMs）作为常规治疗的患者作为对照组。肼屈嗪+常规治疗组在入院第 1-5 天接受肼屈嗪滴定，联合 EBMs 并在整个随访过程中进行。终点包括心血管（CV）死亡和 HF 再入院。共纳入 408 例患者（常规治疗组 203 例，肼屈嗪+常规治疗组 205 例）。平均随访时间为 3.5 年。肼屈嗪+常规治疗组入院时肼屈嗪平均剂量为 191mg，研究结束时为 264mg。两组在研究结束时 EBMs 的用药率和剂量均无显著差异（均 P>0.05）。两组不良反应无差异。最后，常规组有 51%（104/203 例）达到终点，肼屈嗪+常规治疗组有 34.6%（71/205 例）达到终点，CV 事件显著减少（风险比 0.613，95%置信区间 0.427-0.877，P<0.001）。常规组入院期间院内死亡明显较高（分别为 5.4%和 0.5%，P=0.001）。
在没有前负荷不足的情况下，肼屈嗪早期滴定联合 EBMs 可改善严重收缩功能障碍和显著 MR 患者的预后，且安全耐受良好。
