Angiotensin-Neprilysin Inhibition and Left Ventricular Assist Device Therapy

IF 11.8 1区医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS

JACC. Heart failure Pub Date : 2025-08-31 DOI:10.1016/j.jchf.2025.102657

Maja Cikes MD, PhD , Jasper J. Brugts MD, PhD , Brian Claggett PhD , Ulrich P. Jorde MD , Davor Milicic MD, PhD , Ivo Planinc MD, PhD , Frank Ruschitzka MD, PhD , Nir Uriel MD, MSc , Ian Kulac MS , Nina Jakus MD, PhD , Filip Loncaric MD, PhD , Filip Puskaric MD , Dubravka Sipus MD , Hrvoje Gasparovic MD, PhD , Pawel Rubis MD, PhD , Linda W. van Laake MD, PhD , Igor Rudez MD, PhD , Marketa Hegarova MD, PhD , Gloria Sestan MD , Sylwia Wisniowska-Smialek MD, PhD , Scott D. Solomon MD

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引用次数: 0

Abstract

Background

The role of heart failure–specific therapies in left ventricular assist device (LVAD) recipients is unclear, and observational data suggest improved outcomes with neurohormonal blockers.

Objectives

ENVAD-HF (Multicenter, Randomized, Open-Label, Parallel Group, Study to Evaluate the Use of Sacubitril/Valsartan in HeartMate 3 LVAD Recipients) sought to evaluate the safety and tolerability of the angiotensin-neprilysin inhibitor sacubitril/valsartan vs standard of care (SOC) for managing blood pressure (BP) in HeartMate 3 LVAD recipients.

Methods

ENVAD-HF was a prospective multicenter, randomized, open-label study of sacubitril/valsartan vs SOC for managing BP (mean arterial pressure goal: 75-90 mm Hg) in stable LVAD recipients with 12-month follow-up. The composite primary endpoint was time to death, deterioration in renal function, hyperkalemia, or symptomatic hypotension leading to drug withdrawal. Exploratory endpoints included clinical and biomarker assessments and patient-reported outcomes.

Results

In 60 randomized patients (30 in each arm), sacubitril/valsartan compared with SOC demonstrated an HR of 0.42 (95% CI: 0.08-2.18; P = 0.30) for the primary endpoint at 12 months. Two primary endpoints were reached in the sacubitril/valsartan group (1 death and 1 symptomatic hypotension event) compared with 5 in the SOC group (2 deaths, 2 worsening renal function events, and 1 symptomatic hypotension event). Numerical trends in favor of sacubitril/valsartan were noted for other exploratory endpoints, including a reduced number of BP medications (difference: −1.09 [95% CI: −1.52 to −0.66]; P < 0.0001) and a significantly better Kansas City Cardiomyopathy Questionnaire–Overall Summary Score (improvement: +10.6 [95% CI: 2.6-18.7]; P = 0.011).

Conclusions

ENVAD-HF, a prospective randomized controlled trial of angiotensin-neprilysin inhibition in stable HeartMate 3 LVAD recipients, demonstrated the safety and tolerability of this therapy in this unique population. The trial forms the basis for a pivotal trial to investigate the usefulness of HF-specific therapies in the LVAD population. (Sacubitril/Valsartan in Left Ventricular Assist Device Recipients [ENVAD-HF], NCT04103554; A multicENter, randomized, open-label, parallel group, pilot study to evaluate the use of sacubitril/valsartan in HeartMate 3 LVAD recipients, 2019-003888-22)

查看原文本刊更多论文

血管紧张素- neprilysin抑制和左心室辅助装置治疗——多中心、随机、开放标签、平行组研究的主要结果，以评估sacubitril/缬沙坦在HeartMate 3型LVAD受者（ENVAD-HF）中的使用。

背景：LVAD受者心力衰竭特异性治疗的作用尚不清楚，观察数据表明神经激素阻滞剂可改善预后。ENVAD-HF评估血管紧张素- neprilysin抑制剂sacubitril/缬沙坦在心脏伴侣3 (HM3) LVAD患者与标准护理（SOC）患者血压（BP）控制方面的安全性和耐受性。方法：ENVAD-HF是一项前瞻性、多中心、随机、开放标签的研究，在稳定的LVAD受者中使用苏比利/缬沙坦或SOC来控制血压（MAP目标75- 90mmhg），随访12个月。复合主要终点为死亡时间、肾功能恶化、高钾血症或导致停药的症状性低血压。探索性终点包括临床和生物标志物评估以及患者报告的结果。结果：在60例随机患者中（每组30例），与SOC相比，苏比里尔/缬沙坦的HR为0.42,95% CI为0.08-2.18；12个月时主要终点P =0.30。sacubitril/缬沙坦组达到了两个主要终点（1例死亡和1例症状性低血压），而SOC组达到了5个主要终点（2例死亡，2例肾功能恶化事件和1例症状性低血压）。在其他探索性终点，包括降压药物的减少（差异：-1.09;95% CI: -1.52至-0.66,p），数值趋势也有利于沙比利/缬沙坦。结论：ENVAD-HF，一项对稳定HM3级LVAD受者进行血管紧张素-奈普利素抑制的前瞻性随机对照试验表明，该疗法在这一独特人群中具有安全性和耐受性。该试验为一项关键性试验奠定了基础，该试验旨在研究hf特异性治疗在LVAD人群中的有效性。临床试验注册：Clinicaltrials.gov: NCT04103554, draft: 2019-003888-22。

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来源期刊

JACC. Heart failure CARDIAC & CARDIOVASCULAR SYSTEMS-

CiteScore

21.20

自引率

2.30%

发文量

164

期刊介绍： JACC: Heart Failure publishes crucial findings on the pathophysiology, diagnosis, treatment, and care of heart failure patients. The goal is to enhance understanding through timely scientific communication on disease, clinical trials, outcomes, and therapeutic advances. The Journal fosters interdisciplinary connections with neuroscience, pulmonary medicine, nephrology, electrophysiology, and surgery related to heart failure. It also covers articles on pharmacogenetics, biomarkers, and metabolomics.