Department of Cardiology, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan.
University of Missouri's Healthcare Institute for Innovations in Quality and Saint Luke's Mid America Heart Institute, Kansas City, Missouri, USA.
BMJ Open. 2024 Feb 14;14(2):e076519. doi: 10.1136/bmjopen-2023-076519.
The current guidelines strongly recommend early initiation of multiple classes of cardioprotective drugs for patients with heart failure with reduced ejection fraction to improve prognosis and health status. However, evidence on the optimal sequencing of approved drugs is scarce, highlighting the importance of individualised treatment plans. Registry data indicate that only a portion of these patients can tolerate all four recommended classes, underscoring the need to establish the favoured sequence when using these drugs. Additionally, the choice between long-acting and short-acting loop diuretics in the present era remains uncertain. This is particularly relevant given the frequent use of angiotensin receptor-neprilysin inhibitor and sodium-glucose cotransporter 2 inhibitor, both of which potentiate natriuretic effects.
In a prospective, randomised, open-label, blinded endpoint method, LAQUA-HF (Long-acting vs short-acting diuretics and neurohormonal Agents on patients' QUAlity-of-life in Heart Failure patients) will be a 2×2 factorial design, with a total of 240 patients randomised to sacubitril/valsartan versus dapagliflozin and torsemide versus furosemide in a 1:1 ratio. Most enrolment sites have participated in an ongoing observational registry for consecutive patients hospitalised for heart failure involved dedicated study coordinators, and used the same framework to enrol patients. The primary endpoint is the change in patients' health status over 6 months, defined by the Kansas City Cardiomyopathy Questionnaire. Additionally, clinical benefit at 6 months defined as a hierarchical composite endpoint will be assessed by the win ratio as the secondary endpoint.
The medical ethics committee Keio University in Japan has approved this trial. All participants provide written informed consent prior to study entry. The results of this trial will be disseminated in one main paper and additional papers on secondary endpoints and subgroup analyses.
UMIN000045229.
目前的指南强烈建议射血分数降低的心力衰竭患者早期开始使用多种类别的心脏保护药物，以改善预后和健康状况。然而，关于批准药物的最佳序贯应用的证据很少，这突显了制定个体化治疗方案的重要性。登记数据表明，只有一部分患者可以耐受所有四类推荐药物，这强调了在使用这些药物时确定首选药物顺序的必要性。此外，在当前时代，长效和短效袢利尿剂的选择仍然不确定。这一点尤其重要，因为血管紧张素受体-脑啡肽酶抑制剂和钠-葡萄糖共转运蛋白 2 抑制剂的使用频率很高，这两种药物都增强了利钠作用。
在一项前瞻性、随机、开放标签、盲终点的方法中，LAQUA-HF（长效与短效利尿剂和神经激素制剂对心力衰竭患者生活质量的影响）将采用 2×2 析因设计，总共 240 例患者随机分为沙库巴曲缬沙坦组与达格列净组和托塞米组与呋塞米组，比例为 1:1。大多数入组地点都参与了一项连续的心力衰竭住院患者观察性登记研究，配备了专门的研究协调员，并使用相同的框架入组患者。主要终点是 6 个月内患者健康状况的变化，定义为堪萨斯城心肌病问卷。此外，6 个月时的临床获益定义为分层复合终点，将通过赢率作为次要终点进行评估。
日本庆应义塾大学的医学伦理委员会已批准该试验。所有参与者在入组前均提供书面知情同意书。该试验的结果将在一篇主要论文和其他关于次要终点和亚组分析的论文中公布。
UMIN000045229。
