Heart Failure Therapeutics on the Basis of a Biased Ligand of the Angiotensin-2 Type 1 Receptor Rationale and Design of the BLAST-AHF Study (Biased Ligand of the Angiotensin Receptor Study in Acute Heart Failure)
Heart Failure Therapeutics on the Basis of a Biased Ligand of the Angiotensin-2 Type 1 Receptor Rationale and Design of the BLAST-AHF Study (Biased Ligand of the Angiotensin Receptor Study in Acute Heart Failure)
复制标题
DOI：
10.1016/j.jchf.2014.09.008
复制
发表时间：
2015-03-01
影响因子：
13
通讯作者：
Pang, Peter S.
中科院分区：
文献类型：
--
作者：
Felker, G. Michael;Butler, Javed;Pang, Peter S.
BLAST-AHF（急性心力衰竭中血管紧张素受体的偏倚配体研究）研究旨在检测TRV 027（一种新型1型血管紧张素2受体的偏倚配体）在急性心力衰竭（AHF）患者中的疗效和安全性。AHF仍然是一个主要的公共卫生问题，目前没有可用的治疗方法已被证明是有利的影响结果。TRV 027是血管紧张素-2 1型受体的新型偏向配体，其拮抗血管紧张素刺激的G蛋白活化，同时刺激β-抑制蛋白。在动物模型中，这些作用减少后负荷，同时增加心脏性能和维持每搏输出量。在最初的人体研究中，TRV 027似乎主要在具有激活肾素-血管紧张素-醛固酮系统的患者中具有血流动力学活性，这是AHF治疗的潜在吸引力。BLAST-AHF是一项国际前瞻性、随机化、IIb期、剂量范围研究，将随机选择多达500名收缩压≥ 120 mm Hg的AHF患者，
The BLAST-AHF (Biased Ligand of the Angiotensin Receptor Study in Acute Heart Failure) study is designed to test the efficacy and safety of TRV027, a novel biased ligand of the angiotensin-2 type 1 receptor, in patients with acute heart failure (AHF). AHF remains a major public health problem, and no currently-available therapies have been shown to favorably affect outcomes. TRV027 is a novel biased ligand of the angiotensin-2 type 1 receptor that antagonizes angiotensin-stimulated G-protein activation while stimulating beta-arrestin. In animal models, these effects reduce afterload while increasing cardiac performance and maintaining stroke volume. In initial human studies, TRV027 appears to be hemodynamically active primarily in patients with activation of the renin-angiotensin-aldosterone system, a potentially attractive profile for an AHF therapeutic. BLAST-AHF is an international prospective, randomized, phase IIb, dose-ranging study that will randomize up to 500 AHF patients with systolic blood pressure >= 120 mm Hg and