Antisense Inhibition of Angiotensinogen With IONIS-AGT-LRx

被引：60

作者：

Morgan, Erin S. ^{[1
]}

Tami, Yvonne ^{[1
]}

Hu, Kuolung ^{[1
]}

Brambatti, Michela ^{[1
]}

Mullick, Adam E. ^{[1
]}

Geary, Richard S. ^{[1
]}

Bakris, George L. ^{[2
]}

Tsimikas, Sotirios ^{[1
,3
]}

机构：

[1] Ionis Pharmaceut, Carlsbad, CA USA

[2] Univ Chicago Med, Dept Med, Chicago, IL USA

[3] Univ Calif San Diego, Dept Med, Div Cardiovasc Med, La Jolla, CA 92093 USA

来源：

JACC-BASIC TO TRANSLATIONAL SCIENCE | 2021年 / 6卷 / 06期

关键词：

angiotensinogen; antisense; hepatocyte; hypertension; oligonucleotide; RAAS; CHRONIC HEART-FAILURE; TARGETED DELIVERY; BLOOD-PRESSURE; END-POINTS; HYPERTENSION; OLIGONUCLEOTIDES; ALDOSTERONE; MORTALITY; ALISKIREN; SYSTEM;

D O I：

10.1016/j.jacbts.2021.04.004

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Targeting angiotensinogen (AGT) may provide a novel approach to more optimally inhibit the renin-angiotensin-aldosterone system pathway. Double-blind, placebo-controlled clinical trials were performed in subjects with hypertension as monotherapy or as an add-on to angiotensin-converting enzyme inhibitors/angiotensin receptor blockers with IONIS-AGT-L-Rx mc versus placebo up to 2 months. IONIS-AGT-L-Rx was well tolerated with no significant changes in platelet count, potassium levels, or liver and renal function. IONIS-AGT-L-Rx significantly reduced AGT levels compared with placebo in all 3 studies. Although not powered for this endpoint, trends were noted in blood pressure reduction. In conclusion, IONIS-AGT-L-Rx significantly reduces AGT with a favorable safety, tolerability, and on-target profile. (C) 2021 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation.

引用

收藏

页码：485 / 496

页数：12

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