Antisense inhibition of angiotensinogen with IONIS-AGT-LRx: Results of Phase 1 and Phase 2 studies

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

Highlights • Targeting AGT is a novel approach to inhibit the RAAS pathway. • AGT is primarily synthesized in the liver. • IONIS-AGT-LRx is an ASO directed to hepatocyte-derived AGT. • In 2 phase 2 trials as monotherapy and as an add-on to 2 to 3 medications for hypertension, IONIS-AGT-LRx was well tolerated with a significant reduction in plasma AGT levels. • IONIS-AGT-LRx is being developed for hypertension and heart failure indications.

Related collections

Most cited references 37

Record: found
Abstract: found
Article: not found

Effects of an Angiotensin-Converting–Enzyme Inhibitor, Ramipril, on Cardiovascular Events in High-Risk Patients

S Yusuf, P Sleight, J Pogue … (2000)

Angiotensin-converting-enzyme inhibitors improve the outcome among patients with left ventricular dysfunction, whether or not they have heart failure. We assessed the role of an angiotensin-converting-enzyme inhibitor, ramipril, in patients who were at high risk for cardiovascular events but who did not have left ventricular dysfunction or heart failure. A total of 9297 high-risk patients (55 years of age or older) who had evidence of vascular disease or diabetes plus one other cardiovascular risk factor and who were not known to have a low ejection fraction or heart failure were randomly assigned to receive ramipril (10 mg once per day orally) or matching placebo for a mean of five years. The primary outcome was a composite of myocardial infarction, stroke, or death from cardiovascular causes. The trial was a two-by-two factorial study evaluating both ramipril and vitamin E. The effects of vitamin E are reported in a companion paper. A total of 651 patients who were assigned to receive ramipril (14.0 percent) reached the primary end point, as compared with 826 patients who were assigned to receive placebo (17.8 percent) (relative risk, 0.78; 95 percent confidence interval, 0.70 to 0.86; P<0.001). Treatment with ramipril reduced the rates of death from cardiovascular causes (6.1 percent, as compared with 8.1 percent in the placebo group; relative risk, 0.74; P<0.001), myocardial infarction (9.9 percent vs. 12.3 percent; relative risk, 0.80; P<0.001), stroke (3.4 percent vs. 4.9 percent; relative risk, 0.68; P<0.001), death from any cause (10.4 percent vs. 12.2 percent; relative risk, 0.84; P=0.005), revascularization procedures (16.3 percent vs. 18.8 percent; relative risk, 0.85; P<0.001), cardiac arrest (0.8 percent vs. 1.3 percent; relative risk, 0.62; P=0.02), [corrected] heart failure (9.1 percent vs. 11.6 percent; relative risk, 0.77; P<0.001), and complications related to diabetes (6.4 percent vs. 7.6 percent; relative risk, 0.84; P=0.03). Ramipril significantly reduces the rates of death, myocardial infarction, and stroke in a broad range of high-risk patients who are not known to have a low ejection fraction or heart failure.

0 comments Cited 274 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: not found
Article: not found

RNA-Targeted Therapeutics

Stanley Crooke, Brenda Baker, C Frank Bennett … (2018)

0 comments Cited 266 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Lipoprotein(a) Reduction in Persons with Cardiovascular Disease

Sotirios Tsimikas, Ewa Karwatowska-Prokopczuk, Ioanna Gouni-Berthold … (2020)

Lipoprotein(a) levels are genetically determined and, when elevated, are a risk factor for cardiovascular disease and aortic stenosis. There are no approved pharmacologic therapies to lower lipoprotein(a) levels.