Changes in mid‐regional pro‐adrenomedullin during treatment with sacubitril/valsartan

Author:

Myhre Peder L.1,Liu Yuxi2,Kulac Ian J.3,Claggett Brian L.3,Prescott Margaret F.4,Felker G. Michael5,Butler Javed67,Piña Ileana L.8,Rouleau Jean L.9,Zile Michael R.10,McMurray John J.V.11,Ward Jonathan H.4,Solomon Scott D.3,Januzzi James L.212

Affiliation:

1. Division of Medicine Akershus University Hospital and K.G. Jebsen Center for Cardiac Biomarkers, University of Oslo Oslo Norway

2. Cardiology Division Massachusetts General Hospital, Harvard Medical School Boston MA USA

3. Cardiovascular Division Brigham and Women's Hospital Boston MA USA

4. Novartis Pharmaceutical Corporation East Hanover NJ USA

5. Duke University Medical School and Duke Clinical Research Institute Durham NC USA

6. University of Mississippi Medical School Jackson MS USA

7. Baylor Scott and White Research Institute Dallas TX USA

8. Thomas Jefferson University Philadelphia PA USA

9. Montreal Heart Institute and University of Montreal Montreal Quebec Canada

10. Medical University of South Carolina and Ralph H. Johnson Veterans Administration Medical Center Charleston SC USA

11. University of Glasgow Glasgow UK

12. Baim Institute for Clinical Research Boston MA USA

Abstract

ABSTRACTAimsAdrenomedullin is a vasodilatory peptide with a role in microcirculatory and endothelial homeostasis. Adrenomedullin is a substrate for neprilysin and may therefore play a role in beneficial effects of sacubitril/valsartan (Sac/Val) treatment.Methods and resultsMid‐regional pro‐adrenomedullin (MR‐proADM) was measured in 156 patients with heart failure with reduced ejection fraction (HFrEF) treated with Sac/Val and 264 patients with heart failure with preserved ejection fraction (HFpEF) randomized to treatment with Sac/Val or valsartan. Echocardiography and Kansas City Cardiomyopathy Questionnaire results were collected at baseline and after 6 and 12 months in the HFrEF cohort. Median (Q1–Q3) baseline MR‐proADM concentrations were 0.80 (0.59–0.99) nmol/L in HFrEF and 0.88 (0.68–1.20) nmol/L in HFpEF. After 12 weeks of treatment with Sac/Val, MR‐proADM increased by median 49% in HFrEF and 60% in HFpEF, while there were no significant changes in valsartan‐treated patients (median 2%). Greater increases in MR‐proADM were associated with higher Sac/Val doses. Changes in MR‐proADM correlated weakly with changes in N‐terminal pro‐B‐type natriuretic peptide, cardiac troponin T and urinary cyclic guanosine monophosphate. Increases in MR‐proADM were associated with decreases in blood pressure, but not significantly associated with changes in echocardiographic parameters or health status.ConclusionsMR‐proAD concentrations rise substantially following treatment with Sac/Val, in contrast to no change from valsartan. Change in MR‐proADM from neprilysin inhibition did not correlate with improvements in cardiac structure and function or health status. More data are needed regarding the role of adrenomedullin and its related peptides in the treatment of heart failure.Clinical Trial Registration: PROVE‐HF ClinicalTrials.gov Identifier: NCT02887183, PARAMOUNT ClinicalTrials.gov Identifier: NCT00887588.

Funder

Novartis Pharmaceuticals Corporation

Publisher

Wiley

Subject

Cardiology and Cardiovascular Medicine

Cited by 3 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3