Sacubitril/valsartan versus valsartan in regressing myocardial fibrosis in hypertension: a prospective, randomized, open-label, blinded endpoint clinical trial protocol
BackgroundDiffuse interstitial myocardial fibrosis is a key common pathological manifestation in hypertensive heart disease (HHD) progressing to heart failure (HF). Angiotensin receptor–neprilysin inhibitors (ARNi), now a front-line treatment for HF, confer benefits independent of blood pressure, si...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-08-01
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| Series: | Frontiers in Cardiovascular Medicine |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcvm.2023.1248468/full |
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| author | Vivian Lee Qishi Zheng Desiree-Faye Toh Chee Jian Pua Jennifer A. Bryant Chi-Hang Lee Stuart A. Cook Stuart A. Cook Stuart A. Cook Javed Butler Javed Butler Javier Díez Javier Díez A. Mark Richards A. Mark Richards Thu-Thao Le Thu-Thao Le Calvin W. L. Chin Calvin W. L. Chin Calvin W. L. Chin |
| author_facet | Vivian Lee Qishi Zheng Desiree-Faye Toh Chee Jian Pua Jennifer A. Bryant Chi-Hang Lee Stuart A. Cook Stuart A. Cook Stuart A. Cook Javed Butler Javed Butler Javier Díez Javier Díez A. Mark Richards A. Mark Richards Thu-Thao Le Thu-Thao Le Calvin W. L. Chin Calvin W. L. Chin Calvin W. L. Chin |
| author_sort | Vivian Lee |
| collection | DOAJ |
| description | BackgroundDiffuse interstitial myocardial fibrosis is a key common pathological manifestation in hypertensive heart disease (HHD) progressing to heart failure (HF). Angiotensin receptor–neprilysin inhibitors (ARNi), now a front-line treatment for HF, confer benefits independent of blood pressure, signifying a multifactorial mode of action beyond hemodynamic regulation. We aim to test the hypothesis that compared with angiotensin II receptor blockade (ARB) alone, ARNi is more effective in regressing diffuse interstitial myocardial fibrosis in HHD.MethodsRole of ARNi in Ventricular Remodeling in Hypertensive LVH (REVERSE-LVH) is a prospective, randomized, open-label, blinded endpoint (PROBE) clinical trial. Adults with hypertension and left ventricular hypertrophy (LVH) according to Asian sex- and age-specific thresholds on cardiovascular magnetic resonance (CMR) imaging are randomized to treatment with either sacubitril/valsartan (an ARNi) or valsartan (an ARB) in 1:1 ratio for a duration of 52 weeks, at the end of which a repeat CMR is performed to assess differential changes from baseline between the two groups. The primary endpoint is the change in CMR-derived diffuse interstitial fibrosis volume. Secondary endpoints include changes in CMR-derived left ventricular mass, volumes, and functional parameters. Serum samples are collected and stored to assess the effects of ARNi, compared with ARB, on circulating biomarkers of cardiac remodeling. The endpoints will be analyzed with reference to the corresponding baseline parameters to evaluate the therapeutic effect of sacubitril/valsartan vs. valsartan.DiscussionREVERSE-LVH will examine the anti-fibrotic potential of sacubitril/valsartan and will offer mechanistic insights into the clinical benefits of sacubitril/valsartan in hypertension in relation to cardiac remodeling. Advancing the knowledge of the pathophysiology of HHD will consolidate effective risk stratification and personalized treatment through a multimodal manner integrating complementary CMR and biomarkers into the conventional care approach.Clinical Trial Registration: ClinicalTrials.gov, identifier, NCT03553810. |
| first_indexed | 2024-03-12T13:56:34Z |
| format | Article |
| id | doaj.art-1b177e2affe24770b9f07cf919337730 |
| institution | Directory Open Access Journal |
| issn | 2297-055X |
| language | English |
| last_indexed | 2024-03-12T13:56:34Z |
| publishDate | 2023-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cardiovascular Medicine |
| spelling | doaj.art-1b177e2affe24770b9f07cf9193377302023-08-22T13:55:09ZengFrontiers Media S.A.Frontiers in Cardiovascular Medicine2297-055X2023-08-011010.3389/fcvm.2023.12484681248468Sacubitril/valsartan versus valsartan in regressing myocardial fibrosis in hypertension: a prospective, randomized, open-label, blinded endpoint clinical trial protocolVivian Lee0Qishi Zheng1Desiree-Faye Toh2Chee Jian Pua3Jennifer A. Bryant4Chi-Hang Lee5Stuart A. Cook6Stuart A. Cook7Stuart A. Cook8Javed Butler9Javed Butler10Javier Díez11Javier Díez12A. Mark Richards13A. Mark Richards14Thu-Thao Le15Thu-Thao Le16Calvin W. L. Chin17Calvin W. L. Chin18Calvin W. L. Chin19National Heart Research Institute Singapore (NHRIS), National Heart Centre Singapore, Singapore, SingaporeCochrane Singapore, Singapore, SingaporeNational Heart Research Institute Singapore (NHRIS), National Heart Centre Singapore, Singapore, SingaporeNational Heart Research Institute Singapore (NHRIS), National Heart Centre Singapore, Singapore, SingaporeDepartment of Cardiology, National Heart Centre Singapore, Singapore, SingaporeDepartment of Cardiology, National University Heart Centre Singapore, Singapore, SingaporeNational Heart Research Institute Singapore (NHRIS), National Heart Centre Singapore, Singapore, SingaporeDepartment of Cardiology, National Heart Centre Singapore, Singapore, SingaporeCardiovascular & Metabolic Disorders Program, Duke-NUS Medical School, Singapore, SingaporeBaylor Scott and White Research Institute, Dallas, TX, United StatesDepartment of Medicine, University of Mississippi School of Medicine, Jackson, MS, United StatesCentre for Applied Medical Research (CIMA), and School of Medicine, University of Navarra, Pamplona, SpainCenter for Network Biomedical Research of Cardiovascular Diseases (CIBERCV), Carlos III Institute of Health, Madrid, Spain0Cardiovascular Research Institute, National University Heart Centre, Singapore, Singapore1Christchurch Heart Institute, University of Otago, Christchurch, New ZealandNational Heart Research Institute Singapore (NHRIS), National Heart Centre Singapore, Singapore, Singapore2Cardiovascular Academic Clinical Program (ACP), Duke-NUS Medical School, Singapore, SingaporeNational Heart Research Institute Singapore (NHRIS), National Heart Centre Singapore, Singapore, SingaporeDepartment of Cardiology, National Heart Centre Singapore, Singapore, Singapore2Cardiovascular Academic Clinical Program (ACP), Duke-NUS Medical School, Singapore, SingaporeBackgroundDiffuse interstitial myocardial fibrosis is a key common pathological manifestation in hypertensive heart disease (HHD) progressing to heart failure (HF). Angiotensin receptor–neprilysin inhibitors (ARNi), now a front-line treatment for HF, confer benefits independent of blood pressure, signifying a multifactorial mode of action beyond hemodynamic regulation. We aim to test the hypothesis that compared with angiotensin II receptor blockade (ARB) alone, ARNi is more effective in regressing diffuse interstitial myocardial fibrosis in HHD.MethodsRole of ARNi in Ventricular Remodeling in Hypertensive LVH (REVERSE-LVH) is a prospective, randomized, open-label, blinded endpoint (PROBE) clinical trial. Adults with hypertension and left ventricular hypertrophy (LVH) according to Asian sex- and age-specific thresholds on cardiovascular magnetic resonance (CMR) imaging are randomized to treatment with either sacubitril/valsartan (an ARNi) or valsartan (an ARB) in 1:1 ratio for a duration of 52 weeks, at the end of which a repeat CMR is performed to assess differential changes from baseline between the two groups. The primary endpoint is the change in CMR-derived diffuse interstitial fibrosis volume. Secondary endpoints include changes in CMR-derived left ventricular mass, volumes, and functional parameters. Serum samples are collected and stored to assess the effects of ARNi, compared with ARB, on circulating biomarkers of cardiac remodeling. The endpoints will be analyzed with reference to the corresponding baseline parameters to evaluate the therapeutic effect of sacubitril/valsartan vs. valsartan.DiscussionREVERSE-LVH will examine the anti-fibrotic potential of sacubitril/valsartan and will offer mechanistic insights into the clinical benefits of sacubitril/valsartan in hypertension in relation to cardiac remodeling. Advancing the knowledge of the pathophysiology of HHD will consolidate effective risk stratification and personalized treatment through a multimodal manner integrating complementary CMR and biomarkers into the conventional care approach.Clinical Trial Registration: ClinicalTrials.gov, identifier, NCT03553810.https://www.frontiersin.org/articles/10.3389/fcvm.2023.1248468/fullmyocardial fibrosissacubitril/valsartanARNihypertensive heart diseaseheart failurecardiovascular magnetic resonance imaging |
| spellingShingle | Vivian Lee Qishi Zheng Desiree-Faye Toh Chee Jian Pua Jennifer A. Bryant Chi-Hang Lee Stuart A. Cook Stuart A. Cook Stuart A. Cook Javed Butler Javed Butler Javier Díez Javier Díez A. Mark Richards A. Mark Richards Thu-Thao Le Thu-Thao Le Calvin W. L. Chin Calvin W. L. Chin Calvin W. L. Chin Sacubitril/valsartan versus valsartan in regressing myocardial fibrosis in hypertension: a prospective, randomized, open-label, blinded endpoint clinical trial protocol Frontiers in Cardiovascular Medicine myocardial fibrosis sacubitril/valsartan ARNi hypertensive heart disease heart failure cardiovascular magnetic resonance imaging |
| title | Sacubitril/valsartan versus valsartan in regressing myocardial fibrosis in hypertension: a prospective, randomized, open-label, blinded endpoint clinical trial protocol |
| title_full | Sacubitril/valsartan versus valsartan in regressing myocardial fibrosis in hypertension: a prospective, randomized, open-label, blinded endpoint clinical trial protocol |
| title_fullStr | Sacubitril/valsartan versus valsartan in regressing myocardial fibrosis in hypertension: a prospective, randomized, open-label, blinded endpoint clinical trial protocol |
| title_full_unstemmed | Sacubitril/valsartan versus valsartan in regressing myocardial fibrosis in hypertension: a prospective, randomized, open-label, blinded endpoint clinical trial protocol |
| title_short | Sacubitril/valsartan versus valsartan in regressing myocardial fibrosis in hypertension: a prospective, randomized, open-label, blinded endpoint clinical trial protocol |
| title_sort | sacubitril valsartan versus valsartan in regressing myocardial fibrosis in hypertension a prospective randomized open label blinded endpoint clinical trial protocol |
| topic | myocardial fibrosis sacubitril/valsartan ARNi hypertensive heart disease heart failure cardiovascular magnetic resonance imaging |
| url | https://www.frontiersin.org/articles/10.3389/fcvm.2023.1248468/full |
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