{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,28]],"date-time":"2026-03-28T14:39:52Z","timestamp":1774708792288,"version":"3.50.1"},"reference-count":29,"publisher":"BMJ","issue":"9","license":[{"start":{"date-parts":[[2024,9,6]],"date-time":"2024-09-06T00:00:00Z","timestamp":1725580800000},"content-version":"unspecified","delay-in-days":5,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"the Shandong Province Science and Technology Research Program","award":["ZR2020MH038"],"award-info":[{"award-number":["ZR2020MH038"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81470558"],"award-info":[{"award-number":["81470558"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81700891"],"award-info":[{"award-number":["81700891"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2024,8,13]]},"published-print":{"date-parts":[[2024,9]]},"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Heart failure (HF) is a complex syndrome that affects millions of people worldwide and leads to significant morbidity and mortality. Sacubitril\/valsartan, a combination drug consisting of a neprilysin inhibitor and an angiotensin receptor blocker (ARB), has shown a greater improvement in the prognosis of HF than ACE inhibitors (ACEI) or ARB. Recent studies have found that ACEI\/ARB or sacubitril\/valsartan can increase flow-mediated dilation (FMD) and reduce pulse wave velocity (PWV), which are independent predictors of cardiovascular events and HF prognosis. The purpose of this study is to assess and compare the effect of sacubitril\/valsartan and ACEI\/ARB on FMD and PWV using meta-analysis and further provide a reference for the role of sacubitril\/valsartan in the treatment of HF.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and analysis<\/jats:title>\n                    <jats:p>Clinical randomised controlled trials investigating the effect of sacubitril\/valsartan and\/or ACEI\/ARB on FMD and PWV in patients with HF will be searched in the relevant database, including PubMed, Web of Science, Embase, Cochrane Library and China\u2019s National Knowledge Infrastructure up to January 2024. The outcomes of interest are changes in endothelial function assessed by FMD and changes in arterial stiffness assessed by PWV. The risk of bias was evaluated using the revised Cochrane risk of bias tool for randomised trials (RoB2.0). Review Manager V.5.3 software is used for meta-analysis data synthesis, sensitivity analysis, meta-regression analysis, subgroup analysis and risk of bias assessment. The reporting bias of studies will be evaluated using the funnel plot, in which symmetry will be assessed by Begg\u2019s and Egger\u2019s tests. The evidence quality of the included studies will be evaluated by the Grading of Recommendations Assessment, Development, and Evaluation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Ethics and dissemination<\/jats:title>\n                    <jats:p>This study only analyses research data from the published literature and therefore does not require ethical approval. We will submit the systematic review to a peer-reviewed journal.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>PROSPERO registration number<\/jats:title>\n                    <jats:p>CRD42024538148.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmjopen-2024-088744","type":"journal-article","created":{"date-parts":[[2024,9,11]],"date-time":"2024-09-11T01:54:28Z","timestamp":1726019668000},"page":"e088744","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":4,"title":["Comparative effects of sacubitril\/valsartan and ACEI\/ARB on endothelial function and arterial stiffness in patients with heart failure: a protocol for systematic review and meta-analysis"],"prefix":"10.1136","volume":"14","author":[{"given":"Zhiyong","family":"Ma","sequence":"first","affiliation":[{"name":"Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Department of Cardiology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhijie","family":"Fu","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, The First Affiliated Hospital of Shandong First Medical University, Jinan, Shandong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Na","family":"Li","sequence":"additional","affiliation":[{"name":"Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Department of Cardiology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shanying","family":"Huang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Department of Cardiology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1727-0125","authenticated-orcid":false,"given":"Lingyi","family":"Chi","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Qilu Hospital, Shandong University, Jinan, Shandong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[2024,9,10]]},"reference":[{"key":"2025121407402699000_14.9.e088744.1","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehab368"},{"key":"2025121407402699000_14.9.e088744.2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2021.12.012"},{"key":"2025121407402699000_14.9.e088744.3","first-page":"235","article-title":"Chinese guidelines for the diagnosis and treatment of heart failure 2024","volume":"52","year":"2024","journal-title":"Zhonghua Xin Xue Guan Bing Za Zhi"},{"key":"2025121407402699000_14.9.e088744.4","doi-asserted-by":"publisher","DOI":"10.1161\/CIR.0000000000000757"},{"key":"2025121407402699000_14.9.e088744.5","doi-asserted-by":"crossref","DOI":"10.3390\/biomedicines11030803","article-title":"Endothelial, Vascular and Sympathetic Alterations as Therapeutic Targets in Chronic Heart Failure","volume":"11","author":"Quarti-Trevano","year":"2023","journal-title":"Biomedicines"},{"key":"2025121407402699000_14.9.e088744.6","article-title":"Endothelial Dysfunction and Heart Failure with Preserved Ejection Fraction-An Updated Review of the Literature","volume":"14","author":"De Luca","year":"2023","journal-title":"Life (Basel)"},{"key":"2025121407402699000_14.9.e088744.7","doi-asserted-by":"crossref","DOI":"10.1007\/s00395-022-00909-8","article-title":"Coronary blood flow in heart failure: cause, consequence and bystander","volume":"117","author":"Heusch","year":"2022","journal-title":"Basic Res Cardiol"},{"key":"2025121407402699000_14.9.e088744.8","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1007\/s11897-023-00602-4","article-title":"The Role of the Vasculature in Heart Failure","volume":"20","author":"Joshi","year":"2023","journal-title":"Curr Heart Fail Rep"},{"key":"2025121407402699000_14.9.e088744.9","doi-asserted-by":"crossref","DOI":"10.3390\/jcm11123507","article-title":"The Analysis of Arterial Stiffness in Heart Failure Patients: The Prognostic Role of Pulse Wave Velocity, Augmentation Index and Stiffness Index","volume":"11","author":"Anastasio","year":"2022","journal-title":"J Clin Med"},{"key":"2025121407402699000_14.9.e088744.10","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehz350"},{"key":"2025121407402699000_14.9.e088744.11","doi-asserted-by":"crossref","DOI":"10.1161\/JAHA.115.002270","article-title":"Prognostic Value of Flow-Mediated Vasodilation in Brachial Artery and Fingertip Artery for Cardiovascular Events: A Systematic Review and Meta-Analysis","volume":"4","author":"Matsuzawa","year":"2015","journal-title":"J Am Heart Assoc"},{"key":"2025121407402699000_14.9.e088744.12","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2009.10.061"},{"key":"2025121407402699000_14.9.e088744.13","first-page":"617","article-title":"Carotid-Femoral Pulse Wave Velocity in the Prediction of Cardiovascular Events and Mortality: An Updated Systematic Review and Meta-Analysis","volume":"69","author":"Zhong","year":"2018","journal-title":"Angiol Open Access"},{"key":"2025121407402699000_14.9.e088744.14","doi-asserted-by":"crossref","DOI":"10.3390\/ijms25074035","article-title":"Renin-Angiotensin-Aldosterone System: From History to Practice of a Secular Topic","volume":"25","author":"Ksiazek","year":"2024","journal-title":"Int J Mol Sci"},{"key":"2025121407402699000_14.9.e088744.15","doi-asserted-by":"crossref","first-page":"102411","DOI":"10.1016\/j.cpcardiol.2024.102411","article-title":"Unraveling the complex pathophysiology of heart failure: insights into the role of renin-angiotensin-aldosterone system (RAAS) and sympathetic nervous system (SNS)","volume":"49","author":"Varghese","year":"2024","journal-title":"Curr Probl Cardiol"},{"key":"2025121407402699000_14.9.e088744.16","article-title":"Comparison of Outcomes Between Sacubitril\/Valsartan and Enalapril in Patients With Heart Failure: A Systematic Review and Meta-Analysis","volume":"15","author":"Reyaz","year":"2023","journal-title":"Cureus"},{"key":"2025121407402699000_14.9.e088744.17","article-title":"Influence of Ejection Fraction on Outcomes and Efficacy of Sacubitril\/Valsartan (LCZ696) in Heart Failure with Reduced Ejection Fraction","volume":"9","author":"Solomon","year":"2016","journal-title":"Circ: Heart Failure"},{"key":"2025121407402699000_14.9.e088744.18","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1001\/jamacardio.2023.0065","article-title":"Effect of Sacubitril\/Valsartan vs Valsartan on Left Atrial Volume in Patients With Pre-Heart Failure With Preserved Ejection Fraction: The PARABLE Randomized Clinical Trial","volume":"8","author":"Ledwidge","year":"2023","journal-title":"JAMA Cardiol"},{"key":"2025121407402699000_14.9.e088744.19","doi-asserted-by":"crossref","first-page":"102464","DOI":"10.1016\/j.cpcardiol.2024.102464","article-title":"Impact of angiotensin receptor-neprilysin inhibition (ARNI) in improving ejection fraction and left and right ventricular remodeling in heart failure","volume":"49","author":"Bhushan","year":"2024","journal-title":"Curr Probl Cardiol"},{"key":"2025121407402699000_14.9.e088744.20","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1024\/0301-1526\/a000971","article-title":"Effect of ACEI and ARB treatment on nitric oxide-dependent endothelial function","volume":"50","author":"Li","year":"2021","journal-title":"Vasa"},{"key":"2025121407402699000_14.9.e088744.21","doi-asserted-by":"crossref","first-page":"425","DOI":"10.3233\/CH-201032","article-title":"Effect of sacubitril valsartan on cardiac function and endothelial function in patients with chronic heart failure with reduced ejection fraction","volume":"77","author":"Li","year":"2021","journal-title":"Clin Hemorheol Microcirc"},{"key":"2025121407402699000_14.9.e088744.22","doi-asserted-by":"crossref","DOI":"10.3389\/fphar.2022.1069828","article-title":"Short-term effect of sacubitril\/valsartan on endothelial dysfunction and arterial stiffness in patients with chronic heart failure","volume":"13","author":"Cassano","year":"2022","journal-title":"Front Pharmacol"},{"key":"2025121407402699000_14.9.e088744.23","doi-asserted-by":"crossref","DOI":"10.1155\/2022\/2432567","article-title":"Comparative Efficacy of Antihypertensive Agents in Flow-Mediated Vasodilation of Patients with Hypertension: Network Meta-Analysis of Randomized Controlled Trial","volume":"2022","author":"Ding","year":"2022","journal-title":"Int J Hypertens"},{"key":"2025121407402699000_14.9.e088744.24","doi-asserted-by":"crossref","DOI":"10.3389\/fphar.2023.1225795","article-title":"Comparative effect of antihypertensive drugs in improving arterial stiffness in adults with hypertension (RIGIPREV study). A network meta-analysis","volume":"14","author":"Cavero-Redondo","year":"2023","journal-title":"Front Pharmacol"},{"key":"2025121407402699000_14.9.e088744.25","doi-asserted-by":"crossref","DOI":"10.1136\/bmj.g7647","article-title":"Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015: elaboration and explanation","volume":"350","author":"Shamseer","year":"2015","journal-title":"BMJ"},{"key":"2025121407402699000_14.9.e088744.26","doi-asserted-by":"crossref","DOI":"10.1136\/bmj.d5928","article-title":"The Cochrane Collaboration\u2019s tool for assessing risk of bias in randomised trials","volume":"343","author":"Higgins","year":"2011","journal-title":"BMJ"},{"key":"2025121407402699000_14.9.e088744.27","doi-asserted-by":"crossref","DOI":"10.1136\/bmjopen-2018-028771","article-title":"Effect of Baduanjin exercise on patients with chronic heart failure: protocol for a systematic review and meta-analysis","volume":"9","author":"Li","year":"2019","journal-title":"BMJ Open"},{"key":"2025121407402699000_14.9.e088744.28","doi-asserted-by":"publisher","DOI":"10.1111\/jebm.12141"},{"key":"2025121407402699000_14.9.e088744.29","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.39489.470347.AD"}],"container-title":["BMJ Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/bmjopen-2024-088744","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,14]],"date-time":"2025-12-14T15:40:37Z","timestamp":1765726837000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmjopen.bmj.com\/lookup\/doi\/10.1136\/bmjopen-2024-088744"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,9]]},"references-count":29,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2024,9,10]]},"published-print":{"date-parts":[[2024,9]]}},"alternative-id":["10.1136\/bmjopen-2024-088744"],"URL":"https:\/\/doi.org\/10.1136\/bmjopen-2024-088744","relation":{},"ISSN":["2044-6055","2044-6055"],"issn-type":[{"value":"2044-6055","type":"print"},{"value":"2044-6055","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,9]]}}}