{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T06:48:16Z","timestamp":1781765296427,"version":"3.54.5"},"reference-count":37,"publisher":"Public Library of Science (PLoS)","issue":"8","license":[{"start":{"date-parts":[[2024,8,19]],"date-time":"2024-08-19T00:00:00Z","timestamp":1724025600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Background<\/jats:title>\n<jats:p>Nearly half of patients with heart failure (HF) have preserved ejection fraction (EF) and the mortality and morbidity of patients with HF with preserved EF (HFpEF) are high. Patients with HFpEF are often elderly and their primary chronic symptom is severe exercise intolerance. Due to the frequent coexistence of hypertension in HFpEF patients, the use of anti-hypertensive medications is common in their treatment. While many cohort studies and several randomized controlled trials (RCTs) have examined the effectiveness of various anti-hypertensive drugs such as beta-blockers and renin-angiotensin system inhibitors in HFpEF, the role of calcium channel blockers (CCBs) remains uncertain. Despite several RCTs and cohort studies exploring the effects of CCBs on prognosis and exercise capacity in HFpEF patients, the findings have been inconsistent, likely due to limited statistical power and\/or variations in study design. Therefore, our aim is to conduct a systematic review and meta-analysis of studies on the effects of CCBs in these patients.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods<\/jats:title>\n<jats:p>This meta-analysis will include RCTs and cohort studies on the effect of CCBs in HFpEF patients. Information of studies will be collected from PubMed, Web of Science, and Scopus. The primary outcome of interest will be prognosis. The secondary outcome of interest will be exercise capacity.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Discussion<\/jats:title>\n<jats:p>Synthesizing our meta-analytical results with expert consensus could contribute to the formulation of updated clinical guidelines. Our systematic review and meta-analysis will provide directions for future research on the use of CCBs in HFpEF patients.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Systematic review registration<\/jats:title>\n<jats:p><jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/inplasy.com\/inplasy-2024-3-0097\" xlink:type=\"simple\">INPLASY202430097<\/jats:ext-link>.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0307258","type":"journal-article","created":{"date-parts":[[2024,8,19]],"date-time":"2024-08-19T17:57:23Z","timestamp":1724090243000},"page":"e0307258","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":3,"title":["Effects of calcium channel blockers in patients with heart failure with preserved ejection fraction: A protocol for systematic review and 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Heidenreich","year":"2022","journal-title":"Circulation"},{"key":"pone.0307258.ref011","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1002\/ejhf.442","article-title":"Spectrum of epidemiological and clinical findings in patients with heart failure with preserved ejection fraction stratified by study design: a systematic review","volume":"18","author":"M Vaduganathan","year":"2016","journal-title":"Eur J Heart Fail"},{"key":"pone.0307258.ref012","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1002\/ehf2.12204","article-title":"Renin-angiotensin blockade in heart failure with preserved ejection fraction: a systematic review and meta-analysis","volume":"4","author":"MS Khan","year":"2017","journal-title":"ESC Heart Fail"},{"key":"pone.0307258.ref013","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1007\/s10741-017-9637-0","article-title":"Effect of renin-angiotensin system inhibitors on mortality in heart failure with preserved ejection fraction: a meta-analysis of observational cohort and randomized controlled studies","volume":"22","author":"H Fukuta","year":"2017","journal-title":"Heart Fail Rev"},{"key":"pone.0307258.ref014","doi-asserted-by":"crossref","first-page":"1477","DOI":"10.1007\/s10741-020-09969-1","article-title":"Effect of renin-angiotensin system inhibition on cardiac structure and function and exercise capacity in heart failure with preserved ejection fraction: a meta-analysis of randomized controlled trials","volume":"26","author":"H Fukuta","year":"2021","journal-title":"Heart Fail Rev"},{"key":"pone.0307258.ref015","doi-asserted-by":"crossref","first-page":"e90555","DOI":"10.1371\/journal.pone.0090555","article-title":"Effects of beta-blockers on heart failure with preserved ejection fraction: a meta-analysis","volume":"9","author":"F Liu","year":"2014","journal-title":"PLoS One"},{"key":"pone.0307258.ref016","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1016\/j.ijcard.2016.11.239","article-title":"The effect of beta-blockers on mortality in heart failure with preserved ejection fraction: A meta-analysis of observational cohort and randomized controlled studies","volume":"228","author":"H Fukuta","year":"2017","journal-title":"Int J Cardiol"},{"key":"pone.0307258.ref017","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1007\/s10741-020-10013-5","article-title":"Effect of beta-blockers on heart failure severity in patients with heart failure with preserved ejection fraction: a meta-analysis of randomized controlled trials","volume":"26","author":"H Fukuta","year":"2021","journal-title":"Heart Fail Rev"},{"key":"pone.0307258.ref018","doi-asserted-by":"crossref","first-page":"981","DOI":"10.1016\/0002-9149(90)90937-V","article-title":"Usefulness of verapamil for congestive heart failure associated with abnormal left ventricular diastolic filling and normal left ventricular systolic performance","volume":"66","author":"JF Setaro","year":"1990","journal-title":"Am J Cardiol"},{"key":"pone.0307258.ref019","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1111\/j.1742-1241.2002.tb11193.x","article-title":"Effect of verapamil in elderly patients with left ventricular diastolic dysfunction as a cause of congestive heart failure","volume":"56","author":"MJ Hung","year":"2002","journal-title":"Int J Clin Pract"},{"key":"pone.0307258.ref020","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1161\/CIRCULATIONAHA.104.519876","article-title":"Statin therapy may be associated with lower mortality in patients with diastolic heart failure: a preliminary report","volume":"112","author":"H Fukuta","year":"2005","journal-title":"Circulation"},{"key":"pone.0307258.ref021","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1016\/j.ijcard.2013.12.008","article-title":"Prognostic factors of heart failure with preserved ejection fraction: a 12-year prospective cohort follow-up study","volume":"171","author":"CK Wu","year":"2014","journal-title":"Int J Cardiol"},{"key":"pone.0307258.ref022","doi-asserted-by":"crossref","first-page":"945","DOI":"10.1161\/CIRCHEARTFAILURE.114.001301","article-title":"Calcium channel blockers and outcomes in older patients with heart failure and preserved ejection fraction","volume":"7","author":"K Patel","year":"2014","journal-title":"Circ Heart Fail"},{"key":"pone.0307258.ref023","doi-asserted-by":"crossref","first-page":"1343","DOI":"10.1093\/eurjpc\/zwac004","article-title":"Associations between calcium channel blocker therapy and mortality in heart failure with preserved ejection fraction","volume":"29","author":"X Wang","year":"2022","journal-title":"Eur J Prev Cardiol"},{"key":"pone.0307258.ref024","doi-asserted-by":"crossref","first-page":"2202","DOI":"10.1002\/ejhf.3044","article-title":"Calcium channel blocker use and outcomes in patients with heart failure and mildly reduced and preserved ejection fraction","volume":"25","author":"S Matsumoto","year":"2023","journal-title":"Eur J Heart Fail"},{"key":"pone.0307258.ref025","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/2046-4053-4-1","article-title":"Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015 statement","volume":"4","author":"D Moher","year":"2015","journal-title":"Syst Rev"},{"key":"pone.0307258.ref026","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1164\/rccm.167.2.211","article-title":"American College of Chest P. ATS\/ACCP Statement on cardiopulmonary exercise testing","volume":"167","author":"S American Thoracic","year":"2003","journal-title":"Am J Respir Crit Care Med"},{"key":"pone.0307258.ref027","doi-asserted-by":"crossref","unstructured":"Laboratories ATSCoPSfCPF. ATS statement: guidelines for the six-minute walk test. Am J Respir Crit Care Med 2002; 166:111\u2013117.","DOI":"10.1164\/ajrccm.166.1.at1102"},{"key":"pone.0307258.ref028","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1016\/S0002-9149(77)80131-8","article-title":"New practical treadmill protocol for clinical use","volume":"39","author":"RA Wolthuis","year":"1977","journal-title":"Am J Cardiol"},{"key":"pone.0307258.ref029","doi-asserted-by":"crossref","first-page":"1017","DOI":"10.1016\/0002-8703(92)90986-6","article-title":"Assessment of patient outcome with the Minnesota Living with Heart Failure questionnaire: reliability and validity during a randomized, double-blind, placebo-controlled trial of pimobendan. Pimobendan Multicenter Research Group","volume":"124","author":"TS Rector","year":"1992","journal-title":"Am Heart J"},{"key":"pone.0307258.ref030","doi-asserted-by":"crossref","first-page":"1245","DOI":"10.1016\/S0735-1097(00)00531-3","article-title":"Development and evaluation of the Kansas City Cardiomyopathy Questionnaire: a new health status measure for heart failure","volume":"35","author":"CP Green","year":"2000","journal-title":"J Am Coll Cardiol"},{"key":"pone.0307258.ref031","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1056\/NEJM198203253061202","article-title":"Heart failure in outpatients: a randomized trial of digoxin versus placebo","volume":"306","author":"DC Lee","year":"1982","journal-title":"N Engl J Med"},{"key":"pone.0307258.ref032","doi-asserted-by":"crossref","first-page":"d5928","DOI":"10.1136\/bmj.d5928","article-title":"The Cochrane Collaboration\u2019s tool for assessing risk of bias in randomised trials","volume":"343","author":"JP Higgins","year":"2011","journal-title":"BMJ"},{"key":"pone.0307258.ref033","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1016\/j.jclinepi.2010.09.011","article-title":"GRADE guidelines: a new series of articles in the Journal of Clinical Epidemiology","volume":"64","author":"GH Guyatt","year":"2011","journal-title":"J Clin Epidemiol"},{"key":"pone.0307258.ref034","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1186\/s12874-021-01310-0","article-title":"Most published meta-regression analyses based on aggregate data suffer from methodological pitfalls: a meta-epidemiological study","volume":"21","author":"M Geissbuhler","year":"2021","journal-title":"BMC Med Res Methodol"},{"key":"pone.0307258.ref035","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1002\/clc.24058","article-title":"Association between the beta-blockers, calcium channel blockers, all-cause mortality and length of hospitalization in patients with heart failure with preserved ejection fraction: A meta-analysis of randomized controlled trials","volume":"46","author":"M Wu","year":"2023","journal-title":"Clin Cardiol"},{"issue":"Suppl 1","key":"pone.0307258.ref036","doi-asserted-by":"crossref","first-page":"17","DOI":"10.2165\/00129784-200707001-00003","article-title":"Calcium channel blockers: differences between subclasses","volume":"7","author":"WH Frishman","year":"2007","journal-title":"Am J Cardiovasc Drugs"},{"key":"pone.0307258.ref037","doi-asserted-by":"crossref","first-page":"1906","DOI":"10.1161\/CIRCRESAHA.122.320257","article-title":"Heart Failure With Preserved Ejection Fraction: Heterogeneous Syndrome, Diverse Preclinical Models","volume":"130","author":"J Roh","year":"2022","journal-title":"Circ Res"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0307258","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,8,19]],"date-time":"2024-08-19T17:57:36Z","timestamp":1724090256000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0307258"}},"subtitle":[],"editor":[{"given":"Yoshihiro","family":"Fukumoto","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2024,8,19]]},"references-count":37,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2024,8,19]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0307258","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,8,19]]}}}