{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T04:01:14Z","timestamp":1792123274259,"version":"4.4.0"},"reference-count":38,"publisher":"BMJ","issue":"2","license":[{"start":{"date-parts":[[2020,8,20]],"date-time":"2020-08-20T00:00:00Z","timestamp":1597881600000},"content-version":"unspecified","delay-in-days":19,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["Open Heart"],"accepted":{"date-parts":[[2020,7,13]]},"published-print":{"date-parts":[[2020,8]]},"abstract":"<jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>To systematically review evidence comparing the effect of low-dose versus high-dose ACE inhibitors (ACEIs) on all-cause and cardiovascular mortality and hospitalisation, functional capacity and side effects in patients with heart failure (HF).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We searched PubMed, Embase, Cochrane CENTRAL and LILACS up to January 2019. We included randomised controlled trials (RCTs) comparing low-dose versus high-dose ACEIs in adults with HF with reduced left ventricular ejection fraction (HFrEF). Study selection and data extraction were performed by two independent reviewers. Risk of bias was assessed with RoB 2.0, and quality of evidence with Grading of Recommendations Assessment, Development and Evaluation (GRADE). We conducted random effects meta-analysis and trial sequential analysis.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>We included eight RCTs (5829 patients with HF). In comparison with low-dose ACEIs, high-dose ACEIs showed a non-significant effect on all-cause mortality (8 RCTs, n=5828, relative risk (RR) 0.95, 95% CI 0.88 to 1.02; moderate quality of evidence), cardiovascular mortality (6 RCTs, n=4048, RR 0.93, 95%\u2009CI 0.85 to 1.01; moderate quality of evidence), all-cause hospitalisation (5 RCTs, n=5394, RR 0.95, 95%\u2009CI 0.82 to 1.10; moderate quality of evidence) and cardiovascular hospitalisation (4 RCTs, n=5242, RR 0.98, 95%\u2009CI 0.83 to 1.17; low quality of evidence). High-dose ACEI increased functional capacity (4 studies, n=555, standardised mean difference 0.38, 95%\u2009CI 0.20 to 0.55; low quality of evidence) and the risk of hypotension (4 RCTs, n=3783, RR 1.64, 95%\u2009CI 1.30 to 2.05; moderate quality of evidence). High-dose ACEI had no effect on dizziness (3 RCTs, n=4994, RR 1.37, 95%\u2009CI 0.97 to 1.93; low quality of evidence), but decreased the risk of cough (4 RCTs, n=5146, RR 0.85, 95%\u2009CI 0.73 to 0.98; moderate quality of evidence).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>The magnitude of benefit of using high dose versus low to intermediate doses of ACEIs might be less than traditionally suggested in clinical guidelines. These findings might help clinicians address the complex task of HF management in a more rational and timely fashion, saving efforts to implement strategies with the greatest net clinical benefit.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/openhrt-2019-001228","type":"journal-article","created":{"date-parts":[[2020,8,21]],"date-time":"2020-08-21T01:20:15Z","timestamp":1597972815000},"page":"e001228","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":6,"title":["High-dose versus low-dose angiotensin converting enzyme inhibitors in heart failure: systematic review and meta-analysis"],"prefix":"10.1136","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1389-2311","authenticated-orcid":false,"given":"Celina Borges","family":"Migliavaca","sequence":"first","affiliation":[{"name":"Institute for Education and Research, Hospital Moinhos de Vento (HMV), Porto Alegre, RS, Brazil"},{"name":"Programa de P\u00f3s-Gradua\u00e7\u00e3o em Epidemiologia, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1833-8221","authenticated-orcid":false,"given":"Cinara","family":"Stein","sequence":"additional","affiliation":[{"name":"Institute for Education and Research, Hospital Moinhos de Vento (HMV), Porto Alegre, RS, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7908-4213","authenticated-orcid":false,"given":"Ver\u00f4nica","family":"Colpani","sequence":"additional","affiliation":[{"name":"Institute for Education and Research, Hospital Moinhos de Vento (HMV), Porto Alegre, RS, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruna","family":"Eibel","sequence":"additional","affiliation":[{"name":"Post Graduate Program in Health Sciences: Cardiology, Instituto de Cardiologia\/Funda\u00e7\u00e3o Universit\u00e1ria de Cardiologia (IC\/FUC), Porto Alegre, RS, Brazil"},{"name":"Fisioterapia, Centro Universit\u00e1rio da Serra Ga\u00facha, Caxias do Sul, RS, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberta","family":"Bgeginski","sequence":"additional","affiliation":[{"name":"School of Kinesiology, Faculty of Health Sciences, University of Western Ontario, London, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcus Vinicius","family":"Sim\u00f5es","sequence":"additional","affiliation":[{"name":"Cardiology Division, Universidade de S\u00e3o Paulo (USP), Ribeir\u00e3o Preto, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luiz Eduardo","family":"Rohde","sequence":"additional","affiliation":[{"name":"Cardiovascular Division, Hospital de Cl\u00ednicas de Porto Alegre (HCPA), Porto Alegre, RS, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2637-6837","authenticated-orcid":false,"given":"Maicon","family":"Falavigna","sequence":"additional","affiliation":[{"name":"Institute for Education and Research, Hospital Moinhos de Vento (HMV), Porto Alegre, RS, Brazil"},{"name":"Programa de P\u00f3s-Gradua\u00e7\u00e3o em Epidemiologia, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2020,8,20]]},"reference":[{"key":"2025081709535340000_7.2.e001228.1","doi-asserted-by":"crossref","first-page":"17058","DOI":"10.1038\/nrdp.2017.58","article-title":"Heart failure with reduced ejection fraction","volume":"3","author":"Bloom","year":"2017","journal-title":"Nat Rev Dis Primers"},{"key":"2025081709535340000_7.2.e001228.2","doi-asserted-by":"publisher","DOI":"10.1002\/ejhf.483"},{"key":"2025081709535340000_7.2.e001228.3","doi-asserted-by":"publisher","DOI":"10.15420\/cfr.2016:25:2"},{"key":"2025081709535340000_7.2.e001228.4","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehw128"},{"key":"2025081709535340000_7.2.e001228.5","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2013.05.019"},{"key":"2025081709535340000_7.2.e001228.6","first-page":"1342","article-title":"2017 comprehensive update of the Canadian cardiovascular Society guidelines for the management of heart failure","volume":"33","author":"Ezekowitz","year":"2017","journal-title":"Can J Cardiol"},{"key":"2025081709535340000_7.2.e001228.7","unstructured":"Scottish Intercollegiate Guidelines Network (SIGN) . 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