{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T17:50:03Z","timestamp":1789753803794,"version":"4.0.1"},"reference-count":18,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2018,6,19]],"date-time":"2018-06-19T00:00:00Z","timestamp":1529366400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"},{"start":{"date-parts":[[2018,6,19]],"date-time":"2018-06-19T00:00:00Z","timestamp":1529366400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100011725","name":"Les Laboratoires Servier","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100011725","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Les Laboratoires Servier (Suresnes, France)"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2018,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>A network meta-analysis (NMA) of all recommended drug groups for the treatment of heart failure with reduced ejection fraction (HFrEF), including their combinations, was performed to assess the relative efficacy and incremental benefit.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>A search was made in biomedical databases for randomized controlled trials published between 1987 and 2017 on angiotensin-converting enzyme inhibitors (ACEIs), beta-blockers (BBs), angiotensin receptor blockers (ARBs), mineralocorticoid receptor antagonists (MRAs), ivabradine (IVA), or angiotensin receptor\u2013neprilysin inhibitors (ARNI). A total of 58 relevant trials were identified. The relative efficacy of each treatment group (or combination) in terms of all-cause mortality, cardiovascular mortality, all-cause hospitalizations and hospitalizations for heart failure, per patient-year of follow-up, were combined in a random-effects Bayesian NMA. The pairwise comparison between each regimen and for each outcome was estimated. The NMA was dominated by 15 large-scale trials with between 1984 and 18\u2009898 patient-years of follow-up. Combinations of drug groups showed incremental benefits on outcomes over single groups. The most effective combinations were ARNI+BB\u2009+\u2009MRA and ACEI+BB\u2009+\u2009MRA\u2009+\u2009IVA, showing reductions in all-cause mortality (vs. placebo) of 62% and 59%, respectively; hazard ratios were 0.38 [credible interval (CrI) 0.20\u20130.65] and 0.41 (CrI 0.21\u20130.70); and in all-cause hospitalizations with reductions of 42% for both. These two combinations were also the most effective for the other outcomes studied.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our analysis shows that the incremental use of combinations of disease-modifying therapies has resulted in the progressive improvement in mortality and hospitalization outcomes in HFrEF. Our findings support the current guideline recommendations.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ejhf.1234","type":"journal-article","created":{"date-parts":[[2018,5,28]],"date-time":"2018-05-28T01:34:52Z","timestamp":1527471292000},"page":"1315-1322","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":122,"title":["Incremental Benefit of Drug Therapies for Chronic Heart Failure with Reduced Ejection Fraction: A Network Meta-Analysis"],"prefix":"10.1093","volume":"20","author":[{"given":"Michel","family":"Komajda","sequence":"first","affiliation":[{"name":"Department of Cardiology, Saint Joseph Hospital , Paris ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"B\u00f6hm","sequence":"additional","affiliation":[{"name":"Universit\u00e4tsklinikum des Saarlandes, Universit\u00e4t des Saarlandes, Klinik f\u00fcr Innere Medizin III , Homburg\/Saar ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey S.","family":"Borer","sequence":"additional","affiliation":[{"name":"Howard Gilman and Schiavone Institutes, State University of New York Downstate Medical Center , Brooklyn and New York, NY ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian","family":"Ford","sequence":"additional","affiliation":[{"name":"Robertson Centre for Biostatistics, University of Glasgow , Glasgow ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luigi","family":"Tavazzi","sequence":"additional","affiliation":[{"name":"Maria Cecilia Hospital-GVM Care and Research, Ettore Sansavini Health Science Foundation , Cotignola ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthieu","family":"Pannaux","sequence":"additional","affiliation":[{"name":"Institut de Recherches Internationales Servier , Suresnes ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karl","family":"Swedberg","sequence":"additional","affiliation":[{"name":"Department of Molecular and Clinical Medicine, Sahlgrenska Academy, University of Gothenburg, G\u00f6teborg, Sweden, and National Heart and Lung Institute, Imperial College , London ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2018,6,19]]},"reference":[{"key":"2026011721251745000_ejhf1234-bib-0001","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1002\/ejhf.592","article-title":"Developed with the special contribution of the Heart Failure Association (HFA) of the ESC","volume":"18","author":"Ponikowski","year":"2016","journal-title":"Eur J Heart Fail"},{"key":"2026011721251745000_ejhf1234-bib-0002","doi-asserted-by":"crossref","first-page":"1224","DOI":"10.1161\/CIRCULATIONAHA.117.027472","article-title":"Trends in heart failure incidence in 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