{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T02:46:45Z","timestamp":1785293205406,"version":"3.55.0"},"reference-count":40,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2022,4,12]],"date-time":"2022-04-12T00:00:00Z","timestamp":1649721600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Intern Med"],"published-print":{"date-parts":[[2022,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Following the availability of new drugs for chronic heart failure (HF) with reduced ejection fraction (HFrEF), we sought to provide an updated and comparative synthesis of the evidence on HFrEF pharmacotherapy efficacy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We performed a Bayesian network meta\u2010analysis of phase 2 and 3 randomized controlled trials (RCTs) of medical therapy in HFrEF patient cohorts with more than 90% of the participants with left ventricular ejection fraction less than 45% and all\u2010cause mortality reported.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Sixty\u2010nine RCTs, accounting for 91,741 subjects, were evaluated. The step\u2010wise introduction of new drugs progressively decreased the risk of all\u2010cause death, up to reaching a random\u2010effects hazard ratio (HR) of 0.43 (95% credible intervals [CrI] 0.27\u20130.63) with beta blockers (BB), angiotensin\u2010converting enzyme inhibitors (ACEi), and mineralocorticoid receptor antagonist (MRA) versus placebo. The risk was further reduced by adding sodium\u2013glucose cotransporter\u20102 inhibitors (SGLT2i; HR 0.38, 95% CrI 0.22\u20130.60), ivabradine (HR 0.39, 95% CrI 0.21\u20130.64), or vericiguat (HR 0.40, 95% CrI 0.22\u20130.65) to neurohormonal inhibitors, and by angiotensin receptor\u2013neprilysin inhibitor (ARNI), BB, and MRA (HR 0.36, 95% CrI 0.20\u20130.60). In a sensitivity analysis considering the ARNI and non\u2010ARNI subgroups of SGLT2i RCTs, the combination SGLT2i\u00a0+\u00a0ARNI\u00a0+\u00a0BB\u00a0+\u00a0MRA was associated with the lowest HR (0.28, 95% CrI 0.16\u20130.45 vs. 0.40, 95% CrI 0.24\u20130.60 for SGLT2i\u00a0+\u00a0BB\u00a0+\u00a0ACEi\u00a0+\u00a0MRA). Consistent results were obtained in sensitivity analyses and by calculating surface under the cumulative ranking area, as well as for cardiovascular mortality (information available for 56 RCTs), HF hospitalization (45 RCTs), and all\u2010cause hospitalization (26 RCTs).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Combination medical therapy including neurohormonal inhibitors and newer drugs, especially ARNI and SGLT2i, confers the maximum benefit with regard to HFrEF prognosis.<\/jats:p><\/jats:sec>","DOI":"10.1111\/joim.13487","type":"journal-article","created":{"date-parts":[[2022,3,25]],"date-time":"2022-03-25T08:55:01Z","timestamp":1648198501000},"page":"333-349","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Network meta\u2010analysis of medical therapy efficacy in more than 90,000 patients with heart failure and reduced ejection fraction"],"prefix":"10.1111","volume":"292","author":[{"given":"Vincenzo","family":"De Marzo","sequence":"first","affiliation":[{"name":"Department of Internal Medicine University of Genova  Genova Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7732-0887","authenticated-orcid":false,"given":"Gianluigi","family":"Savarese","sequence":"additional","affiliation":[{"name":"Division of Cardiology Department of Medicine Karolinska Institutet  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucia","family":"Tricarico","sequence":"additional","affiliation":[{"name":"Cardiology Unit Ospedali Riuniti di Foggia  Foggia Italy"},{"name":"Department of Medical and Surgical Sciences University of Foggia  Foggia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sofia","family":"Hassan","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine University of Genova  Genova Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Massimo","family":"Iacoviello","sequence":"additional","affiliation":[{"name":"Cardiology Unit Ospedali Riuniti di Foggia  Foggia Italy"},{"name":"Department of Medical and Surgical Sciences University of Foggia  Foggia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Italo","family":"Porto","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine University of Genova  Genova Italy"},{"name":"Cardiology Unit Cardio\u2010Thoracic and Vascular Department IRCCS Ospedale Policlinico San Martino  Genova Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7167-7287","authenticated-orcid":false,"given":"Pietro","family":"Ameri","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine University of Genova  Genova Italy"},{"name":"Cardiology Unit Cardio\u2010Thoracic and Vascular Department IRCCS Ospedale Policlinico San Martino  Genova Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,4,12]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehab368"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehw128"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCHEARTFAILURE.116.003529"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/ejhf.1234"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1911303"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2022190"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1915928"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1177\/0272989X12458724"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.7326\/M14-2385"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/ehjcvp\/pvab088"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.l4898"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0099682"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jclinepi.2010.09.011"},{"key":"e_1_2_8_15_1","unstructured":"PlummerM.JAGS: a program for analysis of Bayesian graphical models using Gibbs sampling.3rd International Workshop on Distributed Statistical Computing (DSC 2003); 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