{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T16:12:49Z","timestamp":1793895169045,"version":"4.8.0"},"reference-count":87,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circ: Heart Failure"],"published-print":{"date-parts":[[2017,1]]},"abstract":"<jats:sec>\n                    <jats:title>Background\u2014<\/jats:title>\n                    <jats:p>Treatments that reduce mortality and morbidity in patients with heart failure with reduced ejection fraction, including angiotensin-converting enzyme inhibitors (ACEI), angiotensin receptor blockers (ARB), \u03b2-blockers (BB), mineralocorticoid receptor antagonists (MRA), and angiotensin receptor\u2013neprilysin inhibitors (ARNI), have not been studied in a head-to-head fashion. This network meta-analysis aimed to compare the efficacy of these drugs and their combinations regarding all-cause mortality in patients with heart failure with reduced ejection fraction.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and Results\u2014<\/jats:title>\n                    <jats:p>A systematic literature review identified 57 randomized controlled trials published between 1987 and 2015, which were compared in terms of study and patient characteristics, baseline risk, outcome definitions, and the observed treatment effects. Despite differences identified in terms of study duration, New York Heart Association class, ejection fraction, and use of background digoxin, a network meta-analysis was considered feasible and all trials were analyzed simultaneously. The random-effects network meta-analysis suggested that the combination of ACEI+BB+MRA was associated with a 56% reduction in mortality versus placebo (hazard ratio 0.44, 95% credible interval 0.26\u20130.66); ARNI+BB+MRA was associated with the greatest reduction in all-cause mortality versus placebo (hazard ratio 0.37, 95% credible interval 0.19\u20130.65). A sensitivity analysis that did not account for background therapy suggested that ARNI monotherapy is more efficacious than ACEI or ARB monotherapy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions\u2014<\/jats:title>\n                    <jats:p>The network meta-analysis showed that treatment with ACEI, ARB, BB, MRA, and ARNI and their combinations were better than the treatment with placebo in reducing all-cause mortality, with the exception of ARB monotherapy and ARB plus ACEI. The combination of ARNI+BB+MRA resulted in the greatest mortality reduction.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/circheartfailure.116.003529","type":"journal-article","created":{"date-parts":[[2017,1,13]],"date-time":"2017-01-13T22:10:19Z","timestamp":1484345419000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":209,"title":["Thirty Years of Evidence on the Efficacy of Drug Treatments for Chronic Heart Failure With Reduced Ejection Fraction"],"prefix":"10.1161","volume":"10","author":[{"given":"Heather","family":"Burnett","sequence":"first","affiliation":[{"name":"From the Mapi, Health Economics and Outcomes Research, Dundas, Canada (H.B.); Mapi, Health Economics and Outcomes Research, Boston, MA (A.E.); Department of Cardiology, University of Groningen, The Netherlands (A.A.V.); Cardiovascular Department, Hospital Papa Giovanni XXIII, Bergamo, Italy (M.S.); British Heart Foundation Cardiovascular Research Centre, University of Glasgow, UK (J.J.V.M.); Global Patient Access, Novartis Pharma AG, Postfach, CH-4002 Basel, Switzerland (C.D.); and Mapi, Health..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy","family":"Earley","sequence":"additional","affiliation":[{"name":"From the Mapi, Health Economics and Outcomes Research, Dundas, Canada (H.B.); Mapi, Health Economics and Outcomes Research, Boston, MA (A.E.); Department of Cardiology, University of Groningen, The Netherlands (A.A.V.); Cardiovascular Department, Hospital Papa Giovanni XXIII, Bergamo, Italy (M.S.); British Heart Foundation Cardiovascular Research Centre, University of Glasgow, UK (J.J.V.M.); Global Patient Access, Novartis Pharma AG, Postfach, CH-4002 Basel, Switzerland (C.D.); and Mapi, Health..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriaan A.","family":"Voors","sequence":"additional","affiliation":[{"name":"From the Mapi, Health Economics and Outcomes Research, Dundas, Canada (H.B.); Mapi, Health Economics and Outcomes Research, Boston, MA (A.E.); Department of Cardiology, University of Groningen, The Netherlands (A.A.V.); Cardiovascular Department, Hospital Papa Giovanni XXIII, Bergamo, Italy (M.S.); British Heart Foundation Cardiovascular Research Centre, University of Glasgow, UK (J.J.V.M.); Global Patient Access, Novartis Pharma AG, Postfach, CH-4002 Basel, Switzerland (C.D.); and Mapi, Health..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michele","family":"Senni","sequence":"additional","affiliation":[{"name":"From the Mapi, Health Economics and Outcomes Research, Dundas, Canada (H.B.); Mapi, Health Economics and Outcomes Research, Boston, MA (A.E.); Department of Cardiology, University of Groningen, The Netherlands (A.A.V.); Cardiovascular Department, Hospital Papa Giovanni XXIII, Bergamo, Italy (M.S.); British Heart Foundation Cardiovascular Research Centre, University of Glasgow, UK (J.J.V.M.); Global Patient Access, Novartis Pharma AG, Postfach, CH-4002 Basel, Switzerland (C.D.); and Mapi, Health..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John J.V.","family":"McMurray","sequence":"additional","affiliation":[{"name":"From the Mapi, Health Economics and Outcomes Research, Dundas, Canada (H.B.); Mapi, Health Economics and Outcomes Research, Boston, MA (A.E.); Department of Cardiology, University of Groningen, The Netherlands (A.A.V.); Cardiovascular Department, Hospital Papa Giovanni XXIII, Bergamo, Italy (M.S.); British Heart Foundation Cardiovascular Research Centre, University of Glasgow, UK (J.J.V.M.); Global Patient Access, Novartis Pharma AG, Postfach, CH-4002 Basel, Switzerland (C.D.); and Mapi, Health..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Celine","family":"Deschaseaux","sequence":"additional","affiliation":[{"name":"From the Mapi, Health Economics and Outcomes Research, Dundas, Canada (H.B.); Mapi, Health Economics and Outcomes Research, Boston, MA (A.E.); Department of Cardiology, University of Groningen, The Netherlands (A.A.V.); Cardiovascular Department, Hospital Papa Giovanni XXIII, Bergamo, Italy (M.S.); British Heart Foundation Cardiovascular Research Centre, University of Glasgow, UK (J.J.V.M.); Global Patient Access, Novartis Pharma AG, Postfach, CH-4002 Basel, Switzerland (C.D.); and Mapi, Health..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shannon","family":"Cope","sequence":"additional","affiliation":[{"name":"From the Mapi, Health Economics and Outcomes Research, Dundas, Canada (H.B.); Mapi, Health Economics and Outcomes Research, Boston, MA (A.E.); Department of Cardiology, University of Groningen, The Netherlands (A.A.V.); Cardiovascular Department, Hospital Papa Giovanni XXIII, Bergamo, Italy (M.S.); British Heart Foundation Cardiovascular Research Centre, University of Glasgow, UK (J.J.V.M.); Global Patient Access, Novartis Pharma AG, Postfach, CH-4002 Basel, Switzerland (C.D.); and Mapi, Health..."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurjhf\/hfs105"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.109.192666"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjcard.2007.11.061"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1093\/europace\/eup304"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehw128"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIR.0000000000000435"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1409077"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1186\/1741-7015-11-159"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1002\/sim.3594"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1177\/0272989X12458724"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jval.2011.04.002"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jclinepi.2009.06.005"},{"key":"e_1_3_4_14_2","volume-title":"CRD\u2019s Guidance for Undertaking Reviews in Health Care","year":"2008","unstructured":"CRD\u2019s Guidance for Undertaking Reviews in Health Care. Layerthorpe, York, UK: Centre for Reviews and Dissemination, University of York; 2008."},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1186\/1741-7015-12-93"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.331.7521.897"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1524-4733.2008.00347.x"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1002\/sim.1875"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1177\/135581969900400112"},{"key":"e_1_3_4_20_2","volume-title":"Bayesian Approaches to Clinical Trials and Health-Care Evaluation","author":"Spiegelhalter DJ","year":"2004","unstructured":"Spiegelhalter DJ, Abrams KR, Myles JP.Bayesian Approaches to Clinical Trials and Health-Care Evaluation. West Sussex, England: John Wiley & Sons; 2004."},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1002\/sim.3680"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00192366"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198706043162301"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.eurheartj.a060844"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9149(93)90657-X"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199209033271003"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199108013250501"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1002\/j.1552-4604.1995.tb04107.x"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9149(99)80624-9"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1097\/00005344-198700003-00021"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9149(92)90618-9"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.1988.03720040031022"},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9149(89)90411-6"},{"key":"e_1_3_4_34_2","first-page":"27","article-title":"Effects of fosinopril on exercise tolerance, symptoms, and clinical outcomes in patients with decompensated heart failure.","volume":"5","author":"Shettigar U","year":"1999","unstructured":"Shettigar U, Hare T, Gelperin K, Ilgenfritz JP, Deitchman D, Blumenthal M. Effects of fosinopril on exercise tolerance, symptoms, and clinical outcomes in patients with decompensated heart failure. Congest Heart Fail. 1999;5:27\u201334.","journal-title":"Congest Heart Fail"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0735-1097(98)00464-1"},{"key":"e_1_3_4_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-8703(00)90037-1"},{"key":"e_1_3_4_37_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.100.22.2224"},{"key":"e_1_3_4_38_2","doi-asserted-by":"publisher","DOI":"10.1067\/mhj.2003.161"},{"key":"e_1_3_4_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(97)01187-2"},{"key":"e_1_3_4_40_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(00)02213-3"},{"key":"e_1_3_4_41_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0167-5273(00)00426-5"},{"key":"e_1_3_4_42_2","doi-asserted-by":"publisher","DOI":"10.1016\/0735-1097(95)80020-H"},{"key":"e_1_3_4_43_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0735-1097(97)00253-2"},{"key":"e_1_3_4_44_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(03)14284-5"},{"key":"e_1_3_4_45_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0167-5273(02)00154-7"},{"key":"e_1_3_4_46_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199909023411001"},{"key":"e_1_3_4_47_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10557-008-6116-9"},{"key":"e_1_3_4_48_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejheart.2003.12.019"},{"key":"e_1_3_4_49_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa010713"},{"key":"e_1_3_4_50_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.99.8.990"},{"key":"e_1_3_4_51_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200105313442202"},{"key":"e_1_3_4_52_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.90.4.1765"},{"key":"e_1_3_4_53_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(98)11181-9"},{"key":"e_1_3_4_54_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9149(00)00796-7"},{"key":"e_1_3_4_55_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.289.6.712"},{"key":"e_1_3_4_56_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejheart.2004.10.015"},{"key":"e_1_3_4_57_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(99)04440-2"},{"key":"e_1_3_4_58_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-8703(99)70083-9"},{"key":"e_1_3_4_59_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1388-9842(00)00078-7"},{"key":"e_1_3_4_60_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.94.11.2807"},{"key":"e_1_3_4_61_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.94.11.2793"},{"key":"e_1_3_4_62_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejheart.2003.12.007"},{"key":"e_1_3_4_63_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1071-9164(97)90013-0"},{"key":"e_1_3_4_64_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.94.11.2800"},{"key":"e_1_3_4_65_2","doi-asserted-by":"publisher","DOI":"10.1067\/mhj.2002.121807"},{"key":"e_1_3_4_66_2","doi-asserted-by":"publisher","DOI":"10.1067\/mhj.2002.121269"},{"key":"e_1_3_4_67_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.92.6.1499"},{"key":"e_1_3_4_68_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199605233342101"},{"key":"e_1_3_4_69_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.fjc.0000159880.12067.34"},{"key":"e_1_3_4_70_2","first-page":"321","article-title":"Effects of carvedilol on left ventricular diastolic function and chamber volumes in advanced heart failure.","volume":"53","author":"Palazzuoli A","year":"2005","unstructured":"Palazzuoli A, Quatrini I, Vecchiato L, Scali C, De Paola V, Iovine F, Martini G, Nuti R. Effects of carvedilol on left ventricular diastolic function and chamber volumes in advanced heart failure. Minerva Cardioangiol. 2005;53:321\u2013328.","journal-title":"Minerva Cardioangiol"},{"key":"e_1_3_4_71_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1388-9842(00)00120-3"},{"key":"e_1_3_4_72_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0195-668X(03)00477-9"},{"key":"e_1_3_4_73_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.101.4.378"},{"key":"e_1_3_4_74_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(03)14283-3"},{"key":"e_1_3_4_75_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurjhf\/hfn015"},{"key":"e_1_3_4_76_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1009492"},{"key":"e_1_3_4_77_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0735-1097(02)01965-4"},{"key":"e_1_3_4_78_2","doi-asserted-by":"publisher","DOI":"10.1097\/MAJ.0b013e31829dd6b1"},{"key":"e_1_3_4_79_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jval.2014.08.595"},{"key":"e_1_3_4_80_2","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-134-7-200104030-00008"},{"key":"e_1_3_4_81_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.f55"},{"key":"e_1_3_4_82_2","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.12012"},{"key":"e_1_3_4_83_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0735-1097(01)01775-2"},{"key":"e_1_3_4_84_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0009946"},{"key":"e_1_3_4_85_2","doi-asserted-by":"publisher","DOI":"10.1002\/ejhf.603"},{"key":"e_1_3_4_86_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijcard.2015.12.010"},{"key":"e_1_3_4_87_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehu455"},{"key":"e_1_3_4_88_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2288-11-61"}],"container-title":["Circulation: Heart Failure"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/CIRCHEARTFAILURE.116.003529","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,12]],"date-time":"2024-05-12T21:33:48Z","timestamp":1715549628000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/CIRCHEARTFAILURE.116.003529"}},"subtitle":["A Network Meta-Analysis"],"short-title":[],"issued":{"date-parts":[[2017,1]]},"references-count":87,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2017,1]]}},"alternative-id":["10.1161\/CIRCHEARTFAILURE.116.003529"],"URL":"https:\/\/doi.org\/10.1161\/circheartfailure.116.003529","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.727206733.793529068","asserted-by":"object"}]},"ISSN":["1941-3289","1941-3297"],"issn-type":[{"value":"1941-3289","type":"print"},{"value":"1941-3297","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,1]]},"assertion":[{"value":"2016-08-23","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2016-12-15","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2017-01-13","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e003529"}}