{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:04:31Z","timestamp":1792785871169,"version":"4.5.0"},"reference-count":30,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T00:00:00Z","timestamp":1789516800000},"content-version":"am","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Merck Sharp & Dohme LLC"},{"name":"Merck & Co., Inc., Rahway, NJ, USA","id":[{"id":"https:\/\/ror.org\/02891sr49","id-type":"ROR","asserted-by":"crossref"}]},{"DOI":"10.13039\/100004326","name":"Bayer AG","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004326","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The VICTOR trial did not meet its primary composite endpoint of cardiovascular death or first hospitalization for heart failure (HF) but demonstrated a nominally significant reduction in the prespecified and powered endpoint of cardiovascular death with vericiguat in patients with HF and reduced ejection fraction (HFrEF). Bayesian and actuarial methods offer complementary frameworks to quantify the probability and lifetime implications of this mortality benefit.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This post hoc analysis of the VICTOR trial applied Bayesian and actuarial analyses. Bayesian analysis estimated the probability that vericiguat reduces mortality, integrating trial data with prior evidence. Actuarial analysis used restricted mean survival time (RMST) to quantify event-free survival at 1 and 2 years, and age-based Cox proportional hazards modelling to project lifetime survival gains across ages 45\u201380.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Bayesian analyses showed a consistently high probability of mortality benefit with vericiguat, regardless of whether sceptical or optimistic prior evidence was weighted. For cardiovascular mortality, the sceptical prior yielded a 98.4% posterior probability of any benefit, a 77.6% probability of at least a 10% relative reduction, and a 20.4% probability of at least a 20% reduction. The VICTORIA-based optimistic prior yielded 99.1%, 60.7%, and 2.2%, respectively. Similar results were observed for all-cause mortality. Actuarial analyses demonstrated greater event-free survival with vericiguat over 1 and 2 years. Lifetime projections suggested that vericiguat may extend overall survival across a broad age range, with the largest gains observed of \u223c1.6 to 1.9 years for those aged 55 to 60 at randomization.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>In this post hoc analysis, Bayesian and actuarial methods provided hypothesis-generating evidence of a cardiovascular mortality benefit with vericiguat in HFrEF, an endpoint for which the trial was prospectively powered, that warrants prospective confirmation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/ejhf\/xuag267","type":"journal-article","created":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T11:53:05Z","timestamp":1789127585000},"source":"Crossref","is-referenced-by-count":0,"title":["Mortality benefit and lifetime survival gains with vericiguat in HFrEF: Bayesian and actuarial analyses of the VICTOR trial"],"prefix":"10.1093","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7174-8604","authenticated-orcid":false,"given":"Francesco","family":"Fioretti","sequence":"first","affiliation":[{"name":"Baylor Scott and White Research Institute , 3434 Live Oak St Ste 501, Dallas, TX 75204 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7456-1570","authenticated-orcid":false,"given":"Faiez","family":"Zannad","sequence":"additional","affiliation":[{"name":"Division of Hypertension and Heart Failure, Universit\u00e9 de Lorraine, Inserm CIC 1433, CHRU , Nancy ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Derek","family":"Cyr","sequence":"additional","affiliation":[{"name":"Duke Clinical Research Institute, Duke University School of Medicine , Durham, NC ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin J","family":"Anstrom","sequence":"additional","affiliation":[{"name":"Gillings School of Global Public Health, University of North Carolina , Chapel Hill, NC ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irina","family":"Barash","sequence":"additional","affiliation":[{"name":"Merck & Co., Inc. , Rahway, NJ ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc P","family":"Bonaca","sequence":"additional","affiliation":[{"name":"Department of Medicine-Cardiology, University of Colorado School of Medicine , Aurora, CO ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Corda","sequence":"additional","affiliation":[{"name":"Bayer AG , Basel ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1681-9187","authenticated-orcid":false,"given":"Anique","family":"Ducharme","sequence":"additional","affiliation":[{"name":"Department of Medicine, Montr\u00e9al Heart Institute, Universit\u00e9 de Montr\u00e9al , Quebec, Montr\u00e9al ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justin","family":"Ezekowitz","sequence":"additional","affiliation":[{"name":"Canadian VIGOUR Centre, University of Alberta , Edmonton, AB ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anuradha","family":"Lala","sequence":"additional","affiliation":[{"name":"Department of Population Health Science and Policy, Mount Sinai Fuster Heart Hospital, Icahn School of Medicine at Mount Sinai , New York, NY ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolyn S P","family":"Lam","sequence":"additional","affiliation":[{"name":"Department of Cardiology, National Heart Centre Singapore and Duke-National University of Singapore Medical School , Singapore ,","place":["Singapore"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eldrin F","family":"Lewis","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine, Stanford University School of Medicine , Stanford, CA ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"JoAnn","family":"Lindenfeld","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine, Vanderbilt University Medical Center , Nashville, TN ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7269-6391","authenticated-orcid":false,"given":"Ciaran J","family":"McMullan","sequence":"additional","affiliation":[{"name":"Merck & Co., Inc. , Rahway, NJ ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert J","family":"Mentz","sequence":"additional","affiliation":[{"name":"Duke Clinical Research Institute, Duke University School of Medicine , Durham, NC ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Metra","sequence":"additional","affiliation":[{"name":"Cardiology, IRCCS San Raffaele Scientific Institute and Vita-Salute San Raffaele University , Milan ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alanna A","family":"Morris","sequence":"additional","affiliation":[{"name":"Emory University School of Medicine, Emory Cardiovascular Clinical Research Institute , Atlanta, GA ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher M","family":"O\u2019Connor","sequence":"additional","affiliation":[{"name":"Inova Schar Heart and Vascular , Falls Church, VA ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piotr","family":"Ponikowski","sequence":"additional","affiliation":[{"name":"Institute of Heart Diseases, Wroclaw Medical University , Wroclaw ,","place":["Poland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yogesh N V","family":"Reddy","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Diseases, Mayo Clinic , Rochester, MN ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4023-2263","authenticated-orcid":false,"given":"Giuseppe","family":"Rosano","sequence":"additional","affiliation":[{"name":"Department of Cardiology, San Raffaele Open University of Rome , Rome ,","place":["Italy"]},{"name":"Centre for Clinical and Basic Research, IRCCS San Raffaele , Rome ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clara","family":"Saldarriaga","sequence":"additional","affiliation":[{"name":"CardioVID Clinic, University of Antioquia , Medell\u00edn ,","place":["Colombia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5502-7882","authenticated-orcid":false,"given":"Michele","family":"Senni","sequence":"additional","affiliation":[{"name":"Cardiovascular Department, Division of Cardiology, Papa Giovanni XXIII Hospital , Bergamo ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Udelson","sequence":"additional","affiliation":[{"name":"Tufts Medical Center, Tufts University School of Medicine , Boston, MA ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5417-4415","authenticated-orcid":false,"given":"Adriaan A","family":"Voors","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University of Groningen, University Medical Center Groningen , Groningen ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7683-4720","authenticated-orcid":false,"given":"Javed","family":"Butler","sequence":"additional","affiliation":[{"name":"Baylor Scott and White Research Institute , 3434 Live Oak St Ste 501, Dallas, TX 75204 ,","place":["USA"]},{"name":"Department of Medicine, University of Mississippi , Jackson, 2500 North State Street, Jackson, MS 39216 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,9,16]]},"reference":[{"key":"2026091613063774700_xuag267-B1","doi-asserted-by":"publisher","first-page":"529","DOI":"10.1016\/S0140-6736(25)01851-3","article-title":"Heart failure with reduced ejection fraction","volume":"407","author":"Cannata","year":"2026","journal-title":"Lancet"},{"key":"2026091613063774700_xuag267-B2","doi-asserted-by":"publisher","first-page":"1341","DOI":"10.1016\/S0140-6736(25)01665-4","article-title":"Vericiguat in patients with chronic heart failure and reduced ejection fraction (VICTOR): a double-blind, placebo-controlled, randomised, phase 3 trial","volume":"406","author":"Butler","year":"2025","journal-title":"Lancet"},{"key":"2026091613063774700_xuag267-B3","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1002\/sim.3748","article-title":"Hierarchical testing of multiple endpoints in group-sequential trials","volume":"29","author":"Glimm","year":"2010","journal-title":"Stat Med"},{"key":"2026091613063774700_xuag267-B4","doi-asserted-by":"publisher","first-page":"1067","DOI":"10.1016\/S0140-6736(24)01295-9","article-title":"Bayesian statistics for clinical research","volume":"404","author":"Goligher","year":"2024","journal-title":"Lancet"},{"key":"2026091613063774700_xuag267-B5","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1016\/j.cjca.2024.11.002","article-title":"Bayesian analytical methods in cardiovascular clinical trials: why, when, and how","volume":"41","author":"Heuts","year":"2025","journal-title":"Can J Cardiol"},{"key":"2026091613063774700_xuag267-B6","doi-asserted-by":"publisher","first-page":"984","DOI":"10.1016\/j.jchf.2020.08.004","article-title":"Estimating the lifetime benefits of treatments for heart failure","volume":"8","author":"Ferreira","year":"2020","journal-title":"JACC Heart Fail"},{"key":"2026091613063774700_xuag267-B7","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyaf191","article-title":"Diverging conclusions from risk difference and difference in restricted mean survival time in quantifying absolute treatment effect heterogeneity","volume":"54","author":"Maas","year":"2025","journal-title":"Int J Epidemiol"},{"key":"2026091613063774700_xuag267-B8","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1002\/ejhf.3501","article-title":"Vericiguat global study in participants with chronic heart failure: design of the VICTOR trial","volume":"27","author":"Reddy","year":"2025","journal-title":"Eur J Heart Fail"},{"key":"2026091613063774700_xuag267-B9","doi-asserted-by":"publisher","first-page":"1426","DOI":"10.1002\/ejhf.3598","article-title":"Baseline characteristics of contemporary trial participants with heart failure and reduced ejection fraction: the VICTOR trial","volume":"27","author":"Saldarriaga","year":"2025","journal-title":"Eur J Heart Fail"},{"key":"2026091613063774700_xuag267-B10","doi-asserted-by":"publisher","first-page":"543","DOI":"10.1164\/rccm.202006-2381CP","article-title":"Using Bayesian methods to augment the interpretation of critical care trials. An overview of theory and example reanalysis of the alveolar recruitment for acute respiratory distress syndrome trial","volume":"203","author":"Zampieri","year":"2021","journal-title":"Am J Respir Crit Care Med"},{"key":"2026091613063774700_xuag267-B11","doi-asserted-by":"publisher","first-page":"1883","DOI":"10.1056\/NEJMoa1915928","article-title":"Vericiguat in patients with heart failure and reduced ejection fraction","volume":"382","author":"Armstrong","year":"2020","journal-title":"N Engl J Med"},{"key":"2026091613063774700_xuag267-B12","doi-asserted-by":"publisher","first-page":"683","DOI":"10.1093\/eurheartj\/ehaf655","article-title":"Vericiguat and mortality in heart failure and reduced ejection fraction: the VICTOR trial","volume":"47","author":"Butler","year":"2026","journal-title":"Eur Heart J"},{"key":"2026091613063774700_xuag267-B13","doi-asserted-by":"publisher","first-page":"1351","DOI":"10.1016\/S0140-6736(25)01682-4","article-title":"Vericiguat for patients with heart failure and reduced ejection fraction across the risk spectrum: an individual participant data analysis of the VICTORIA and VICTOR trials","volume":"406","author":"Zannad","year":"2025","journal-title":"Lancet"},{"key":"2026091613063774700_xuag267-B14","doi-asserted-by":"publisher","first-page":"158","DOI":"10.1016\/j.jclinepi.2020.12.021","article-title":"Bayes\u2019 rule in diagnosis","volume":"131","author":"Bours","year":"2021","journal-title":"J Clin Epidemiol"},{"key":"2026091613063774700_xuag267-B15","doi-asserted-by":"publisher","first-page":"1500","DOI":"10.1016\/S0140-6736(05)66422-7","article-title":"Refining clinical diagnosis with likelihood ratios","volume":"365","author":"Grimes","year":"2005","journal-title":"Lancet"},{"key":"2026091613063774700_xuag267-B16","doi-asserted-by":"publisher","first-page":"210","DOI":"10.1186\/s12911-024-02610-3","article-title":"From pre-test and post-test probabilities to medical decision making","volume":"24","author":"Nixon","year":"2024","journal-title":"BMC Med Inform Decis Mak"},{"key":"2026091613063774700_xuag267-B17","doi-asserted-by":"publisher","first-page":"1087","DOI":"10.1161\/CIRCULATIONAHA.122.063602","article-title":"Cost-effectiveness of vericiguat in patients with heart failure with reduced ejection fraction: the VICTORIA randomized clinical trial","volume":"148","author":"Chew","year":"2023","journal-title":"Circulation"},{"key":"2026091613063774700_xuag267-B18","doi-asserted-by":"publisher","first-page":"3052","DOI":"10.1093\/eurheartj\/ehag110","article-title":"Heart failure in the elderly: epidemiology, mechanisms, and management","volume":"47","author":"de Boer","year":"2026","journal-title":"Eur Heart J"},{"key":"2026091613063774700_xuag267-B19","doi-asserted-by":"publisher","first-page":"2513","DOI":"10.1016\/j.jacc.2025.08.054","article-title":"Pharmacologic treatment of heart failure with reduced ejection fraction: an updated systematic review and network meta-analysis","volume":"86","author":"van Essen","year":"2025","journal-title":"J Am Coll Cardiol"},{"key":"2026091613063774700_xuag267-B20","doi-asserted-by":"publisher","first-page":"1246","DOI":"10.1016\/j.jchf.2023.06.020","article-title":"Age, sex, and outcomes in heart failure with reduced EF: insights from the VICTORIA trial","volume":"11","author":"Lam","year":"2023","journal-title":"JACC Heart Fail"},{"key":"2026091613063774700_xuag267-B21","doi-asserted-by":"publisher","first-page":"587","DOI":"10.1001\/archinternmed.2010.18","article-title":"Cautionary tales in the interpretation of clinical studies involving older persons","volume":"170","author":"Scott","year":"2010","journal-title":"Arch Intern Med"},{"key":"2026091613063774700_xuag267-B22","doi-asserted-by":"publisher","first-page":"577","DOI":"10.7326\/0003-4819-124-6-199603150-00007","article-title":"Estimating treatment benefits for the elderly: the effect of competing risks","volume":"124","author":"Welch","year":"1996","journal-title":"Ann Intern Med"},{"key":"2026091613063774700_xuag267-B23","doi-asserted-by":"publisher","first-page":"2492","DOI":"10.1016\/j.jacc.2025.09.021","article-title":"Outpatient worsening in HFrEF: a signal, not a standard","volume":"86","author":"St\u00f6rk","year":"2025","journal-title":"J Am Coll Cardiol"},{"key":"2026091613063774700_xuag267-B24","doi-asserted-by":"publisher","first-page":"3791","DOI":"10.1002\/ehf2.14050","article-title":"Vericiguat and NT-proBNP in patients with heart failure with reduced ejection fraction: analyses from the VICTORIA trial","volume":"9","author":"Senni","year":"2022","journal-title":"ESC Heart Fail"},{"key":"2026091613063774700_xuag267-B25","doi-asserted-by":"publisher","first-page":"2471","DOI":"10.1016\/j.jacc.2025.08.051","article-title":"Effect of vericiguat on total heart failure events in compensated outpatients with HFrEF: insights from VICTOR","volume":"86","author":"Zannad","year":"2025","journal-title":"J Am Coll Cardiol"},{"key":"2026091613063774700_xuag267-B26","doi-asserted-by":"publisher","first-page":"949","DOI":"10.1007\/s10741-024-10412-y","article-title":"Beyond quadruple therapy: the potential roles for ivabradine, vericiguat, and omecamtiv mecarbil in the therapeutic armamentarium","volume":"29","author":"Shoji","year":"2024","journal-title":"Heart Fail Rev"},{"key":"2026091613063774700_xuag267-B27","doi-asserted-by":"publisher","first-page":"369","DOI":"10.1177\/0272989X12475091","article-title":"The \u201chazards\u201d of extrapolating survival curves","volume":"33","author":"Davies","year":"2013","journal-title":"Med Decis Making"},{"key":"2026091613063774700_xuag267-B28","doi-asserted-by":"publisher","first-page":"2455","DOI":"10.1177\/0962280216688034","article-title":"Flexible modeling of the hazard rate and treatment effects in long-term survival studies","volume":"26","author":"Hagar","year":"2017","journal-title":"Stat Methods Med Res"},{"key":"2026091613063774700_xuag267-B29","doi-asserted-by":"publisher","first-page":"2763","DOI":"10.1002\/(SICI)1097-0258(19961230)15:24&lt;2763::AID-SIM319&gt;3.0.CO;2-O","article-title":"Evaluation of long-term survival: use of diagnostics and robust estimators with Cox's proportional hazards model","volume":"15","author":"Valsecchi","year":"1996","journal-title":"Stat Med"},{"key":"2026091613063774700_xuag267-B30","doi-asserted-by":"publisher","first-page":"347","DOI":"10.1016\/j.jval.2023.12.008","article-title":"Perils of randomized controlled trial survival extrapolation assuming treatment effect waning: why the distinction between marginal and conditional estimates matters","volume":"27","author":"Jennings","year":"2024","journal-title":"Value Health"}],"container-title":["European Journal of Heart Failure"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/eurjhf\/advance-article-pdf\/doi\/10.1093\/ejhf\/xuag267\/71127335\/xuag267.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/eurjhf\/advance-article-pdf\/doi\/10.1093\/ejhf\/xuag267\/71127335\/xuag267.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T17:06:42Z","timestamp":1789578402000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/eurjhf\/advance-article\/doi\/10.1093\/ejhf\/xuag267\/8802458"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,16]]},"references-count":30,"URL":"https:\/\/doi.org\/10.1093\/ejhf\/xuag267","relation":{},"ISSN":["1388-9842","1879-0844"],"issn-type":[{"value":"1388-9842","type":"print"},{"value":"1879-0844","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,16]]},"article-number":"xuag267"}}