{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T11:50:06Z","timestamp":1769082606332,"version":"3.49.0"},"reference-count":13,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2025,12,20]],"date-time":"2025-12-20T00:00:00Z","timestamp":1766188800000},"content-version":"vor","delay-in-days":1739,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2021,3,17]],"date-time":"2021-03-17T00:00:00Z","timestamp":1615939200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2021,6,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>We applied the restricted mean survival time (RMST) to analyse the survival data reported in the PARADIGM-HT trial in which sacubitril + valsartan was studied in comparison with enalapril in patients with heart failure. The estimates of this parameter were compared with the published values of hazard ratio (HR).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Two endpoints were evaluated: a composite of death or hospitalization and cardiovascular death. Our analyses were performed by considering the original follow-up of 41.4 months and on the basis of a lifetime perspective. All statistical calculations were carried out using specific packages developed under the R-platform.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>According to our RMST analysis, the results for the composite endpoint in the comparison of sacubitril + valsartan vs. enalapril showed an improvement from 32.9 to 34.2 months (gain of 1.25 months). This result is based on a time horizon of 41.4 months. The results for the cardiovascular mortality endpoint showed a RMST of 37.2 months for sacubitril + valsartan vs. 36.2 for enalapril (gain of 0.96 months). In the two lifetime analyses, the improvements were much more relevant and yielded a gain of 25.8 months for the composite endpoint and 27.6 months for survival free from cardiovascular death.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Using the data of the PARADIGM-HT trial, our analysis confirmed that the RMST has documented advantages over the HR, particularly when the clinical study is characterized by a long follow-up. The number needed to treat (NNT) has a more specific methodological role and cannot be replaced by the RMST.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ehf2.13306","type":"journal-article","created":{"date-parts":[[2021,3,17]],"date-time":"2021-03-17T23:41:16Z","timestamp":1616024476000},"page":"2345-2348","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["The Restricted Mean Survival Time as a Replacement for the Hazard Ratio and the Number Needed to Treat in Long-Term Studies"],"prefix":"10.1093","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5829-107X","authenticated-orcid":false,"given":"Andrea","family":"Messori","sequence":"first","affiliation":[{"name":"HTA Unit, Toscana Region Health Service , Florence, Toscana Region ,","place":["Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3283-0987","authenticated-orcid":false,"given":"Laura","family":"Bartoli","sequence":"additional","affiliation":[{"name":"HTA Unit, Toscana Region Health Service , Florence, Toscana Region ,","place":["Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5762-1807","authenticated-orcid":false,"given":"Sabrina","family":"Trippoli","sequence":"additional","affiliation":[{"name":"HTA Unit, Toscana Region Health Service , Florence, Toscana Region ,","place":["Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2021,3,17]]},"reference":[{"key":"2026012114031394600_ehf213306-bib-0001","doi-asserted-by":"crossref","first-page":"127","DOI":"10.7326\/M14-1741","article-title":"Alternatives to hazard ratios for comparing the efficacy or safety of therapies in noninferiority studies","volume":"163","author":"Uno","year":"2015","journal-title":"Ann Intern Med"},{"key":"2026012114031394600_ehf213306-bib-0002","doi-asserted-by":"crossref","first-page":"1692","DOI":"10.1001\/jamaoncol.2017.2797","article-title":"Interpretability of cancer clinical trial results using restricted mean survival time as an alternative to the hazard ratio","volume":"3","author":"Pak","year":"2017","journal-title":"JAMA Oncol"},{"key":"2026012114031394600_ehf213306-bib-0003","doi-asserted-by":"crossref","first-page":"1366","DOI":"10.1161\/CIRCULATIONAHA.119.040680","article-title":"Using the restricted mean survival time difference as an alternative to the hazard ratio for analyzing clinical cardiovascular studies","volume":"140","author":"McCaw","year":"2019","journal-title":"Circulation"},{"key":"2026012114031394600_ehf213306-bib-0004","doi-asserted-by":"crossref","DOI":"10.1161\/CIRCOUTCOMES.119.005918","article-title":"Novel risk modeling approach of atrial fibrillation with restricted mean survival times: application in the Framingham Heart Study community-based cohort","author":"Staerk","year":"2020","journal-title":"Circ Cardiovasc Qual Outcomes"},{"key":"2026012114031394600_ehf213306-bib-0005","doi-asserted-by":"crossref","first-page":"541","DOI":"10.7326\/M19-3286","article-title":"Uses and limitations of the restricted mean survival time: illustrative examples from cardiovascular outcomes and mortality trials in type 2 diabetes","volume":"172","author":"Kloecker","year":"2020","journal-title":"Ann Intern Med"},{"key":"2026012114031394600_ehf213306-bib-0006","volume-title":"The advantages of restricted mean survival time in analysing Kaplan-Meier survival curves: analysis of 55 articles published in the last 12 months","author":"Messori"},{"key":"2026012114031394600_ehf213306-bib-0007","volume-title":"Eight major international journals have recently published a paper to the methodological advantages of the restricted mean survival time","author":"Messori"},{"key":"2026012114031394600_ehf213306-bib-0008","doi-asserted-by":"crossref","first-page":"1226","DOI":"10.1001\/jamacardio.2018.3957","article-title":"Estimated 5-year number needed to treat to prevent cardiovascular death or heart failure hospitalization with angiotensin receptor-neprilysin inhibition vs standard therapy for patients with heart failure with reduced ejection fraction: an analysis of data from the PARADIGM-HF trial","volume":"3","author":"Srivastava","year":"2018","journal-title":"JAMA Cardiol"},{"key":"2026012114031394600_ehf213306-bib-0009","volume-title":"Package \u201csurvRM2\u201d","author":"Uno","year":"2020"},{"key":"2026012114031394600_ehf213306-bib-0010","article-title":"The restricted mean survival time as a tool for ranking comparative outcomes in a narrative review that evaluates a network of randomised trials: an example based on PCSK9 inhibitors","author":"Messori","year":"2020","journal-title":"Am J Cardiovasc Drugs"},{"key":"2026012114031394600_ehf213306-bib-0011","first-page":"730","article-title":"Median versus mean lifetime survival in the analysis of survival data","volume":"82","author":"Messori","year":"1997","journal-title":"Haematologica"},{"key":"2026012114031394600_ehf213306-bib-0012","doi-asserted-by":"crossref","first-page":"993","DOI":"10.1056\/NEJMoa1409077","article-title":"Angiotensin-neprilysin inhibition versus enalapril in heart failure","volume":"371","author":"McMurray","year":"2014","journal-title":"N Engl J Med"},{"key":"2026012114031394600_ehf213306-bib-0013","doi-asserted-by":"crossref","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"}],"container-title":["ESC Heart Failure"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ehf2.13306","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ehf2.13306","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/eschf\/article-pdf\/8\/3\/2345\/65798244\/eschf_8_3_2345.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/eschf\/article-pdf\/8\/3\/2345\/65798244\/eschf_8_3_2345.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T19:03:23Z","timestamp":1769022203000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/eschf\/article\/8\/3\/2345\/8363485"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,17]]},"references-count":13,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2021,3,17]]},"published-print":{"date-parts":[[2021,6,1]]}},"URL":"https:\/\/doi.org\/10.1002\/ehf2.13306","relation":{},"ISSN":["2055-5822"],"issn-type":[{"value":"2055-5822","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2021,6]]},"published":{"date-parts":[[2021,3,17]]},"assertion":[{"value":"2020-07-23","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-03-02","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-03-17","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}