{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T11:39:08Z","timestamp":1771933148046,"version":"3.50.1"},"reference-count":10,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2021,7,1]],"date-time":"2021-07-01T00:00:00Z","timestamp":1625097600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["European J of Heart Fail"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>The 4822 patients randomized in the PARAGON\u2010HF trial were a subset of 5746 initially eligible patients who entered sequential run\u2010in periods. We identified patient factors associated with study discontinuation during the run\u2010in period and estimated the implications of these discontinuations for the overall study result.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>We utilized multivariable logistic regression models to identify patient factors associated with study discontinuation during the run\u2010in period. The efficacy of sacubitril\/valsartan in a broader cohort approximating the full run\u2010in population was estimated by weighting randomized patients according to the inverse probability of run\u2010in completion. A total of 924 (16.1%) subjects failed to complete the run\u2010in period. In multivariable models, non\u2010completion was associated with region other than Central Europe, lower systolic blood pressure, lower serum sodium, lower haemoglobin, lower estimated glomerular filtration rate, higher N\u2010terminal pro\u2010B\u2010type natriuretic peptide, higher New York Heart Association functional class, prior heart failure (HF) hospitalization, and lack of prior use of renin\u2013angiotensin system inhibitors or beta\u2010blocker. In repeat analysis of the effect of randomized treatment in PARAGON\u2010HF giving greater weight to participants resembling those who failed to complete the run\u2010in period, the incidence of HF hospitalizations and cardiovascular death was higher, and sacubitril\/valsartan treatment reduced the composite of total HF hospitalizations and cardiovascular death compared with valsartan (rate ratio 0.86; 95% confidence interval 0.74\u20131.00).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Patients with more advanced HF were at higher risk for non\u2010completion of the run\u2010in period in PARAGON\u2010HF. Re\u2010analysis of study outcomes accounting for the effect of run\u2010in non\u2010completion did not alter the estimated treatment effects of sacubitril\/valsartan vs. valsartan.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ejhf.2262","type":"journal-article","created":{"date-parts":[[2021,6,11]],"date-time":"2021-06-11T05:08:23Z","timestamp":1623388103000},"page":"2085-2090","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Influence of study discontinuation during the run\u2010in period on the estimated efficacy of sacubitril\/valsartan in the\n                    <scp>PARAGON\u2010HF<\/scp>\n                    trial"],"prefix":"10.1093","volume":"23","author":[{"given":"Kota","family":"Suzuki","sequence":"first","affiliation":[{"name":"Division of Cardiovascular Medicine Brigham and Women's Hospital  Boston MA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brian","family":"Claggett","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine Brigham and Women's Hospital  Boston MA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masatoshi","family":"Minamisawa","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine Brigham and Women's Hospital  Boston MA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Milton","family":"Packer","sequence":"additional","affiliation":[{"name":"Baylor Heart and Vascular Institute Baylor University Medical Center  Dallas TX USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael R.","family":"Zile","sequence":"additional","affiliation":[{"name":"Ralph H. Johnson Department of Veterans Affairs Medical Center  Charleston SC USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marc A.","family":"Pfeffer","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine Brigham and Women's Hospital  Boston MA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lu\u2010May","family":"Chiang","sequence":"additional","affiliation":[{"name":"Novartis Pharmaceuticals  East Hanover NJ USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin","family":"Lefkowitz","sequence":"additional","affiliation":[{"name":"Novartis Pharmaceuticals  East Hanover NJ USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John J.V.","family":"McMurray","sequence":"additional","affiliation":[{"name":"BHF Cardiovascular Research Centre University of Glasgow  Glasgow UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Scott D.","family":"Solomon","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine Brigham and Women's Hospital  Boston MA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Akshay S.","family":"Desai","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine Brigham and Women's Hospital  Boston MA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2021,7]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1908655"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.279.3.222"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/1467-9868.00259"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCHEARTFAILURE.115.002735"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCHEARTFAILURE.118.004962"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(99)04440-2"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199108013250501"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199605233342101"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2012.14795"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.120.018104"}],"container-title":["European Journal of Heart Failure"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ejhf.2262","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ejhf.2262","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ejhf.2262","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,6]],"date-time":"2026-01-06T12:15:13Z","timestamp":1767701713000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ejhf.2262"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7]]},"references-count":10,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2021,12]]}},"alternative-id":["10.1002\/ejhf.2262"],"URL":"https:\/\/doi.org\/10.1002\/ejhf.2262","archive":["Portico"],"relation":{},"ISSN":["1388-9842","1879-0844"],"issn-type":[{"value":"1388-9842","type":"print"},{"value":"1879-0844","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,7]]},"assertion":[{"value":"2020-12-26","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-06-05","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-07-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}