{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T15:02:38Z","timestamp":1788447758155,"version":"build-2803163510"},"reference-count":30,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2025,11,12]],"date-time":"2025-11-12T00:00:00Z","timestamp":1762905600000},"content-version":"vor","delay-in-days":1149,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2022,9,20]],"date-time":"2022-09-20T00:00:00Z","timestamp":1663632000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Novartis Pharma AG"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2023,2,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Diabetes mellitus is associated with worse outcomes and lower attainment of disease-modifying therapies in patients with heart failure with reduced ejection fraction (HFrEF). This post hoc analysis of TRANSITION compared the patterns of tolerability and uptitration of sacubitril\/valsartan in patients with HFrEF stabilized after hospital admission due to acute decompensated HF depending on the presence or absence of diabetes as a co-morbidity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>TRANSITION, a randomized, open-label study compared sacubitril\/valsartan initiation pre-discharge vs. post-discharge (up to14 days) in 991 patients hospitalized for acutely decompensated HFrEF. The impact of diabetes status on tolerability and safety was studied at 10-week and 26-week post-randomization.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Among the 991 patients analysed at baseline, 460 (46.4%) had diabetes and exhibited a higher risk profile. At 10 weeks, sacubitril\/valsartan target dose (97\/103 mg bid) was achieved in a similar proportion of patients in each subgroup, when initiated pre-discharge or post-discharge respectively [diabetes subgroup: 47% (n = 105\/226) vs. 50% (n = 115\/228); relative risk ratio (RRR), 0.923; P = 0.412; non-diabetes subgroup: 45% (n = 119\/267) vs. 51% (n = 133\/261); RRR, 0.878; P = 0.155]. The proportions of patients achieving and maintaining either 49\/51 mg or 97\/103 mg bid [diabetes subgroup: 61.1% (n = 138\/226) vs. 67.5% (n = 154\/228); RRR, 0.909; P = 0.175; non-diabetes subgroup: 62.9% [n = 168\/267] vs 69.3% [n = 181\/261]; RRR, 0.906; P = 0.118] or any dose for \u22652 weeks leading to Week 10 [diabetes subgroup: 85% (n = 192\/226) vs. 88.2% (n = 201\/228); RRR, 0.966; P = 0.356; non-diabetes subgroup: 86.9% (n = 232\/267) vs. 90.8% (n = 237\/261); RRR, 0.963; P = 0.215] were also similar in each subgroup, when initiated pre-discharge or post-discharge, respectively. At 10 weeks, hypotension and renal dysfunction rates were similar, although hyperkalaemia was higher among patients with diabetes (15.9% vs. 9.5%). The rate of permanent discontinuation due to adverse events was similar in the diabetes and non-diabetes subgroups at 10 weeks, respectively: pre-discharge (7.5% vs. 7.1%) or post-discharge (5.7% vs. 4.2%). Similar patterns of uptitration and tolerability were observed at 26 weeks. Cardiac biomarkers including NT-proBNP (P &amp;lt; 0.005) and hs-TnT (P &amp;lt; 0.005) reduced significantly from baseline levels in both subgroups at Weeks 4 and 10; however, the response was greater among patients without diabetes. Mortality (diabetes vs. non-diabetes subgroups: 3.3% vs 4.0%; P = 0.438) and HF rehospitalization (diabetes vs. non-diabetes subgroups: 36.3% vs. 33.0%; P = 0.295) did not differ between the groups at 26 weeks.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Despite a higher risk profile among patients with diabetes, sacubitril\/valsartan initiation either before or shortly after discharge in hospitalized patients with HFrEF resulted in comparable rates of dose up-titration and tolerability as in those without diabetes.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ehf2.14166","type":"journal-article","created":{"date-parts":[[2022,9,20]],"date-time":"2022-09-20T07:58:57Z","timestamp":1663660737000},"page":"80-89","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Influence of Diabetes on Sacubitril\/Valsartan Titration and Clinical Outcomes in Patients Hospitalized for Heart Failure"],"prefix":"10.1093","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7146-7105","authenticated-orcid":false,"given":"Klaus K.","family":"Witte","sequence":"first","affiliation":[{"name":"Department of Internal Medicine I, University Hospital, RWTH Aachen University, Aachen, DE; and Leeds Institute of Cardio and Metabolic Medicine, University of Leeds , Leeds ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rolf","family":"Wachter","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Leipzig University Hospital , Leipzig ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michele","family":"Senni","sequence":"additional","affiliation":[{"name":"Cardiovascular Department & Cardiology Unit, Ospedale Papa Giovanni XXIII , Bergamo ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Belohlavek","sequence":"additional","affiliation":[{"name":"2nd Department of Medicine, Department of Cardiovascular Medicine, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague , Prague ,","place":["Czech Republic"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ewa","family":"Straburzynska-Migaj","sequence":"additional","affiliation":[{"name":"1st Department of Cardiology, Poznan University of Medical Sciences , Poznan ,","place":["Poland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Candida","family":"Fonseca","sequence":"additional","affiliation":[{"name":"Hospital de Sao Francisco Xavier , Lisbon ,","place":["Portugal"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Lonn","sequence":"additional","affiliation":[{"name":"Department of Medicine and Population Health Research Institute, McMaster University , Hamilton ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adele","family":"No\u00e8","sequence":"additional","affiliation":[{"name":"Cardio Renal and Metabolic Department, Novartis Pharma AG , Basel ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heike","family":"Schwende","sequence":"additional","affiliation":[{"name":"Cardio Renal and Metabolic Department, Novartis Pharma AG , Basel ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dmytro","family":"Butylin","sequence":"additional","affiliation":[{"name":"Cardio Renal and Metabolic Department, Novartis Pharma AG , Basel ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"YannTong","family":"Chiang","sequence":"additional","affiliation":[{"name":"Cardio, Renal and Metabolic Department, Novartis Pharmaceuticals , East Hanover, NJ ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Domingo","family":"Pascual-Figal","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Hospital Virgen de la Arrixaca, University of Murcia, Murcia, Spain & Centro Nacional de Investigaciones Cardiovasculares (CNIC) , Madrid ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"the TRANSITION investigators","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,9,20]]},"reference":[{"key":"2026012114122119100_ehf214166-bib-0001","doi-asserted-by":"crossref","first-page":"853","DOI":"10.1002\/ejhf.1170","article-title":"Type 2 diabetes mellitus and heart failure: A position statement from the heart failure Association of the European Society of cardiology","volume":"20","author":"Seferovic","year":"2018","journal-title":"Eur J Heart 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