Initiating sacubitril/valsartan (LCZ696) in heart failure: results of TITRATION, a double-blind, randomized comparison of two uptitration regimens

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dc.contributor.author Senni, M.
dc.contributor.author McMurray, John J. V.
dc.contributor.author Wachter, R.
dc.contributor.author McIntyre, H. F.
dc.contributor.author Reyes, A.
dc.contributor.author Majercak, I.
dc.contributor.author Andreka, P.
dc.contributor.author Shehova-Yankova, Nina
dc.contributor.author Anand, I.
dc.contributor.author Yilmaz, M. B.
dc.contributor.author Gogia, H.
dc.contributor.author Martínez Sellés Oliveria Soares, Manuel
dc.contributor.author Fischer, S.
dc.contributor.author Zilahi, Z.
dc.contributor.author Cosmi, F.
dc.contributor.author Gelev, V.
dc.contributor.author Galve Basilio, Enrique
dc.contributor.author Gómez Doblas, J. J.
dc.contributor.author Nociar, J.
dc.contributor.author Radomska, M.
dc.contributor.author Sokolova, B.
dc.contributor.author Volterrani, M.
dc.contributor.author Sarkar, A.
dc.contributor.author Reimund, B.
dc.contributor.author Chen, F.
dc.contributor.author Charney, A.
dc.date.accessioned 2016-12-14T11:21:11Z
dc.date.available 2016-12-14T11:21:11Z
dc.date.issued 2016
dc.identifier.citation Senni, M., McMurray, J. J., Wachter, R., McIntyre, H. F., Reyes, A., Majercak, I., ... & Gogia, H. (2016). Initiating sacubitril/valsartan (LCZ696) in heart failure: results of TITRATION, a double‐blind, randomized comparison of two uptitration regimens. European journal of heart failure, 18(9), 1193–1202. DOI: 10.1002/ejhf.548 spa
dc.identifier.issn 13889842
dc.identifier.issn 18790844
dc.identifier.uri http://hdl.handle.net/11268/6090
dc.description.abstract The aim is tassess the tolerability of initiating/uptitrating sacubitril/valsartan (LCZ696) from 50 to 200 mg twice daily (target dose) over 3 and 6 weeks in heart failure (HF) patients (ejection fraction ≤35%). A 5-day open-label run-in (sacubitril/valsartan 50 mg twice daily) preceded an 11-week, double-blind, randomization period [100 mg twice daily for 2 weeks followed by 200 mg twice daily (‘condensed’ regimen) vs. 50 mg twice daily for 2 weeks, 100 mg twice daily for 3 weeks, followed by 200 mg twice daily (‘conservative’ regimen)]. Patients were stratified by pre-study dose of angiotensin-converting enzyme inhibitor/angiotensin-receptor blocker (ACEI/ARB; low-dose stratum included ACEI/ARB-naïve patients). Of 540 patients entering run-in, 498 (92%) were randomized and 429 (86.1% of randomized) completed the study. Pre-defined tolerability criteria were hypotension, renal dysfunction and hyperkalaemia; and adjudicated angioedema, which occurred in (‘condensed’ vs. ‘conservative’) 9.7% vs. 8.4% (P = 0.570), 7.3% vs. 7.6% (P = 0.990), 7.7% vs. 4.4% (P = 0.114), and 0.0% vs. 0.8% of patients, respectively. Corresponding proportions for pre-defined systolic blood pressure <95 mmHg, serum potassium >5.5 mmol/L, and serum creatinine >3.0 mg/dL were 8.9% vs. 5.2% (P = 0.102), 7.3% vs. 4.0% (P = 0.097), and 0.4% vs. 0%, respectively. In total, 378 (76%) patients achieved and maintained sacubitril/valsartan 200 mg twice daily without dose interruption/down-titration over 12 weeks (77.8% vs. 84.3% for ‘condensed’ vs. ‘conservative’; P = 0.078). Rates by ACEI/ARB pre-study dose stratification were 82.6% vs. 83.8% (P = 0.783) for high-dose/‘condensed’ vs. high-dose/‘conservative’ and 84.9% vs. 73.6% (P = 0.030) for low-dose/‘conservative’ vs. low-dose/‘condensed’. Initiation/uptitration of sacubitril/valsartan from 50 to 200 mg twice daily over 3 or 6 weeks had a tolerability profile in line with other HF treatments. More gradual initiation/uptitration maximized attainment of target dose in the low-dose ACEI/ARB group. spa
dc.description.sponsorship Novartis Pharmaceuticals Corporation, USA spa
dc.language.iso eng spa
dc.rights Reconocimiento-NoComercial-SinObraDerivada 4.0 Internacional *
dc.rights.uri https://creativecommons.org/licenses/by-nc-nd/4.0/deed.es_ES *
dc.title Initiating sacubitril/valsartan (LCZ696) in heart failure: results of TITRATION, a double-blind, randomized comparison of two uptitration regimens spa
dc.type article spa
dc.description.impact 6.968 JCR (2016) Q1, 11/126 Cardiac and Cardiovascular Systems spa
dc.identifier.doi 10.1002/ejhf.548
dc.rights.accessRights openAccess spa
dc.subject.uem Insuficiencia cardíaca spa
dc.subject.uem Corazón - Enfermedades spa
dc.subject.unesco Enfermedad cardiovascular spa
dc.description.filiation UEM spa
dc.peerreviewed Si spa

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Reconocimiento-NoComercial-SinObraDerivada 4.0 Internacional Except where otherwise noted, this item's license is described as Reconocimiento-NoComercial-SinObraDerivada 4.0 Internacional