RT Journal Article
T1 Initiating sacubitril/valsartan (LCZ696) in heart failure: results of TITRATION, a double-blind, randomized comparison of two uptitration regimens.
A1 Senni, Michele
A1 McMurray, John J V
A1 Wachter, Rolf
A1 McIntyre, Hugh F
A1 Reyes, Antonio
A1 Majercak, Ivan
A1 Andreka, Peter
A1 Shehova-Yankova, Nina
A1 Anand, Inder
A1 Yilmaz, Mehmet B
A1 Gogia, Harinder
A1 Martinez-Selles, Manuel
A1 Fischer, Steffen
A1 Zilahi, Zsolt
A1 Cosmi, Franco
A1 Gelev, Valeri
A1 Galve, Enrique
A1 Gómez-Doblas, Juanjo J
A1 Nociar, Jan
A1 Radomska, Maria
A1 Sokolova, Beata
A1 Volterrani, Maurizio
A1 Sarkar, Arnab
A1 Reimund, Bernard
A1 Chen, Fabian
A1 Charney, Alan
K1 ARNI
K1 Heart failure
K1 LCZ696
K1 Sacubitril
K1 Tolerability
K1 Valsartan
AB To assess 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 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.
YR 2016
FD 2016-05-12
LK http://hdl.handle.net/10668/10075
UL http://hdl.handle.net/10668/10075
LA en
DS RISalud
RD Apr 8, 2025