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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Eur+J+Heart+Fail
2016 ; 18
(9
): 1193-202
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English Wikipedia
Initiating sacubitril/valsartan (LCZ696) in heart failure: results of TITRATION,
a double-blind, randomized comparison of two uptitration regimens
#MMPMID27170530
Senni M
; McMurray JJ
; Wachter R
; McIntyre HF
; Reyes A
; Majercak I
; Andreka P
; Shehova-Yankova N
; Anand I
; Yilmaz MB
; Gogia H
; Martinez-Selles M
; Fischer S
; Zilahi Z
; Cosmi F
; Gelev V
; Galve E
; Gómez-Doblas JJ
; Nociar J
; Radomska M
; Sokolova B
; Volterrani M
; Sarkar A
; Reimund B
; Chen F
; Charney A
Eur J Heart Fail
2016[Sep]; 18
(9
): 1193-202
PMID27170530
show ga
AIMS: 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%). METHODS AND RESULTS: 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-naďve 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'. CONCLUSIONS:
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.