| Title: |
Initiating sacubitril/valsartan (LCZ696) in heart failure: results of TITRATION, a double-blind, randomized comparison of two uptitration regimens |
| Authors: |
Senni, Michele; McMurray, John J.V.; Wachter, Rolf; McIntyre, Hugh F.; Reyes, Antonio; Majercak, Ivan; Andreka, Peter; Shehova-Yankova, Nina; Anand, Inder; Yilmaz, Mehmet B.; Gogia, Harinder; Martinez-Selles, Manuel; Fischer, Steffen; Zilahi, Zsolt; Cosmi, Franco; Gelev, Valeri; Galve, Enrique; Gómez-Doblas, Juanjo J.; Nociar, Jan; Radomska, Maria; Sokolova, Beata; Volterrani, Maurizio; Sarkar, Arnab; Reimund, Bernard; Chen, Fabian; Charney, Alan |
| Publisher Information: |
Wiley |
| Publication Year: |
2016 |
| Collection: |
University of Glasgow: Enlighten - Publications |
| Description: |
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-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’. 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 ... |
| Document Type: |
article in journal/newspaper |
| File Description: |
text |
| Language: |
English |
| Relation: |
https://eprints.gla.ac.uk/120849/1/120849.pdf; Senni, M. et al. (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), pp. 1193-1202. (doi:10.1002/ejhf.548 ) (PMID:27170530) (PMCID:PMC5084812) |
| DOI: |
10.1002/ejhf.548 |
| Availability: |
https://eprints.gla.ac.uk/120849/; https://eprints.gla.ac.uk/120849/1/120849.pdf; https://doi.org/10.1002/ejhf.548 |
| Rights: |
cc_by_nc_nd_4 |
| Accession Number: |
edsbas.6D033707 |
| Database: |
BASE |