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10.1002/ejhf.548

http://scihub22266oqcxt.onion/10.1002/ejhf.548
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suck abstract from ncbi


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pmid27170530
      Eur+J+Heart+Fail 2016 ; 18 (9 ): 1193-202
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  • 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.
  • |Aged [MESH]
  • |Aminobutyrates/*administration & dosage [MESH]
  • |Angiotensin Receptor Antagonists/*administration & dosage [MESH]
  • |Biphenyl Compounds [MESH]
  • |Double-Blind Method [MESH]
  • |Drug Combinations [MESH]
  • |Female [MESH]
  • |Heart Failure/*drug therapy [MESH]
  • |Humans [MESH]
  • |Hyperkalemia/chemically induced [MESH]
  • |Hypotension/chemically induced [MESH]
  • |Male [MESH]
  • |Middle Aged [MESH]
  • |Neprilysin/*antagonists & inhibitors [MESH]
  • |Renal Insufficiency/chemically induced [MESH]
  • |Tetrazoles/*administration & dosage [MESH]
  • |Treatment Outcome [MESH]


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