PMID- 25693859
OWN - NLM
STAT- MEDLINE
DCOM- 20151229
LR  - 20221207
IS  - 1348-4214 (Electronic)
IS  - 0916-9636 (Print)
IS  - 0916-9636 (Linking)
VI  - 38
IP  - 4
DP  - 2015 Apr
TI  - Safety and efficacy of LCZ696, a first-in-class angiotensin receptor neprilysin 
      inhibitor, in Japanese patients with hypertension and renal dysfunction.
PG  - 269-75
LID - 10.1038/hr.2015.1 [doi]
AB  - This 8-week, multi-center, open-label study assessed the safety and efficacy of 
      LCZ696, a first-in-class angiotensin receptor neprilysin inhibitor, in Japanese 
      patients with hypertension and renal dysfunction. Patients (n=32) with mean 
      sitting systolic blood pressure (msSBP) ⩾140 mm Hg (after a 2-5-week washout of 
      previous antihypertensive medications) and estimated glomerular filtration rate 
      (eGFR) ⩾15 and <60 ml min(-1) 1.73 m(-2) received LCZ696 100 mg with an optional 
      titration to 200 and 400 mg in a sequential manner starting from Week 2 in 
      patients with inadequate BP control (msSBP ⩾130 mm Hg and mean sitting diastolic 
      blood pressure (msDBP) ⩾80 mm Hg) and without safety concerns. Safety was 
      assessed by monitoring and recording all adverse events (AEs) and change in 
      potassium and creatinine. Efficacy was assessed as change from baseline in 
      msSBP/msDBP. The mean baseline BP was 151.6/86.9 mm Hg, urinary 
      albumin/creatinine ratio (UACR) geometric mean was 7.3 mg mmol(-1) and eGFR was 
      ⩾30 and <60 in 25 (78.1%) patients and was ⩾15 and <30 in 7 (21.9%) patients. 
      Fourteen (43.8%) patients reported at least one AE, which were mild in severity. 
      No severe AEs or deaths were reported. There were no clinically meaningful 
      changes in creatinine, potassium, blood urea nitrogen and eGFR. The geometric 
      mean reduction in UACR was 15.1%, and the mean reduction in msSBP and msDBP was 
      20.5+/-11.3 and 8.3+/-6.3 mm Hg, respectively, from baseline to Week 8 end point. 
      LCZ696 was generally safe and well tolerated and showed effective BP reduction in 
      Japanese patients with hypertension and renal dysfunction without a decline in 
      renal function.
FAU - Ito, Sadayoshi
AU  - Ito S
AD  - Division of Nephrology, Endocrinology and Vascular Medicine, Tohoku University 
      Hospital, Miyagi, Japan.
FAU - Satoh, Minoru
AU  - Satoh M
AD  - Kawasaki Medical School Hospital, Okayama, Japan.
FAU - Tamaki, Yuko
AU  - Tamaki Y
AD  - Novartis Pharma K.K., Tokyo, Japan.
FAU - Gotou, Hiromi
AU  - Gotou H
AD  - Novartis Pharma K.K., Tokyo, Japan.
FAU - Charney, Alan
AU  - Charney A
AD  - Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA.
FAU - Okino, Naoko
AU  - Okino N
AD  - Novartis Pharma K.K., Tokyo, Japan.
FAU - Akahori, Mizuki
AU  - Akahori M
AD  - Novartis Pharma K.K., Tokyo, Japan.
FAU - Zhang, Jack
AU  - Zhang J
AD  - Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA.
LA  - eng
PT  - Clinical Trial, Phase III
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20150219
PL  - England
TA  - Hypertens Res
JT  - Hypertension research : official journal of the Japanese Society of Hypertension
JID - 9307690
RN  - 0 (Aminobutyrates)
RN  - 0 (Angiotensin Receptor Antagonists)
RN  - 0 (Antihypertensive Agents)
RN  - 0 (Biphenyl Compounds)
RN  - 0 (Drug Combinations)
RN  - 0 (Tetrazoles)
RN  - 80M03YXJ7I (Valsartan)
RN  - EC 3.4.24.11 (Neprilysin)
RN  - WB8FT61183 (sacubitril and valsartan sodium hydrate drug combination)
SB  - IM
MH  - Aged
MH  - Aminobutyrates/*adverse effects/pharmacokinetics/*therapeutic use
MH  - Angiotensin Receptor Antagonists/*therapeutic use
MH  - Antihypertensive Agents/*adverse effects/pharmacokinetics/*therapeutic use
MH  - Asian People
MH  - Biphenyl Compounds
MH  - Blood Pressure
MH  - Dose-Response Relationship, Drug
MH  - Drug Combinations
MH  - Female
MH  - Glomerular Filtration Rate
MH  - Humans
MH  - Hypertension/complications/*drug therapy
MH  - Kidney Diseases/complications/*drug therapy
MH  - Kidney Function Tests
MH  - Male
MH  - Middle Aged
MH  - Neprilysin/*antagonists & inhibitors
MH  - Tetrazoles/*adverse effects/pharmacokinetics/*therapeutic use
MH  - Valsartan
PMC - PMC4396400
EDAT- 2015/02/20 06:00
MHDA- 2015/12/30 06:00
PMCR- 2015/04/14
CRDT- 2015/02/20 06:00
PHST- 2014/06/25 00:00 [received]
PHST- 2014/12/16 00:00 [revised]
PHST- 2014/12/23 00:00 [accepted]
PHST- 2015/02/20 06:00 [entrez]
PHST- 2015/02/20 06:00 [pubmed]
PHST- 2015/12/30 06:00 [medline]
PHST- 2015/04/14 00:00 [pmc-release]
AID - hr20151 [pii]
AID - 10.1038/hr.2015.1 [doi]
PST - ppublish
SO  - Hypertens Res. 2015 Apr;38(4):269-75. doi: 10.1038/hr.2015.1. Epub 2015 Feb 19.