TY - JOUR
T1 - Safety and efficacy of LCZ696, a first-in-class angiotensin receptor neprilysin inhibitor, in Japanese patients with hypertension and renal dysfunction
AU - Ito, Sadayoshi
AU - Satoh, Minoru
AU - Tamaki, Yuko
AU - Gotou, Hiromi
AU - Charney, Alan
AU - Okino, Naoko
AU - Akahori, Mizuki
AU - Zhang, Jack
N1 - Publisher Copyright:
© 2015 The Japanese Society of Hypertension All rights reserved.
Copyright:
Copyright 2015 Elsevier B.V., All rights reserved.
PY - 2015/4/9
Y1 - 2015/4/9
N2 - 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.
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.
KW - Japanese
KW - LCZ696
KW - angiotensin receptor neprilysin inhibitor
KW - renal dysfunction
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U2 - 10.1038/hr.2015.1
DO - 10.1038/hr.2015.1
M3 - Article
C2 - 25693859
AN - SCOPUS:84926664621
VL - 38
SP - 269
EP - 275
JO - Hypertension Research
JF - Hypertension Research
SN - 0916-9636
IS - 4
ER -