title: Safety and efficacy of LCZ696, a first-in-class angiotensin receptor neprilysin inhibitor, in Japanese patients with hypertension and renal dysfunction.
abstract: 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.
authors.affiliation: Division of Nephrology, Endocrinology and Vascular Medicine, Tohoku University Hospital, Miyagi, Japan.
authors.forename: Sadayoshi
authors.initials: S
authors.lastname: Ito
authors.affiliation: Kawasaki Medical School Hospital, Okayama, Japan.
authors.forename: Minoru
authors.initials: M
authors.lastname: Satoh
authors.affiliation: Novartis Pharma K.K., Tokyo, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Tamaki
authors.affiliation: Novartis Pharma K.K., Tokyo, Japan.
authors.forename: Hiromi
authors.initials: H
authors.lastname: Gotou
authors.affiliation: Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA.
authors.forename: Alan
authors.initials: A
authors.lastname: Charney
authors.affiliation: Novartis Pharma K.K., Tokyo, Japan.
authors.forename: Naoko
authors.initials: N
authors.lastname: Okino
authors.affiliation: Novartis Pharma K.K., Tokyo, Japan.
authors.forename: Mizuki
authors.initials: M
authors.lastname: Akahori
authors.affiliation: Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA.
authors.forename: Jack
authors.initials: J
authors.lastname: Zhang
mesh_terms: D000368:Aged; D000613:Aminobutyrates / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D057911:Angiotensin Receptor Antagonists / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D044466:Asian People; D001713:Biphenyl Compounds; D001794:Blood Pressure; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000188:drug therapy*; D007674:Kidney Diseases / Q000150:complications / Q000188:drug therapy*; D007677:Kidney Function Tests; D008297:Male; D008875:Middle Aged; D015260:Neprilysin / Q000037:antagonists & inhibitors*; D013777:Tetrazoles / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000068756:Valsartan
chemical_list: D000613:Aminobutyrates; D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents; D001713:Biphenyl Compounds; D004338:Drug Combinations; D013777:Tetrazoles; D000068756:Valsartan; D015260:Neprilysin; C549068:sacubitril and valsartan sodium hydrate drug combination