Efficacy and safety of LCZ696, a first-in-class angiotensin receptor neprilysin inhibitor, in Asian patients with hypertension: a randomized, double-blind, placebo-controlled study.
LCZ696 (Japanese adopted name: sucabitril valsartan sodium hydrate), a first-in-class angiotensin receptor neprilysin inhibitor, concomitantly inhibits neprilysin and blocks angiotensin type 1 receptor. This randomized, double-blind, placebo-controlled study, the first in Asia for this drug, evaluated the dose-related efficacy and safety of LCZ696 in patients with hypertension using 24-hour ambulatory blood pressure (BP) monitoring. Asian patients aged ≥18 years (n=389) with hypertension were randomized to receive LCZ696 100 mg (n=100), 200 mg (n=101), 400 mg (n=96), or placebo (n=92) for 8 weeks. The primary end point was mean difference across the 3 single-dose pairwise comparisons of LCZ696 versus placebo in clinic diastolic BP after 8-week treatment. Key secondary efficacy variables included changes in clinic systolic BP and pulse pressure and changes in 24-hour, daytime, and nighttime ambulatory BPs and pulse pressure. Safety assessments included recording all adverse events and serious adverse events. A total of 362 patients completed the study. Reductions in clinic systolic BP, diastolic BP (P<0.0001), and pulse pressure (P<0.001) were significantly greater with all doses of LCZ696 than with placebo. There were also significant reductions in 24-hour, daytime, and nighttime ambulatory systolic BP, diastolic BP, and pulse pressure for all doses of LCZ696 compared with placebo (P<0.0001). LCZ696 was well tolerated, and no cases of angioedema were reported. In conclusion, LCZ696 is effective for the treatment of hypertension in Asian population and, in general, is safe and well tolerated. Clinical Trial Information- URL: http://www.clinicaltrials.gov. Unique identifier: NCT01193101.
Division of Cardiovascular Medicine, Department of Medicine, Jichi Medical University School of Medicine, 3311-1, Yakushiji, Shimotsuke, Tochigi 329-0498, Japan. kkario@jichi.ac.jp.
Kazuomi
K
Kario
Ningling
N
Sun
Fu-Tien
FT
Chiang
Ouppatham
O
Supasyndh
Sang Hong
SH
Baek
Akiko
A
Inubushi-Molessa
Ying
Y
Zhang
Hiromi
H
Gotou
Martin
M
Lefkowitz
Jack
J
Zhang
D000368:Aged; D000613:Aminobutyrates / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D000799:Angioedema / Q000453:epidemiology; D057911:Angiotensin Receptor Antagonists / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D044466:Asian People; D001713:Biphenyl Compounds; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D018660:Blood Pressure Monitoring, Ambulatory; D002681:China; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004338:Drug Combinations; D005260:Female; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000208:ethnology* / Q000503:physiopathology; D015994:Incidence; D007564:Japan; D008297:Male; D008875:Middle Aged; D015260:Neprilysin / Q000037:antagonists & inhibitors*; D056910:Republic of Korea; D013624:Taiwan; D013777:Tetrazoles / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D013785:Thailand; D016896:Treatment Outcome; D000068756:Valsartan
D000613:Aminobutyrates; D057911:Angiotensin Receptor Antagonists; D001713:Biphenyl Compounds; D004338:Drug Combinations; D013777:Tetrazoles; D000068756:Valsartan; D015260:Neprilysin; C549068:sacubitril and valsartan sodium hydrate drug combination
Asia; blood pressure monitoring, ambulatory; hypertension; randomized controlled trial