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
Journal
Hypertension
Journal Volume
63
Journal Issue
4
Pages
698-705
Date Issued
2014
Author(s)
Kario K.
Sun N.
Supasyndh O.
Baek S.H.
Inubushi-Molessa A.
Zhang Y.
Gotou H.
Lefkowitz M.
Zhang J.
Abstract
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. ? 2014 American Heart Association, Inc.
Subjects
Asia; blood pressure monitoring ambulatory; hypertension; randomized controlled trial
SDGs
Other Subjects
3 (1 biphenyl 4 ylmethyl 3 ethoxycarbonyl 1 butylcarbamoyl)propionic acid plus valsartan; placebo; aged; ambulatory monitoring; arthralgia; article; Asian; atopic dermatitis; blood pressure monitoring; China; constipation; controlled study; cyst; dermal cyst; diarrhea; diastolic blood pressure; dizziness; double blind procedure; drug efficacy; drug safety; drug withdrawal; female; headache; hematuria; human; hypercholesterolemia; hyperglycemia; hyperlipidemia; hypertension; hyperuricemia; hypokalemia; Japan; Korea; major clinical study; male; multicenter study; pharyngitis; priority journal; pulse pressure; randomized controlled trial; rhinopharyngitis; risk assessment; single blind procedure; single drug dose; systolic blood pressure; Taiwan; Thailand; treatment duration; upper respiratory tract infection; Asia; blood pressure monitoring, ambulatory; hypertension; randomized controlled trial; Aged; Aminobutyrates; Angioedema; Angiotensin Receptor Antagonists; Asian Continental Ancestry Group; Blood Pressure; Blood Pressure Monitoring, Ambulatory; China; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Hypertension; Incidence; Japan; Male; Middle Aged; Neprilysin; Republic of Korea; Taiwan; Tetrazoles; Thailand; Treatment Outcome
Type
journal article