title: LCZ696, a First-in-Class Angiotensin Receptor-Neprilysin Inhibitor: The First Clinical Experience in Patients With Severe Hypertension.
abstract: The safety of LCZ696, a novel angiotensin receptor-neprilysin inhibitor, was evaluated for the first time in patients with severe hypertension in this 8-week, multicenter, open-label study. Thirty-five Japanese patients with either office systolic blood pressure (SBP) ≥180 mm Hg or diastolic blood pressure (DBP) ≥110 mm Hg received LCZ696 200 mg. If blood pressure was uncontrolled, the LCZ696 dose was increased to 400 mg after 2 weeks (if there were no safety concerns; n=32), followed by an optional addition of another antihypertensive drug (except angiotensin receptor blocker and angiotensin-converting enzyme inhibitor) after 4 weeks (n=21). Reductions in office SBP/DBP (baseline, 173.4 mm Hg/112.4 mm Hg) and pulse pressure (baseline, 61.0 mm Hg) at week 8 were 35.3/22.1 mm Hg and 13.2 mm Hg, respectively. The overall incidence of adverse events was 48.6% with no reports of dizziness, hypotension, or angioedema. The LCZ696-based regimen was generally well-tolerated and could present a treatment option for severe hypertension in Asian patients especially in reducing SBP and pulse pressure.
authors.affiliation: Jichi Medical University School of Medicine, Tochigi, Japan.
authors.forename: Kazuomi
authors.initials: K
authors.lastname: Kario
authors.affiliation: Clinical Development, Novartis Pharma KK, Tokyo, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Tamaki
authors.affiliation: Clinical Development, Novartis Pharma KK, Tokyo, Japan.
authors.forename: Naoko
authors.initials: N
authors.lastname: Okino
authors.affiliation: Clinical Development, Novartis Pharma KK, Tokyo, Japan.
authors.forename: Hiromi
authors.initials: H
authors.lastname: Gotou
authors.affiliation: Beijing Novartis Pharma Co. Ltd, Beijing, China.
authors.forename: Min
authors.initials: M
authors.lastname: Zhu
authors.affiliation: Novartis Pharmaceuticals Corporation, East Hanover, NJ.
authors.forename: Jack
authors.initials: J
authors.lastname: Zhang
mesh_terms: D000368:Aged; D000613:Aminobutyrates / Q000008:administration & dosage*; D057911:Angiotensin Receptor Antagonists / Q000008:administration & dosage; D001713:Biphenyl Compounds; D001794:Blood Pressure / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004338:Drug Combinations; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D015260:Neprilysin / Q000037:antagonists & inhibitors*; D012720:Severity of Illness Index; D013777:Tetrazoles / Q000008:administration & dosage*; D013997:Time Factors; D016896:Treatment Outcome; D000068756:Valsartan
chemical_list: 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