title: Long-term (52-week) safety and efficacy of Sacubitril/valsartan in Asian patients with hypertension.
abstract: Sacubitril/valsartan (LCZ696), a first-in-class angiotensin receptor-neprilysin inhibitor, demonstrated significant reductions in office and 24 h ambulatory blood pressure (BP) over 8 weeks in Asian patients with hypertension. This 52-week extension to the 8-week core study was aimed at evaluating the long-term safety, tolerability and efficacy of sacubitril/valsartan. Patients who completed an 8-week randomized study (the core study) were enrolled in this 52-week open-label study and received sacubitril/valsartan 200 mg QD. The sacubitril/valsartan dose was uptitrated to 400 mg QD if BP was uncontrolled (>140/90 mm Hg) after 4 weeks. Subsequently, in patients with uncontrolled BP, treatment was intensified every 4 weeks with amlodipine 5-10 mg followed by hydrochlorothiazide 6.25-25 mg. Of the 341 patients enrolled, 7 (2.1%) discontinued the study drug due to adverse events (AEs). The incidence of AEs and serious AEs were 63.9 and 3.8%, respectively, and no deaths were reported in this study. The most frequent AEs were nasopharyngitis (18.2%) and dizziness (8.8%). Events that were potentially indicative of low BP were infrequent. One patient reported mild transient angioedema (lasting 2.5 h) that resolved without treatment but led to study drug discontinuation. The sacubitril/valsartan-based regimen provided clinically significant mean sitting systolic BP (msSBP) and mean sitting diastolic BP (msDBP) reductions from baseline (-24.7/-16.2 mm Hg). The overall BP control, msSBP and msDBP response rates were 75.3, 90.6 and 87.6%, respectively. Long-term use of sacubitril/valsartan was generally safe and well-tolerated in patients with hypertension and provided significant BP reductions from baseline.
authors.affiliation: Department of Medicine, Division of Nephrology, General Clinical Research and Research Development Center, Phramongkutklao Hospital and College of Medicine, Bangkok, Thailand.
authors.forename: Ouppatham
authors.initials: O
authors.lastname: Supasyndh
authors.affiliation: Department of Cardiology, Peking University People's Hospital, Beijing, China.
authors.forename: Ningling
authors.initials: N
authors.lastname: Sun
authors.affiliation: Department of Medicine, Division of Cardiovascular Medicine, Jichi Medical University School of Medicine, Tochigi, Japan.
authors.forename: Kazuomi
authors.initials: K
authors.lastname: Kario
authors.affiliation: Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA.
authors.forename: Kudsia
authors.initials: K
authors.lastname: Hafeez
authors.affiliation: Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA.
authors.forename: Jack
authors.initials: J
authors.lastname: Zhang
mesh_terms: D000328:Adult; D000613:Aminobutyrates / Q000009:adverse effects* / Q000627:therapeutic use*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000009:adverse effects* / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000009:adverse effects* / Q000627:therapeutic use*; D044466:Asian People; D001713:Biphenyl Compounds; D001794:Blood Pressure; D004338:Drug Combinations; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology; D005260:Female; D006801:Humans; D006973:Hypertension / Q000188:drug therapy*; D015994:Incidence; D008297:Male; D008875:Middle Aged; D061214:Patient Safety; D013777:Tetrazoles / Q000009:adverse effects* / Q000627:therapeutic use*; D016896:Treatment Outcome; D000068756:Valsartan / Q000009:adverse effects* / Q000627:therapeutic use*
chemical_list: D000613:Aminobutyrates; D047228:Angiotensin II Type 1 Receptor Blockers; D000959:Antihypertensive Agents; D001713:Biphenyl Compounds; D004338:Drug Combinations; D013777:Tetrazoles; D000068756:Valsartan; C549068:sacubitril and valsartan sodium hydrate drug combination