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LCZ696, a First‐in‐Class Angiotensin Receptor‐Neprilysin Inhibitor: The First Clinical Experience in Patients With Severe Hypertension
Authors:Kazuomi Kario MD  PhD  Yuko Tamaki  Naoko Okino  Hiromi Gotou  Min Zhu MD  Jack Zhang MD  PhD
Affiliation:1. Jichi Medical University School of Medicine, Tochigi, Japan;2. Clinical Development, Novartis Pharma KK, Tokyo, Japan;3. Beijing Novartis Pharma Co. Ltd, Beijing, China;4. Novartis Pharmaceuticals Corporation, East Hanover, NJ
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.
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