Wang Tzung-Dau, Tan Ru-San, Lee Hae-Young, Ihm Sang-Hyun, Rhee Moo-Yong, Tomlinson Brian, Pal Parasar, Yang Fan, Hirschhorn Elizabeth, Prescott Margaret F, Hinder Markus, Langenickel Thomas H
From the Cardiovascular Center and Division of Cardiology, Department of Internal Medicine, National Taiwan University Hospital, Taipei City, Taiwan (T.-D.W.); National Heart Centre, Department of Cardiology, Singapore (R.-S.T.); Seoul National University Hospital, Department of Internal Medicine, South Korea (H.-Y.L.); The Catholic University of Korea Bucheon, St Mary's Hospital, Department of Cardiology, Bucheon-si, Gyeonggi-do, South Korea (S.-H.I.); Dongguk University Ilsan Hospital, Cardiovascular Center, Goyang-si, Gyeonggi-do, South Korea (M.-Y.R.); The Chinese University of Hong Kong, Department of Medicine & Therapeutics, Shatin, NT (B.T.); Novartis Healthcare Private Limited, Biostatistical Sciences, Hyderabad, India (P.P.); Novartis Institutes for Biomedical Research, Translational Medicine, Beijing, China (F.Y.); Novartis Institutes for Biomedical Research, Inc, Translational Medicine, Cambridge, MA (E.H.); Novartis Pharmaceuticals Corporation, Global Clinical Development, East Hannover, NJ (M.F.P.); and Novartis Pharma AG, Translational Medicine, Basel, Switzerland (M.H., T.H.L.).
Hypertension. 2017 Jan;69(1):32-41. doi: 10.1161/HYPERTENSIONAHA.116.08484. Epub 2016 Nov 14.
Salt-sensitive hypertension (SSH) is characterized by impaired sodium excretion and subnormal vasodilatory response to salt loading. Sacubitril/valsartan (LCZ696) was hypothesized to increase natriuresis and diuresis and result in superior blood pressure control compared with valsartan in Asian patients with SSH. In this randomized, double-blind, crossover study, 72 patients with SSH received sacubitril/valsartan 400 mg and valsartan 320 mg once daily for 4 weeks each. SSH was diagnosed if the mean arterial pressure increased by ≥10% when patients switched from low (50 mmol/d) to high (320 mmol/d) sodium diet. The primary outcome was cumulative 6- and 24-hour sodium excretion after first dose administration. Compared with valsartan, sacubitril/valsartan was associated with a significant increase in natriuresis (adjusted treatment difference: 24.5 mmol/6 hours, 50.3 mmol/24 hours, both P<0.001) and diuresis (adjusted treatment difference: 291.2 mL/6 hours, P<0.001; 356.4 mL/24 hours, P=0.002) on day 1, but not on day 28, and greater reductions in office and ambulatory blood pressure on day 28. Despite morning dosing of both drugs, ambulatory blood pressure reductions were more pronounced at nighttime than at daytime or the 24-hour average. Compared with valsartan, sacubitril/valsartan significantly reduced N-terminal pro B-type natriuretic peptide levels on day 28 (adjusted treatment difference: -20%; P=0.001). Sacubitril/valsartan and valsartan were safe and well tolerated with no significant changes in body weight or serum sodium and potassium levels with either treatments. In conclusion, sacubitril/valsartan compared with valsartan was associated with short-term increases in natriuresis and diuresis, superior office and ambulatory blood pressure control, and significantly reduced N-terminal pro B-type natriuretic peptide levels in Asian patients with SSH.
URL: http://www.clinicaltrials.gov. Unique identifier: NCT01681576.
盐敏感性高血压（SSH）的特征是钠排泄受损以及对盐负荷的血管舒张反应低于正常水平。研究假设，与缬沙坦相比，沙库巴曲缬沙坦（LCZ696）可增加尿钠排泄和利尿作用，并能更好地控制亚洲SSH患者的血压。在这项随机、双盲、交叉研究中，72例SSH患者分别接受沙库巴曲缬沙坦400mg和缬沙坦320mg治疗，每日1次，各治疗4周。当患者从低钠（50mmol/d）饮食转为高钠（320mmol/d）饮食时，若平均动脉压升高≥10%，则诊断为SSH。主要结局是首次给药后6小时和24小时的累积尿钠排泄量。与缬沙坦相比，沙库巴曲缬沙坦在第1天可显著增加尿钠排泄（校正治疗差异：24.5mmol/6小时，50.3mmol/24小时，P均<0.001）和利尿作用（校正治疗差异：291.2mL/6小时，P<0.001；356.4mL/24小时，P=0.002），但在第28天无此作用，且在第28天可更大程度地降低诊室血压和动态血压。尽管两种药物均在早晨给药，但动态血压在夜间的降低幅度比白天或24小时平均值更为明显。与缬沙坦相比，沙库巴曲缬沙坦在第28天可显著降低N末端B型利钠肽前体水平（校正治疗差异：-20%；P=0.001）。沙库巴曲缬沙坦和缬沙坦安全性良好，耐受性佳，两种治疗方式对体重、血清钠和钾水平均无显著影响。总之，与缬沙坦相比，沙库巴曲缬沙坦可使亚洲SSH患者短期尿钠排泄和利尿作用增加，更好地控制诊室血压和动态血压，并显著降低N末端B型利钠肽前体水平。
