Wang Ji-Guang, Yukisada Kimihiko, Sibulo Antonio, Hafeez Kudsia, Jia Yan, Zhang Jack
aDepartment of Hypertension, Centre for Epidemiological Studies and Clinical Trials, Shanghai Key Lab of Hypertension, The Shanghai Institute of Hypertension, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China bYukisada Internal Medicine, Tokyo, Japan cSt. Luke's Medical Center, Quezon City, Philippines dNovartis Pharmaceuticals Corporation, East Hanover, New Jersey, USA.
J Hypertens. 2017 Apr;35(4):877-885. doi: 10.1097/HJH.0000000000001219.
The objective of this study is to evaluate the efficacy and safety of sacubitril/valsartan (LCZ696, an angiotensin receptor and neprilysin inhibitor) add-on to amlodipine compared with amlodipine monotherapy in Asian patients with systolic hypertension uncontrolled with amlodipine.
Patients with mean clinic SBP at least 145 mmHg and less than 180 mmHg after a 4-week treatment with amlodipine 5 mg/day were randomized to receive LCZ696/amlodipine (200/5 mg/day) or amlodipine 5 mg/day for 8 weeks. The primary assessment was the superiority of LCZ696/amlodipine versus amlodipine in lowering 24-h ambulatory SBP from baseline to week 8. Secondary assessments included 24-h ambulatory DBP and pulse pressure (PP), daytime and night-time BP, clinic BP and PP, BP control/responder rate (<140/90 mmHg or a reduction ≥20/10 mmHg from baseline), and safety.
Of the 371 patients screened, 266 (71.7%) patients (mean age 55.4 years; 24-h SBP/DBP 139.0/86.1 mmHg at baseline) who did not respond to 4-week treatment with amlodipine 5 mg/day were randomized. At week 8, LCZ696/amlodipine provided greater reductions in 24-h SBP compared with amlodipine monotherapy from baseline (-13.9 versus -0.8 mmHg, P < 0.001). All the secondary efficacy assessments were significantly (P < 0.001) in favour of LCZ696/amlodipine, for instance, 24-h PP (-5.8 versus -0.6 mmHg). Overall, the incidence of adverse events was 20.0% with LCZ696/amlodipine and 21.3% with amlodipine.
LCZ696/amlodipine showed significantly greater 24-h ambulatory BP and PP reductions compared with amlodipine monotherapy. Both treatments were generally well tolerated. Therefore, LCZ696/amlodipine combination could be an effective treatment for patients with systolic hypertension uncontrolled with amlodipine.
本研究旨在评估在接受氨氯地平治疗但收缩压仍未得到控制的亚洲患者中，与氨氯地平单药治疗相比，添加沙库巴曲缬沙坦（LCZ696，一种血管紧张素受体和中性肽链内切酶抑制剂）至氨氯地平治疗的疗效和安全性。
在接受每日5毫克氨氯地平治疗4周后，诊室平均收缩压至少为145毫米汞柱且低于180毫米汞柱的患者被随机分组，分别接受LCZ696/氨氯地平（每日200/5毫克）或每日5毫克氨氯地平治疗8周。主要评估指标是从基线到第8周，LCZ696/氨氯地平与氨氯地平相比在降低24小时动态收缩压方面的优越性。次要评估指标包括24小时动态舒张压和脉压（PP）、日间和夜间血压、诊室血压和PP、血压控制/达标率（<140/90毫米汞柱或较基线降低≥20/10毫米汞柱）以及安全性。
在371例筛查患者中，266例（71.7%）对每日5毫克氨氯地平治疗4周无反应的患者（平均年龄55.4岁；基线时24小时收缩压/舒张压为139.0/86.1毫米汞柱）被随机分组。在第8周时，与氨氯地平单药治疗相比，LCZ696/氨氯地平使24小时收缩压从基线时的降幅更大（-13.9对-0.8毫米汞柱，P<0.001）。所有次要疗效评估指标均显著（P<0.001）有利于LCZ696/氨氯地平，例如24小时脉压（-5.8对-0.6毫米汞柱）。总体而言，LCZ696/氨氯地平组不良事件发生率为20.0%，氨氯地平组为21.3%。
与氨氯地平单药治疗相比，LCZ696/氨氯地平使24小时动态血压和脉压的降幅显著更大。两种治疗的耐受性总体良好。因此，LCZ696/氨氯地平联合用药可能是治疗氨氯地平控制不佳的收缩期高血压患者的有效疗法。
