Mancia Giuseppe, Coca Antonio, Chazova Irina, Girerd Xavier, Haller Hermann, Pauletto Paolo, Pupek-Musialik Danuta, Svyshchenko Yevgeniya
aIRCSS, Istituto Auxologico Italiano and University Milano-Bicocca, Milan, Italy bHospital Clínic of Barcelona, University of Barcelona, Barcelona, Spain cInstitute of Clinical Cardiology, Department of Systemic Hypertension, Moscow, Russia dCardiovascular Prevention Unit, Hôpital de la Pitié Salpétrière, Paris, France eHannover Medical School, Department of Nephrology and Hypertension, Hannover, Germany fDepartment of Internal Medicine, University Hospital of Treviso & University of Padova, Padova, Italy gDepartment of Biochemistry and Molecular Biology, Karol Marcinkowski University of Medical Sciences, Poznan, Poland hStrazhesko Institute of Cardiology, Kiev, Ukraine.
J Hypertens. 2014 Aug;32(8):1700-7; discussion 1707. doi: 10.1097/HJH.0000000000000239.
The aim of this study was to evaluate the efficacy and safety of combinations of lercanidipine (L) and enalapril (E) at different doses on office and home blood pressure (BP) in patients with Stage 2 hypertension.
This was a randomized, double-blind, placebo-controlled, factorial study conducted in 100 centres from seven countries. Patients with office DBP 100-109 mmHg and home DBP at least 85 mmHg at the end of a 2-week placebo run-in period were randomized to a 10-week treatment with placebo, L (10 or 20 mg), E (10 or 20 mg) or the four L-E combinations. The efficacy parameters were office DBP at trough (primary), SBP at trough and home SBP and DBP. Office BP was measured at each visit in both the sitting and the standing position, while home BP was measured twice in the morning and twice in the evening for at least 3 days before treatment and at study end. Safety parameters included adverse events, laboratory tests and 12-lead ECG.
A total of 1039 patients were randomized (48% men, mean age 54 years, mean BMI 30 kg/m, 40% obese patients). Baseline BP was similar in all groups and lower for home than for office values (149/95 and 159/103 mmHg, respectively). A marked placebo effect was observed on office but not on home BP. Combination therapy was superior to placebo at all doses for both office and home BP. The greatest effect was observed in the L20/E20 group, in which the SBP/DBP fall amounted to -19.2/-15.2 and -13.2/-7.5 mmHg for sitting office and home BP, respectively. Similar reductions were observed on standing office BP. The L20/E20 combination was associated with less cough, palpitations and leg oedema than monotherapies, with no increased rate of dizziness or hypotension.
In Stage 2 hypertension, a fixed-dose combination of L and E ensures a control of both office and out-of-office BP, with a favourable tolerability profile.
本研究旨在评估不同剂量的乐卡地平（L）与依那普利（E）联合用药对2级高血压患者诊室血压和家庭血压的疗效及安全性。
这是一项在来自7个国家的100个中心进行的随机、双盲、安慰剂对照、析因研究。在为期2周的安慰剂导入期结束时，诊室舒张压为100 - 109 mmHg且家庭舒张压至少为85 mmHg的患者被随机分为接受安慰剂、L（10或20 mg）、E（10或20 mg）或四种L - E联合用药治疗10周。疗效参数为谷值时的诊室舒张压（主要指标）、谷值时的收缩压、家庭收缩压和舒张压。每次就诊时均测量坐位和立位的诊室血压，而在治疗前至少3天以及研究结束时，每天早晨和晚上测量两次家庭血压。安全性参数包括不良事件、实验室检查和12导联心电图。
共1039例患者被随机分组（男性占48%，平均年龄54岁，平均体重指数30 kg/m²，40%为肥胖患者）。所有组的基线血压相似，家庭血压低于诊室血压（分别为149/95和159/103 mmHg）。在诊室血压上观察到明显的安慰剂效应，但在家庭血压上未观察到。联合治疗在所有剂量下对诊室血压和家庭血压均优于安慰剂。在L20/E20组中观察到最大效应，其中坐位诊室血压和家庭血压的收缩压/舒张压降幅分别为 -19.2/-15.2和 -13.2/-7.5 mmHg。立位诊室血压也有类似降幅。与单药治疗相比，L20/E20联合用药引起的咳嗽、心悸和腿部水肿较少，头晕或低血压发生率未增加。
在2级高血压中，L与E的固定剂量联合用药可确保控制诊室血压和诊室外血压，且耐受性良好。
