乐卡地平与依那普利联合用药及相应单一疗法对高血压患者家庭血压的影响：来自大型数据库的证据

Effects of the lercanidipine-enalapril combination vs. the corresponding monotherapies on home blood pressure in hypertension: evidence from a large database.

作者信息

Mancia Giuseppe, Omboni Stefano, Chazova Irina, Coca Antonio, Girerd Xavier, Haller Hermann, Parati Gianfranco, Pauletto Paolo, Pupek-Musialik Danuta, Svyshchenko Yevgeniya

机构信息

aUniversity of Milano-Bicocca and IRCCS, Istituto Auxologico Italiano, Milano bClinical Research Unit, Italian Institute of Telemedicine, Varese, Italy cDepartment of Systemic Hypertension, Institute of Clinical Cardiology, Moscow, Russia dHospital Clínic (IDIBAPS), University of Barcelona, Barcelona, Spain eCardiovascular Prevention Unit, Hôpital de la Pitié-Salpêtrière and Assistance Publique-Hôpitaux de Paris, Paris, France fDepartment of Nephrology and Hypertension, Hannover Medical School, Hannover, Germany gDepartment of Cardiology, IRCCS Ospedale San Luca, Istituto Auxologico Italiano and Department of Health Sciences, University of Milano Bicocca, Milano hDepartment of Internal Medicine, University Hospital of Treviso and University of Padova, Padova, Italy iDepartment of Biochemistry and Molecular Biology, Karol Marcinkowski University of Medical Sciences, Poznan, Poland.

出版信息

J Hypertens. 2016 Jan;34(1):139-48. doi: 10.1097/HJH.0000000000000767.

DOI:10.1097/HJH.0000000000000767

PMID:26630216

Abstract

OBJECTIVE

To compare a combination of a dihydropyridine calcium-channel blocker with an angiotensin converting enzyme inhibitor vs. monotherapy with one or the other drug and placebo for their effects on home blood pressure (HBP).

METHODS

After a 2-week placebo wash-out, patients with an elevated office blood pressure (BP) (diastolic 100-109 and systolic <180 mmHg) and HBP (diastolic ≥85 mmHg) were randomized double-blind to a 10-week treatment with placebo, lercanidipine, 10 or 20 mg daily, enalapril, 10 or 20 mg daily, or the four possible combinations. In addition to office BP, HBP was self-measured via a validated semiautomatic device twice in the morning and twice in the evening during the 7 days before randomization and at the end of treatment. Baseline and treatment HBP values were separately averaged for each day, morning, evening or the whole monitoring period, excluding the first day. Day-by-day HBP variability was defined as the SD or the variation coefficient of the daily BP averages.

RESULTS

Eight hundred and fifty-four patients with valid HBP recordings at baseline and at the end of treatment were analyzed (intention-to-treat population). From the baseline value (147.0±11.6 mmHg) systolic/diastolic HBP showed a small reduction (average baseline-adjusted change: -1.8/-1.6 mmHg) with placebo, a more marked significant fall with monotherapies (-8.8/-5.9 mmHg, P < 0.001/<0.001 vs. placebo) and even more with combination treatment (11.6/-7.6 mmHg, P < 0.001/ < 0.001 vs. placebo and P < 0.01/ < 0.05 vs. monotherapy). A similar pattern was observed for each of the days of the BP self-monitoring period as well as for either morning or evening values, although the difference between mono and combination treatment appeared to be consistently significant for the morning values only. Day-by-day systolic BP-SD was unaffected by placebo and slightly reduced by drug treatments, with no, however, significant changes in SBP-variation coefficient. Baseline and end of treatment HBP values showed a limited correlation with office BP values, this being particularly the case for treatment-induced changes (correlation coefficients: 0.37 for systolic and 0.45 for diastolic BP).

CONCLUSION

This large HBP database shows that the lercanidipine-enalapril combination lowers HBP more effectively than the corresponding monotherapies and placebo, and that this greater effect is consistent between days.

TRIAL REGISTRATION

ClinicalTrials.gov identifier: NCT01093807.

摘要

目的

比较二氢吡啶类钙通道阻滞剂与血管紧张素转换酶抑制剂联合用药、单药治疗及安慰剂对家庭血压（HBP）的影响。

方法

在为期2周的安慰剂洗脱期后，诊室血压（BP）升高（舒张压100 - 109mmHg且收缩压<180mmHg）且有家庭高血压（舒张压≥85mmHg）的患者被随机双盲分为接受安慰剂、乐卡地平（每日10或20mg）、依那普利（每日10或20mg）治疗10周，或四种可能的联合用药治疗。除诊室血压外，在随机分组前7天及治疗结束时，使用经过验证的半自动设备，让患者在早晨和晚上各自行测量家庭血压两次。将基线期和治疗期的家庭血压值按每天、早晨、晚上或整个监测期（不包括第一天）分别求平均值。每日家庭血压变异性定义为每日血压平均值的标准差或变异系数。

结果

对854例在基线期和治疗结束时均有有效家庭血压记录的患者（意向性治疗人群）进行了分析。收缩压/舒张压家庭血压从基线值（147.0±11.6mmHg）开始，安慰剂组有小幅下降（平均基线校正变化：-1.8/-1.6mmHg），单药治疗组下降更显著（-8.8/-5.9mmHg，与安慰剂相比P<0.001/<0.001），联合治疗组下降更多（11.6/-7.6mmHg，与安慰剂相比P<0.001/<0.001，与单药治疗相比P<0.01/<0.05）。在家庭血压自我监测期的每一天以及早晨或晚上的值中均观察到类似模式，不过单药治疗与联合治疗之间的差异仅在早晨值中始终具有显著性。每日收缩压标准差不受安慰剂影响，药物治疗使其略有降低，但收缩压变异系数无显著变化。基线期和治疗结束时的家庭血压值与诊室血压值的相关性有限，治疗引起的变化尤其如此（相关系数：收缩压为0.37，舒张压为0.45）。