Rizzoni Damiano
a Internal Medicine, Department of Clinical and Experimental Sciences , University of Brescia , Brescia , Italy.
Curr Med Res Opin. 2016 Oct;32(sup2):17-23. doi: 10.1080/03007995.2016.1218836.
The dose-effect relationship of fixed-dose combinations of anti-hypertensive drugs has been only poorly explored. This pooled analysis investigates the dose-response relationship of fixed-dose lercanidipine + enalapril in patients with mild-to-moderate hypertension.
This was an individual patient data analysis of four randomized studies (n = 2340).
The primary efficacy variable was the change from baseline in sitting diastolic blood pressure (SDBP). Secondary variables were change from baseline in sitting systolic BP (SSBP), proportion of responder patients, and safety.
All fixed-dose combinations were superior to placebo in the reduction of SDBP. The greatest effect was observed with the market-available combination lercanidipine 20 mg/enalapril 20 mg (-15.3 mmHg vs. baseline; p < 0.05). The reduction in SDBP associated with the other two marketed fixed combinations of lercanidipine/enalapril were -10.7 mmHg for the 10 mg/20 mg combination and -9.8 mmHg for the 10 mg/10 mg combination (p < .05 for both comparisons). Similar findings were reported for SSBP reduction: the greatest effect was observed with lercanidipine 20 mg/enalapril 20 mg (-19.2 mmHg). The reduction in SSBP was -12.5 mmHg for the 10 mg/20 mg combination and -11.1 mmHg for the 10 mg/10 mg combination (p < .05 for all comparisons). The highest responder rate was reported with lercanidipine 20 mg/enalapril 20 mg (75.0%); this figure was 56.1% with the 10 mg/20 mg and 53.0% with the 10/10 mg combination. No safety concerns were reported.
This pooled analysis of four randomized studies shows evidence of a dose-response effect in BP reduction with different fixed combinations of lercanidipine + enalapril. To our knowledge, this is the first analysis investigating the dose-response effect of a specific fixed-dose combination of anti-hypertensive agents. Further studies on this intriguing topic are however necessary.
抗高血压药物固定剂量组合的剂量-效应关系尚未得到充分研究。本汇总分析旨在探讨轻度至中度高血压患者中固定剂量乐卡地平+依那普利的剂量-反应关系。
这是一项对四项随机研究（n = 2340）的个体患者数据分析。
主要疗效变量是静息舒张压（SDBP）相对于基线的变化。次要变量包括静息收缩压（SSBP）相对于基线的变化、反应者患者比例和安全性。
所有固定剂量组合在降低SDBP方面均优于安慰剂。市售的乐卡地平20mg/依那普利20mg组合效果最佳（相对于基线降低15.3mmHg；p < 0.05）。乐卡地平/依那普利的其他两种市售固定组合，10mg/20mg组合使SDBP降低10.7mmHg，10mg/10mg组合使SDBP降低9.8mmHg（两组比较p均< 0.05）。SSBP降低方面也有类似发现：乐卡地平20mg/依那普利20mg组合效果最佳（降低19.2mmHg）。10mg/20mg组合使SSBP降低12.5mmHg，10mg/10mg组合使SSBP降低11.1mmHg（所有比较p均< 0.05）。乐卡地平20mg/依那普利20mg组合的反应者率最高（75.0%）；10mg/20mg组合为56.1%，10/10mg组合为53.0%。未报告安全性问题。
对四项随机研究的这项汇总分析显示，不同固定组合的乐卡地平+依那普利在降低血压方面存在剂量-反应效应的证据。据我们所知，这是首次对特定抗高血压药物固定剂量组合的剂量-反应效应进行分析。然而，关于这个有趣主题还需要进一步研究。
