Cremonesi Giovanni, Cavalieri Luca, Bacchelli Stefano, Esposti Daniela Degli, Cikes Ivo, Dobovisek Jurij, Zeman Jan, Borghi Claudio, Ambrosioni Ettore
Chiesi Farmaceutici SpA, Parma, Italy.
Department of Internal Medicine"D. Campanacci," University of Bologna, Bologna, Italy.
Curr Ther Res Clin Exp. 2003 May;64(5):290-300. doi: 10.1016/S0011-393X(03)00084-5.
Several studies have shown that antihypertensive monotherapy is commonly insufficient to control blood pressure (BP) in hypertensive patients and that concomitant use of ≥2 drugs is necessary in ∼50% of these patients. The combination of an angiotensin-converting enzyme (ACE) inhibitor and a diuretic, delapril plus indapamide (D + I), has been shown to be effective and tolerable, with no interaction between the 2 components. Another widely used combination of ACE inhibitor and diuretic is lisinopril plus hydrochlorothiazide (L + H).
The aims of this study were to confirm the antihypertensive efficacy and tolerability of the fixed combination of D + I in mild to moderate hypertension, and to compare its therapeutic efficacy and tolerability with that of L + H.
The antihypertensive efficacy and tolerability of a fixed combination of D + I (30-mg + 2.5-mg tablets once daily) or L + H (20-mg + 12.5-mg tablets once daily) in patients with mild to moderate hypertension were compared in a multinational, multicenter, randomized, 2-armed, parallel-group study. Eligible patients were aged 18 to 75 years and had a diastolic blood pressure (DBP) 95 to 115 mm Hg and a systolic blood pressure (SBP) ≤180 mm Hg, both measured in the sitting position. After a single-blind, placebo run-in period of 2 weeks, patients were randomized to receive 1 of the 2 treatments for a 12-week period. The primary efficacy end point was the BP normalization rate (ie, the percentage of patients with a sitting DBP ≤90 mm Hg) after 12 weeks of treatment. Secondary end points were as follows: (1) the responder rate (ie, the percentage of patients whose sitting DBP was reduced by ≥10 mm Hg from baseline or had a DBP ≤90 mm Hg after 12 weeks of treatment), (2) the percentage of patients with a DBP ≤85 mm Hg, and (3) changes in sitting SBP and DBP after 4, 8, and 12 weeks of treatment.
A total of 159 hypertensive patients (88 women, 71 men) were randomized to receive D + I (44 women, 36 men; mean [SD] age, 53 [(11)] years) or L + H (44 women, 35 men; mean [SD] age, 55 [(10)] years). No significant between-group differences were found in any of the primary or secondary end points of the study. Both combinations induced a significant reduction in sitting DBP and SBP from baseline (P<0.001 for both groups at week 12), without significant differences between the groups. Five mild to moderate adverse drug reactions (ADRs) occurred in each treatment group. No patient dropped out of the study because of an ADR.
This study showed no difference between D + I and L + H interms of antihypertensive efficacy or tolerability in patients with mild to moderate hypertension.
多项研究表明，抗高血压单药治疗通常不足以控制高血压患者的血压（BP），约50%的此类患者需要联合使用≥2种药物。血管紧张素转换酶（ACE）抑制剂与利尿剂联合使用，即地拉普利加吲达帕胺（D + I），已被证明是有效且耐受性良好的，两种成分之间无相互作用。另一种广泛使用的ACE抑制剂与利尿剂的组合是赖诺普利加氢氯噻嗪（L + H）。
本研究的目的是确认D + I固定复方在轻至中度高血压中的降压疗效和耐受性，并将其治疗效果和耐受性与L + H进行比较。
在一项多国、多中心、随机、双组、平行组研究中，比较了D + I（30毫克 + 2.5毫克片剂，每日一次）或L + H（20毫克 + 12.5毫克片剂，每日一次）固定复方在轻至中度高血压患者中的降压疗效和耐受性。符合条件的患者年龄在18至75岁之间，坐位舒张压（DBP）为95至115毫米汞柱，收缩压（SBP）≤180毫米汞柱。经过2周的单盲、安慰剂导入期后，患者被随机分配接受2种治疗中的1种，为期12周。主要疗效终点是治疗12周后的血压正常化率（即坐位DBP≤90毫米汞柱的患者百分比）。次要终点如下：（1）反应率（即坐位DBP较基线降低≥10毫米汞柱或治疗12周后DBP≤90毫米汞柱的患者百分比），（2）DBP≤85毫米汞柱的患者百分比，以及（3）治疗4、8和12周后坐位SBP和DBP的变化。
共有159例高血压患者（88例女性，71例男性）被随机分配接受D + I（44例女性，36例男性；平均[标准差]年龄，53 [（11）]岁）或L + H（44例女性，35例男性；平均[标准差]年龄，55 [（10）]岁）。在该研究的任何主要或次要终点中，均未发现组间有显著差异。两种组合均使坐位DBP和SBP较基线显著降低（第12周时两组均P<0.001），组间无显著差异。每个治疗组均发生了5例轻至中度药物不良反应（ADR）。没有患者因ADR退出研究。
本研究表明，在轻至中度高血压患者中，D + I和L + H在降压疗效或耐受性方面无差异。
