Fogari Roberto, Malamani GianDomenico, Zoppi Annalisa, Mugellini Amedeo, Rinaldi Andrea, Fogari Elena, Perrone Tiziano
Dipartimento di Medicina Interna, Clinica Medica, IRCCS Policlinico S. Matteo, Università di Pavia, Pavia, Italy.
Clin Ther. 2007 Mar;29(3):413-8. doi: 10.1016/s0149-2918(07)80079-8.
Use of the combination of an angiotensin-converting enzyme inhibitor (ACEI) and a calcium channel blocker (CCB) is considered a rational approach in patients whose hypertension is not controlled by monotherapy, providing better blood pressure (BP) control than the individual components with a lower incidence of adverse effects. In particular, such combinations have been found to reduce the incidence of ankle edema, the most common adverse effect of dihydropyridine annhypertensives.
The present study was undertaken to evaluate the effect on the development of ankle edema of adding the ACEI delapril to the CCB manidipine in patients with mild to moderate essential hypertension.
Patients between the ages of 30 and 70 years who had mild to moderate hypertension (diastolic BP [DBP] >90 and <110 mm Hg) were included in the study. After a 4-week placebo run-in period, eligible patients were randomized to receive 6 weeks each of manidipine 10 mg/d, delapril 30 mg/d, and both in a crossover fashion. There was a 2-week washout period between treatments. Ankle edema was assessed based on ankle-foot volume (AFV) and pretibial subcutaneous tissue pressure (PSTP). Sitting BP, AFV, and PSTP were measured at the end of the placebo run-in period and the end of each active-treatment period.
The study enrolled 40 patients with previously untreated hypertension (21 women, 19 men). Both manidipine and delapril monotherapy were associated with significant reductions from baseline in systolic BP (SBP) (mean [SD], -17.3 [4] and -14.8 [4] mm Hg, respectively; both, P<0.01) and DBP (-14.6 [3] and -12.9 [3] mm Hg; both, P<0.01). Compared with monotherapy, the combination of manidipine and delapril was associated with greater reductions from baseline in SBP (-21.8 [5] mm Hg; P<0.001) and DBP (-18.6 [4] mm Hg; P<0.001). Manidipme monotherapy was associated with significant increases from baseline in both AFV (7.9%; P<0.001) and PSTP (36.6%; P<0.01). Compared with manidipine alone, the combination of manidipine and delapril was associated with less pronounced increases in AFV (3.3%; P<0.05) and PSTP (10.4%; P<0.05). Ankle edema was clinically evident in 3 patients after receipt of manidipine monotherapy and in 1 patient after receipt of combination treatment.
In these patients with mild to moderate essential hypertension, the addition of delapril to manidipine partially counteracted the manidipine-induced microcirculatory changes responsible for ankle edema.
对于单药治疗无法控制高血压的患者，联合使用血管紧张素转换酶抑制剂（ACEI）和钙通道阻滞剂（CCB）被认为是一种合理的治疗方法，与单独使用其中一种药物相比，联合用药能更好地控制血压，且不良反应发生率更低。特别是，已发现此类联合用药可降低踝部水肿的发生率，踝部水肿是二氢吡啶类降压药最常见的不良反应。
本研究旨在评估在轻度至中度原发性高血压患者中，将ACEI地拉普利添加到CCB马尼地平中对踝部水肿发生情况的影响。
年龄在30至70岁之间、患有轻度至中度高血压（舒张压[DBP]＞90且＜110mmHg）的患者纳入本研究。经过4周的安慰剂导入期后，符合条件的患者被随机交叉接受6周的马尼地平10mg/d、地拉普利30mg/d以及两者联合治疗。治疗之间有2周的洗脱期。基于踝足容积（AFV）和胫前皮下组织压力（PSTP）评估踝部水肿。在安慰剂导入期结束时以及每个积极治疗期结束时测量坐位血压、AFV和PSTP。
本研究纳入了40例未经治疗的高血压患者（21例女性，19例男性）。马尼地平和地拉普利单药治疗均使收缩压（SBP）较基线显著降低（平均[标准差]分别为-17.3[4]和-14.8[4]mmHg；均P＜0.01）以及DBP降低（-14.6[3]和-12.9[3]mmHg；均P＜0.01）。与单药治疗相比，马尼地平和地拉普利联合治疗使SBP较基线降低更多（-21.8[5]mmHg；P＜0.001）以及DBP降低更多（-18.6[4]mmHg；P＜0.001）。马尼地平单药治疗使AFV（7.9%；P＜0.001）和PSTP（36.6%；P＜0.01）较基线均显著增加。与单独使用马尼地平相比，马尼地平和地拉普利联合治疗使AFV（3.3%；P＜0.05）和PSTP（10.4%；P＜0.05）增加的幅度较小。接受马尼地平单药治疗后有3例患者出现临床明显可见的踝部水肿，接受联合治疗后有1例患者出现。
在这些轻度至中度原发性高血压患者中，将地拉普利添加到马尼地平中可部分抵消马尼地平引起的导致踝部水肿的微循环变化。
