Vaur L, Bobrie G, Dutrey-Dupagne C, Dubroca I, Vaisse B, d'Yvoire M B, Elkik F, Chatellier G, Menard J
Laboratoires Roussel, Direction Médicale, Paris, France.
Am J Hypertens. 1998 Feb;11(2):165-73. doi: 10.1016/s0895-7061(97)00420-2.
The aim of this study was to compare blood pressure rise after interruption of two angiotensin converting enzyme (ACE) inhibitors in hypertensive patients. After a 2-week placebo run-in period, hypertensive patients were treated with either trandolapril 2 mg once daily or perindopril 4 mg once daily for 4 weeks in a double-blind design. A placebo was then administered for 1 week. Three periods of 1-week home self-measured blood pressure (SMBP) were programmed: end of placebo run-in period, end of treatment period, and final withdrawal placebo period. Every day, three consecutive measurements were requested both in the evening and in the morning. Individual reversion to baseline BP level was studied in the subgroup of patients responding to therapy (evening diastolic SMBP decrease > or =6 mm Hg). The ratio (R) of mean post-drug DBP lowering (residual effect) over evening on-drug DBP lowering (full effect) was used to study reversion to baseline. Patients exhibiting a lower value than the median of this ratio were called Reverters, whereas others were called Nonreverters. One hundred-nineteen patients entered the analysis. During the treatment period, mean SMBP decreased significantly, from 150 +/- 14/97 +/- 7 mm Hg to 139 +/- 15/91 +/- 9 mm Hg (all P < .001). The on-drug BP level was similar in the evening in the two treatment groups. However, both systolic and diastolic morning SMBP levels were significantly lower in the trandolapril group. After drug discontinuation, the mean BP level significantly rose to 144 +/- 14/94 +/- 9 mm Hg (all P = .01) but remained lower than the baseline BP values (P = .003 for SBP and P = .002 for DBP). The post-drug BP level was significantly lower in the trandolapril group than in the perindopril group. Seventy-four patients were responders to therapy. In this subgroup, the median of the R ratio used to analyze reversion to baseline after drug discontinuation was 44%. Nonreverters were characterized by a sustained on-drug BP decrease, compared to Reverters. We therefore conclude that ACE inhibitor treatment withdrawal is accompanied by a rapid rise in BP (within 48 h), followed by a 5-day BP plateau that is lower than the initial level. Reverters to baseline after drug discontinuation were more likely to be insufficiently controlled during therapy, particularly in the morning. The longer duration of action of trandolapril was associated with a lower BP level during both the morning during the active treatment phase and the 1-week posttreatment phase.
本研究的目的是比较高血压患者中断两种血管紧张素转换酶(ACE)抑制剂治疗后血压的升高情况。在为期2周的安慰剂导入期后,高血压患者采用双盲设计,接受每日一次2 mg群多普利或每日一次4 mg培哚普利治疗4周。随后给予安慰剂治疗1周。安排了三个为期1周的家庭自测血压(SMBP)阶段:安慰剂导入期末、治疗期末和最终撤药安慰剂期。每天要求在早晨和晚上连续测量三次。在对治疗有反应的患者亚组(晚上舒张压SMBP下降≥6 mmHg)中研究个体血压恢复到基线水平的情况。用药物后舒张压降低均值(残余效应)与晚上用药时舒张压降低均值(完全效应)的比值(R)来研究血压恢复到基线的情况。该比值低于中位数的患者被称为恢复者,其他患者被称为非恢复者。119例患者进入分析。在治疗期间,平均SMBP显著下降,从150±14/97±7 mmHg降至139±15/91±9 mmHg(所有P<0.001)。两个治疗组晚上的用药时血压水平相似。然而,群多普利组早晨的收缩压和舒张压SMBP水平均显著更低。停药后,平均血压水平显著升至144±14/94±9 mmHg(所有P = 0.01),但仍低于基线血压值(收缩压P = 0.003,舒张压P = 0.002)。群多普利组停药后的血压水平显著低于培哚普利组。74例患者对治疗有反应。在该亚组中,用于分析停药后血压恢复到基线情况的R比值中位数为44%。与恢复者相比,非恢复者的特点是用药时血压持续下降。因此,我们得出结论,停用ACE抑制剂治疗后血压迅速升高(48小时内),随后出现一个比初始水平低的5天血压平台期。停药后恢复到基线的患者在治疗期间尤其是早晨更可能控制不佳。群多普利作用时间较长与积极治疗阶段早晨以及治疗后1周的较低血压水平相关。