Bots M L, Remme W J, Lüscher T F, Fox K M, Bertrand M, Ferrari R, Simoons M L, Grobbee D E
Julius Center for Health Sciences and Primary Care, HP Str 6.131, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands.
Cardiovasc Drugs Ther. 2007 Aug;21(4):269-79. doi: 10.1007/s10557-007-6041-3.
ACE inhibition results in secondary prevention of coronary artery disease (CAD) through different mechanisms including improvement of endothelial dysfunction. The Perindopril-Function of the Endothelium in Coronary artery disease Trial (PERFECT) evaluated whether long-term administration of perindopril improves endothelial dysfunction.
PERFECT is a 3-year double blind randomised placebo controlled trial to determine the effect of perindopril 8 mg once daily on brachial artery endothelial function in patients with stable CAD without clinical heart failure. Endothelial function in response to ischaemia was assessed using ultrasound. Primary endpoint was difference in flow-mediated vasodilatation (FMD) assessed at 36 months.
In 20 centers, 333 patients randomly received perindopril or matching placebo. Ischemia-induced FMD was 2.7% (SD 2.6). In the perindopril group FMD went from 2.6% at baseline to 3.3% at 36 months and in the placebo group from 2.8 to 3.0%. Change in FMD after 36 month treatment was 0.55% (95% confidence interval -0.36, 1.47; p = 0.23) higher in perindopril than in placebo group. The rate of change in FMD per 6 months was 0.14% (SE 0.05, p = 0.02) in perindopril and 0.02% (SE 0.05, p = 0.74) in placebo group (0.12% difference in rate of change p = 0.07).
Perindopril resulted in a modest, albeit not statistically significant, improvement in FMD.
血管紧张素转换酶(ACE)抑制作用通过不同机制实现对冠状动脉疾病(CAD)的二级预防,包括改善内皮功能障碍。培哚普利在冠状动脉疾病中对内皮功能的影响试验(PERFECT)评估了长期服用培哚普利是否能改善内皮功能障碍。
PERFECT是一项为期3年的双盲随机安慰剂对照试验,旨在确定每日一次服用8mg培哚普利对无临床心力衰竭的稳定型CAD患者肱动脉内皮功能的影响。使用超声评估缺血状态下的内皮功能。主要终点是36个月时评估的血流介导的血管舒张(FMD)差异。
在20个中心,333例患者随机接受培哚普利或匹配的安慰剂。缺血诱导的FMD为2.7%(标准差2.6)。在培哚普利组,FMD从基线时的2.6%升至36个月时的3.3%,而在安慰剂组从2.8%升至3.0%。36个月治疗后培哚普利组FMD的变化比安慰剂组高0.55%(95%置信区间-0.36,1.47;p = 0.23)。培哚普利组每6个月FMD的变化率为0.14%(标准误0.05,p = 0.02),安慰剂组为0.02%(标准误0.05,p = 0.74)(变化率差异0.12%,p = 0.07)。
培哚普利使FMD有适度改善,尽管无统计学意义。