Boutitie Florent, Oprisiu Roxana, Achard Jean Michel, Mazouz Hakim, Wang Jiguang, Messerli Franz H, Gueyffier François, Fournier Albert
Hospices Civils de Lyon, Service de Biostatistique, Lyon, Université de Lyon I, Villeurbanne, CNRS, UMR 5558, Laboratoire Biostatistique Santé, Pierre-Benité, France.
J Hypertens. 2007 Aug;25(8):1543-53. doi: 10.1097/HJH.0b013e32814a5ae5.
Stroke prevention by antihypertensive therapy is believed to be related to the fall in blood pressure (BP). Experimental data have documented that activation of non-AT1 receptors of angiotensin II may exert anti-ischaemic mechanisms in the brain. The present meta-analysis of various randomized clinical trials attempts to relate stroke risk to angiotensin II formation during antihypertensive therapy.
Primary and secondary stroke prevention was examined in 26 prospective, randomized clinical trials including 206,632 patients without heart failure, in whom a total of 7,108 strokes occurred. The trials were selected because a difference in angiotensin II generation was expected between the two treatment arms on the basis of the drugs' pharmacodynamic effects, and allowed 36 evaluations of the relative risk of stroke.
In placebo-controlled trials, stroke risk was significantly higher with angiotensin II-decreasing than increasing drugs, but systolic BP decreased less in the former. Compared with an active therapy having a neutral effect on angiotensin II formation, stroke risk was also higher with angiotensin-decreasing drugs than with angiotensin-increasing drugs, whereas BP decrease was comparable with both drug classes. When angiotensin II-decreasing drugs were directly compared with angiotensin II-increasing drugs in the same trials, stroke risk was significantly increased. On-treatment systolic BP was minimally and significantly higher with angiotensin II-decreasing drugs, but not large enough to explain the excess in stroke risk.
Within the limitations of the methodology, our meta-analysis supports the hypothesis that angiotensin II-decreasing drugs are less stroke protective than angiotensin II-increasing drugs, although this difference is not entirely explained by their smaller BP-lowering effect.
抗高血压治疗预防卒中被认为与血压（BP）下降有关。实验数据表明，血管紧张素II的非AT1受体激活可能在大脑中发挥抗缺血机制。本项对各种随机临床试验的荟萃分析试图将卒中风险与抗高血压治疗期间的血管紧张素II形成相关联。
在26项前瞻性随机临床试验中对一级和二级卒中预防进行了研究，这些试验纳入了206,632例无心力衰竭的患者，其中共发生7108例卒中。选择这些试验是因为基于药物的药效学效应，预计两个治疗组之间血管紧张素II生成存在差异，并允许对卒中的相对风险进行36次评估。
在安慰剂对照试验中，降低血管紧张素II的药物组卒中风险显著高于升高血管紧张素II的药物组，但前者收缩压下降幅度较小。与对血管紧张素II形成具有中性作用的活性治疗相比，降低血管紧张素的药物组卒中风险也高于升高血管紧张素的药物组，而两组药物的血压下降幅度相当。在同一试验中直接比较降低血管紧张素II的药物与升高血管紧张素II的药物时，卒中风险显著增加。使用降低血管紧张素II的药物时，治疗期间的收缩压最低且显著更高，但升高幅度不足以解释卒中风险的增加。
在方法学的局限性范围内，我们的荟萃分析支持以下假设：降低血管紧张素II的药物在预防卒中方面不如升高血管紧张素II的药物有效，尽管这种差异不能完全由其较小的降压作用来解释。
