Does a change in angiotensin II formation caused by antihypertensive drugs affect the risk of stroke? A meta-analysis of trials according to treatment with potentially different effects on angiotensin II

被引:35
作者
Boutitie, Florent
Oprisiu, Roxana
Achard, Jean Michel
Mazouz, Hakim
Wang, Jiguang
Messerli, Franz H.
Gueyffier, Francois
Fournier, Albert [1 ]
机构
[1] CHU Amiens, Dept Nephrol, Amiens, France
[2] CHU Amiens, Dept Geriatr, Amiens, France
[3] CNRS, UMR 5558, Lab Biostat Sante, Pierre Benite, France
[4] Univ Lyon 1, Hospices Civils Lyon, Serv Biostat, F-69622 Villeurbanne, France
[5] CHU Limoges, Dept Physiol, Limoges, France
[6] INSERM, CIC2201, F-69008 Lyon, France
[7] Shanghai Jiao Tong Univ, Sch Med, Ruijin Hosp, Ctr Epidemiol Studies & Clin Trials, Shanghai 200030, Peoples R China
[8] St Lukes Roosevelt Hosp, Dept Cardiol, New York, NY USA
关键词
anti hypertensive drugs; meta-analysis; meta-regression; non-angiotensin II type 1 receptors of angiotensin; stroke prevention; risk reduction beyond blood pressure;
D O I
10.1097/HJH.0b013e32814a5ae5
中图分类号
R6 [外科学];
学科分类号
1002 ; 100210 ;
摘要
Background Stroke prevention by anti hypertensive therapy is believed to be related to the fall in blood pressure (BP). Experimental data have documented that activation of non-AT, 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 anti hypertensive therapy. Methods 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 7108 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. Findings 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-clecreasing 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. Conclusion 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.
引用
收藏
页码:1543 / 1553
页数:11
相关论文
共 86 条
[1]   Protection against ischemia: a physiological function of the renin-angiotensin system [J].
Achard, JM ;
Fournier, A ;
Mazouz, H ;
Caride, VJ ;
Penar, PL ;
Fernandez, LA .
BIOCHEMICAL PHARMACOLOGY, 2001, 62 (03) :261-271
[2]  
*ALLHAT OFF COORD, 2002, JAMA-J AM MED ASSOC, V288, P2981, DOI DOI 10.1001/JAMA.288.23.2981
[3]  
AMERY A, 1985, LANCET, V1, P1349
[4]  
[Anonymous], 1991, JAMA, V265, P3255
[5]   EFFECTS OF TREATMENT ON MORBIDITY IN HYPERTENSION - RESULTS IN PATIENTS WITH DIASTOLIC BLOOD PRESSURES AVERAGING 115 THROUGH 129 MM HG [J].
不详 .
JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 1967, 202 (11) :1028-&
[6]  
[Anonymous], 1993, Stroke, V24, P543
[7]  
[Anonymous], 1970, JAMA-J AM MED ASSOC, V213, P1143, DOI DOI 10.1001/JAMA.213.7.1143
[8]  
[Anonymous], 1979, JAMA
[9]   Effects of chronic calcium channel blockade on sympathetic nerve activity in hypertension [J].
Binggeli, C ;
Corti, R ;
Sudano, I ;
Luscher, TF ;
Noll, G .
HYPERTENSION, 2002, 39 (04) :892-896
[10]   Principal results of the Controlled Onset Verapamil Investigation of Cardiovascular End Points (CONVINCE) Trial [J].
Black, HR ;
Elliott, WJ ;
Grandits, G ;
Grambsch, P ;
Lucente, T ;
White, WB ;
Neaton, JD ;
Grimm, RH ;
Hansson, L ;
Lacourcière, Y ;
Muller, J ;
Sleight, P ;
Weber, MA ;
Williams, G ;
Wittes, J ;
Zanchetti, A ;
Anders, RJ .
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 2003, 289 (16) :2073-2082