Staessen J A, Fagard R, Thijs L, Celis H, Birkenhäger W H, Bulpitt C J, de Leeuw P W, Fletcher A E, Babarskiene M R, Forette F, Kocemba J, Laks T, Leonetti G, Nachev C, Petrie J C, Tuomilehto J, Vanhanen H, Webster J, Yodfat Y, Zanchetti A
Department of Cardiovascular and Molecular Research, University of Leuven, Belgium.
Arch Intern Med. 1998;158(15):1681-91. doi: 10.1001/archinte.158.15.1681.
In 1989, the European Working Party on High Blood Pressure in the Elderly started the double-blind, placebo-controlled, Systolic Hypertension in Europe Trial to test the hypothesis that antihypertensive drug treatment would reduce the incidence of fatal and nonfatal stroke in older patients with isolated systolic hypertension. This report addresses whether the benefit of antihypertensive treatment varied according to sex, previous cardiovascular complications, age, initial blood pressure (BP), and smoking or drinking habits in an intention-to-treat analysis and explores whether the morbidity and mortality results were consistent in a per-protocol analysis.
After stratification for center, sex, and cardiovascular complications, 4695 patients 60 years of age or older with a systolic BP of 160 to 219 mm Hg and diastolic BP less than 95 mm Hg were randomized. Active treatment consisted of nitrendipine (10-40 mg/d), with the possible addition of enalapril maleate (5-20 mg/d) and/or hydrochlorothiazide (12.5-25 mg/d), titrated or combined to reduce the sitting systolic BP by at least 20 mm Hg, to below 150 mm Hg. In the control group, matching placebo tablets were employed similarly.
In the intention-to-treat analysis, male sex, previous cardiovascular complications, older age, higher systolic BP, and smoking at randomization were positively and independently correlated with cardiovascular risk. Furthermore, for total (P = .009) and cardiovascular (P = .09) mortality, the benefit of antihypertensive drug treatment weakened with advancing age; for total mortality (P = .05), the benefit increased with higher systolic BP at entry, while for fatal and nonfatal stroke (P = .01), it was most evident in nonsmokers (92.5% of all patients). In the perprotocol analysis, active treatment reduced total mortality by 24% (P = .05), reduced all fatal and nonfatal cardiovascular end points by 32% (P<.001), reduced all strokes by 44% (P = .004), reduced nonfatal strokes by 48% (P = .005), and reduced all cardiac end points, including sudden death, by 26% (P = .05).
In elderly patients with isolated systolic hypertension, stepwise antihypertensive drug treatment, starting with the dihydropyridine calcium channel blocker nitrendipine, improves prognosis. The per-protocol analysis suggested that treating 1000 patients for 5 years would prevent 24 deaths, 54 major cardiovascular end points, 29 strokes, or 25 cardiac end points. The effects of antihypertensive drug treatment on total and cardiovascular mortality may be attenuated in very old patients.
1989年，欧洲老年高血压工作组启动了一项双盲、安慰剂对照的欧洲收缩期高血压试验，以检验抗高血压药物治疗能否降低单纯收缩期高血压老年患者致命和非致命性卒中发生率这一假设。本报告探讨在意向性分析中，抗高血压治疗的益处是否因性别、既往心血管并发症、年龄、初始血压（BP）、吸烟或饮酒习惯而异，并在符合方案分析中探讨发病率和死亡率结果是否一致。
按中心、性别和心血管并发症分层后，将4695例60岁及以上、收缩压为160至219 mmHg且舒张压低于95 mmHg的患者随机分组。积极治疗包括硝苯地平（10 - 40 mg/d），可能加用马来酸依那普利（5 - 20 mg/d）和/或氢氯噻嗪（12.5 - 25 mg/d），通过滴定或联合用药使坐位收缩压至少降低20 mmHg，降至150 mmHg以下。对照组同样使用匹配的安慰剂片。
在意向性分析中，男性、既往心血管并发症、年龄较大、收缩压较高以及随机分组时吸烟与心血管风险呈正相关且相互独立。此外，对于总死亡率（P = .009）和心血管死亡率（P = .09），抗高血压药物治疗的益处随年龄增长而减弱；对于总死亡率（P = .05），治疗益处随入组时收缩压升高而增加，而对于致命和非致命性卒中（P = .01），在不吸烟者中最为明显（占所有患者的92.5%）。在符合方案分析中，积极治疗使总死亡率降低24%（P = .05），使所有致命和非致命性心血管终点降低32%（P<.001），使所有卒中降低44%（P = .004），使非致命性卒中降低48%（P = .005），使所有心脏终点（包括猝死）降低26%（P = .05）。
在单纯收缩期高血压老年患者中，从二氢吡啶类钙通道阻滞剂硝苯地平开始的逐步抗高血压药物治疗可改善预后。符合方案分析表明，治疗1000例患者5年可预防24例死亡、54个主要心血管终点、29例卒中或25个心脏终点。抗高血压药物治疗对总死亡率和心血管死亡率的影响在高龄患者中可能会减弱。
