降压治疗对中国脑血管病患者脑卒中再发预防的多中心随机双盲对照临床研究

Effects of blood pressure lowering treatment on stroke recurrence in patients with cerebrovascular diseases-a large-scale, randomized, placebo controlled trial

目的评估降压治疗对脑血管病患者脑卒中再发的影响。方法入选近5年内有脑卒中或短暂性脑缺血发作病史的患者,且无研究药物适应证或禁忌证,无血压入选标准。研究为大样本、随机、双盲、安慰剂对照临床试验。导入期4周后,1520例患者被随机分为培哚普利(或加吲哒帕胺)治疗组或安慰剂对照组,随访治疗4年。主要终点是脑卒中事件,次要终点包括心血管死亡,心肌梗死,全因死亡等。结果762例被分为治疗组,758例为对照组。治疗组与对照组两组患者基础临床特征相似。治疗组与对照组的男性分别为70·8%和70·5%;脑卒中史占93·8%和93·4%;基础血压为(145·3±20·2)/(86·8±11·1)mmHg(1mmHg=0·133kPa)和(145·3±20·3)/(87·2±10·8)mmHg;平均年龄为(63·9±7·5)岁和(63·8±7·7)岁。随访4年,治疗组较对照组血压平均下降14/6mmHg,治疗组脑卒中再发率(8·8%)较对照组(19·4%)明显减少,相对危险下降55%(P<0·001);心肌梗死发生(1·4%比2·8%)危险下降48%(P=0·070);心血管死亡(3·6%比6·6%)危险减少45%(P=0·010);总死亡(6·3%比9·8%)危险减少36%(P=0·010)。降压治疗对男性或女性、中年或老年、有或无高血压史、脑梗死史或脑出血史患者均有益。结论降压治疗对脑血管病患者的脑卒中再发的预防是有益的。

Objectives To investigate the effects of blood pressure lowering treatment on stroke recurrence among Chinese patients with previous cerebrovascular diseases. Methods Patients were eligible if they had a history of stroke or transient ischaemic attack （TIA） within the previous 5 years. Participants had no definite indication or contraindication for study drugs. There were no blood pressure entry criteria. This study was a large-scale randomised, double-blind, placebo controlled clinical trial. After 4 weeks runin period, 1520 randomised patients received either ACE inhibitor-perindopril （ ＋ diuretic-indapamide） treatment or matching placebo for 4 years. The primary study outcome was stroke event. Secondary outcomes included cardiovascular death, myocardial infarction, all-cause death and blood pressure. Results Ssven hundred and sixty-two were assigned active treatment and 758 assigned placebo. The characteristics of randomised patients of active and control groups were similar. In active and control groups： 70. 8% and 70.5% were male, 93. 8% and 93.4% had a history of stroke （haemorrhagic or cerebral infarction）. Baseline mean blood pressure in the active and control groups were 145. 3 ± 20. 2/86. 8 ± 11.1 mm Hg and 145. 3 ± 20. 3/87. 2 ± 10. 8 mm Hg, and mean age were 63.9 ± 7. 5 and 63.8 ± 7. 7 years, respectively. Blood pressure in those assigned active treatment was reduced on average 14/6 mm Hg more than placebo at 4 years. During double-blind treatment, active treatment reduced stroke recurrence （8. 8% vs 19. 4% ） by 55% （P 〈0.001）, myocardial infarction （1.4% vs 2. 8%） by 48% （P = 0.070）, cardiovascular mortality （3.6% vs 6. 6. % ） by 45% （P = 0. 010）, and all-cause mortality （6. 3% vs 9. 8% ） by 36% （P = 0. 010）. These benefits were achieved similarly in all subgroups： male or female, middle-aged or elderly, with or without hypertensive, cerebral infarct or haemorrhagic stroke. Conclusion 4 years of blood pressure lowering treatment was beneficial in Chinese patients with previous cerebrovascular diseases.