国际硝苯地平控释片研究（INSIGHT）：长效钙通道阻滞剂或利尿剂双盲治疗患者的发病率和死亡率——高血压治疗以干预为目标

Morbidity and mortality in patients randomised to double-blind treatment with a long-acting calcium-channel blocker or diuretic in the International Nifedipine GITS study: Intervention as a Goal in Hypertension Treatment (INSIGHT).

作者信息

Brown M J, Palmer C R, Castaigne A, de Leeuw P W, Mancia G, Rosenthal T, Ruilope L M

机构信息

Clinical Pharmacology Unit, University of Cambridge, UK.

出版信息

Lancet. 2000 Jul 29;356(9227):366-72. doi: 10.1016/S0140-6736(00)02527-7.

DOI:10.1016/S0140-6736(00)02527-7

PMID:10972368

Abstract

BACKGROUND

The efficacy of antihypertensive drugs newer than diuretics and beta-blockers has not been established. We compared the effects of the calcium-channel blocker nifedipine once daily with the diuretic combination co-amilozide on cardiovascular mortality and morbidity in high-risk patients with hypertension.

METHODS

We did a prospective, randomised, double-blind trial in Europe and Israel in 6321 patients aged 55-80 years with hypertension (blood pressure > or = 150/95 mm Hg, or > or = 160 mm Hg systolic). Patients had at least one additional cardiovascular risk factor. We randomly assigned patients nifedipine 30 mg in a long-acting gastrointestinal-transport-system (GITS) formulation (n=3157), or co-amilozide (hydrochlorothiazide 25 mg [corrected] plus amiloride 2.5 mg; n=3164). Dose titration was by dose doubling, and addition of atenolol 25-50 mg or enalapril 5-10 mg. The primary outcome was cardiovascular death, myocardial infarction, heart failure, or stroke. Analysis was done by intention to treat.

FINDINGS

Primary outcomes occurred in 200 (6.3%) patients in the nifedipine group and in 182 (5.8%) in the co-amilozide group (18.2 vs 16.5 events per 1000 patient-years; relative risk 1.10 [95% CI 0.91-1.34], p=0.35). Overall mean blood pressure fell from 173/99 mm Hg (SD 14/8) to 138/82 mm Hg (12/7). There was an 8% excess of withdrawals from the nifedipine group because of peripheral oedema (725 vs 518, p<0.0001), but serious adverse events were more frequent in the co-amilozide group (880 vs 796, p=0.02). Deaths were mainly non-vascular (nifedipine 176 vs co-amilozide 172; p=0.81). 80% of the primary events occurred in patients receiving randomised treatment (157 nifedipine, 147 co-amilozide, difference 0.33% [-0.7 to 1.4]).

INTERPRETATION

Nifedipine once daily and co-amilozide were equally effective in preventing overall cardiovascular or cerebrovascular complications. The choice of drug can be decided by tolerability and blood-pressure response rather than long-term safety or efficacy.

摘要

背景

比利尿剂和β受体阻滞剂更新的抗高血压药物的疗效尚未得到证实。我们比较了每日一次服用钙通道阻滞剂硝苯地平与利尿剂复方阿米洛利对高危高血压患者心血管死亡率和发病率的影响。

方法

我们在欧洲和以色列对6321例年龄在55 - 80岁的高血压患者（血压≥150/95 mmHg，或收缩压≥160 mmHg）进行了一项前瞻性、随机、双盲试验。患者至少有一项其他心血管危险因素。我们将患者随机分为服用长效胃肠道转运系统（GITS）制剂的硝苯地平30 mg组（n = 3157）或复方阿米洛利组（氢氯噻嗪25 mg [校正后]加阿米洛利2.5 mg；n = 3164）。通过剂量加倍以及加用25 - 50 mg阿替洛尔或5 - 10 mg依那普利进行剂量滴定。主要结局为心血管死亡、心肌梗死、心力衰竭或中风。采用意向性分析。

结果

硝苯地平组200例（6.3%）患者发生主要结局，复方阿米洛利组182例（5.8%）患者发生主要结局（每1000患者年18.2例 vs 16.5例事件；相对风险1.10 [95%CI 0.91 - 1.34]，p = 0.35）。总体平均血压从173/99 mmHg（标准差14/8）降至138/82 mmHg（12/7）。硝苯地平组因外周水肿退出研究的比例高出8%（725例 vs 518例，p<0.0001），但复方阿米洛利组严重不良事件更频繁（880例 vs 796例，p = 0.02）。死亡主要为非血管性（硝苯地平组176例 vs 复方阿米洛利组172例；p = 0.81）。80%的主要事件发生在接受随机治疗的患者中（硝苯地平组157例，复方阿米洛利组147例，差异0.33% [-0.7至1.4]）。