Marre Michel, Lievre Michel, Chatellier Gilles, Mann Johannes F E, Passa Philippe, Ménard Joël
Endocrinologie-Diabétologie-Nutrition, Groupe Hospitalier Bichat-Claude Bernard, Assistance Publique des Hôpitaux de Paris, 46 rue Henri Huchard, 75877 Paris Cedex 18, France.
BMJ. 2004 Feb 28;328(7438):495. doi: 10.1136/bmj.37970.629537.0D. Epub 2004 Feb 11.
To investigate whether a low dose of the angiotensin converting enzyme (ACE) inhibitor ramipril lowers cardiovascular and renal events in patients with type 2 diabetes who have microalbuminuria or proteinuria.
Randomised, double blind, parallel group trial comparing ramipril (1.25 mg/day) with placebo (on top of usual treatment) for cardiovascular and renal outcomes for at least three years.
Multicentre, primary care study conducted mostly by general practitioners in 16 European and north African countries.
4912 patients with type 2 diabetes aged >50 years who use oral antidiabetic drugs and have persistent microalbuminuria or proteinuria (urinary albumin excretion > or = 20 mg/l in two consecutive samples), and serum creatinine < or = 150 micromol/l.
The primary outcome measure was the combined incidence of cardiovascular death, non-fatal myocardial infarction, stroke, heart failure leading to hospital admission, and end stage renal failure.
Participants were followed for 3 to 6 (median 4) years. There were 362 primary events among the 2443 participants taking ramipril (37.8 per 1000 patient years) and 377 events among the 2469 participants taking placebo (38.8 per 1000 patient years; hazard ratio 1.03 (95% confidence interval 0.89 to 1.20, P = 0.65)). None of the components of the primary outcome was reduced. Ramipril lowered systolic and diastolic blood pressures (by 2.43 and 1.06 mm Hg respectively after two years) and favoured regression from microalbuminuria (20-200 mg/l) or proteinuria (> 200mg/l) to normal level (< 20 mg/l) or microalbuminuria (P < 0.07) in 1868 participants who completed the study.
Low dose (1.25 mg) ramipril once daily has no effect on cardiovascular and renal outcomes of patients with type 2 diabetes and albuminuria, despite a slight decrease in blood pressure and urinary albumin. The cardiovascular benefits of a daily higher dose (10 mg) ramipril observed elsewhere are not found with an eightfold lower daily dose.
研究低剂量血管紧张素转换酶（ACE）抑制剂雷米普利是否能降低患有微量白蛋白尿或蛋白尿的2型糖尿病患者发生心血管和肾脏事件的风险。
随机、双盲、平行组试验，比较雷米普利（1.25毫克/天）与安慰剂（在常规治疗基础上）对心血管和肾脏结局的影响，为期至少三年。
多中心初级保健研究，主要由16个欧洲和北非国家的全科医生开展。
4912例年龄大于50岁的2型糖尿病患者，他们使用口服降糖药，且有持续性微量白蛋白尿或蛋白尿（连续两次样本尿白蛋白排泄量≥20毫克/升），血清肌酐≤150微摩尔/升。
主要结局指标是心血管死亡、非致死性心肌梗死、中风、导致住院的心力衰竭以及终末期肾衰竭的合并发生率。
参与者随访了3至6年（中位时间4年）。服用雷米普利的2443名参与者中有362例发生主要事件（每1000患者年37.8例），服用安慰剂的2469名参与者中有377例发生主要事件（每1000患者年38.8例；风险比1.03（95%置信区间0.89至1.20，P = 0.65））。主要结局的各个组成部分均未降低。雷米普利降低了收缩压和舒张压（两年后分别降低2.43和1.06毫米汞柱），并且在完成研究的1868名参与者中，有利于微量白蛋白尿（20 - 200毫克/升）或蛋白尿（>200毫克/升）回归至正常水平（<20毫克/升）或微量白蛋白尿（P < 0.07）。
尽管血压和尿白蛋白略有下降，但每日一次低剂量（1.25毫克）雷米普利对2型糖尿病和白蛋白尿患者的心血管和肾脏结局无影响。在其他地方观察到的每日高剂量（10毫克）雷米普利的心血管益处，在每日剂量降低八倍的情况下未发现。
