Olmesartan for the Delay or Prevention of Microalbuminuria in Type 2 Diabetes
Olmesartan for the Delay or Prevention of Microalbuminuria in Type 2 Diabetes
复制标题
DOI：
10.1056/nejmoa1007994
复制
发表时间：
2011-03-10
影响因子：
158.5
通讯作者：
Viberti, Giancarlo
中科院分区：
文献类型：
--
作者：
Haller, Hermann;Ito, Sadayoshi;Viberti, Giancarlo
背景微量白蛋白尿是糖尿病肾病和早产儿心血管疾病的早期预测指标。我们调查了血管紧张素受体阻滞剂(ARB)治疗是否可以延缓或预防2型糖尿病患者微量白蛋白尿的发生。方法：在一项随机、双盲、多中心、对照试验中，我们将4447名2型糖尿病患者分为两组，分别接受奥美沙坦(每日40 mg)或安慰剂治疗，平均治疗时间为3.2年。根据需要使用额外的降压药(血管紧张素转换酶抑制剂或ARB除外)以将血压降至130/80毫米汞柱以下。主要结果是首次出现微量白蛋白尿的时间。结果服用奥美沙坦的患者和服用安慰剂的患者分别有近80%和71%的患者达到了目标血压(<；130/80 mm Hg)，临床测得的血压比安慰剂组低3.1/1.9 mm Hg。奥美沙坦组有8.2%的患者出现微量白蛋白尿(可评估的2160例患者中有178例)，安慰剂组为9.8%(2139例患者中有210例)；奥美沙坦组出现微量白蛋白尿的时间增加了23%(出现微量白蛋白尿的风险比为0.77；95%可信区间为0.63至0.94；P=0.01)。每组均有1%的患者血肌酐水平增加一倍。与安慰剂组相比，奥美沙坦组发生非致命性心血管事件的患者略少--2232名患者中有81名(3.6%)，2215名患者中有91名(4.1%)(P=0.37)，但发生致命心血管事件的人数更多--15名患者(0.7%)，3名患者(0.1%)(P=0.01)。这一差异部分归因于在既往存在的冠心病患者中，奥美沙坦组的心血管原因死亡率高于安慰剂组(564名患者中有11名患者为2.0%，540名患者中有1名为0.2%，P=0.02)。结论即使根据目前的标准，两组患者的血压控制都很好，但奥美沙坦组仍与微量白蛋白尿的延迟发生有关。在既往存在的冠心病患者中，服用奥美沙坦的致命性心血管事件的发生率较高，这一点令人担忧。
BACKGROUNDMicroalbuminuria is an early predictor of diabetic nephropathy and premature cardiovascular disease. We investigated whether treatment with an angiotensin-receptor blocker (ARB) would delay or prevent the occurrence of microalbuminuria in patients with type 2 diabetes and normoalbuminuria.METHODSIn a randomized, double-blind, multicenter, controlled trial, we assigned 4447 patients with type 2 diabetes to receive olmesartan ( at a dose of 40 mg once daily) or placebo for a median of 3.2 years. Additional antihypertensive drugs ( except angiotensin-converting-enzyme inhibitors or ARBs) were used as needed to lower blood pressure to less than 130/80 mm Hg. The primary outcome was the time to the first onset of microalbuminuria. The times to the onset of renal and cardiovascular events were analyzed as secondary end points.RESULTSThe target blood pressure (< 130/80 mm Hg) was achieved in nearly 80% of the patients taking olmesartan and 71% taking placebo; blood pressure measured in the clinic was lower by 3.1/1.9 mm Hg in the olmesartan group than in the placebo group. Microalbuminuria developed in 8.2% of the patients in the olmesartan group (178 of 2160 patients who could be evaluated) and 9.8% in the placebo group (210 of 2139); the time to the onset of microalbuminuria was increased by 23% with olmesartan (hazard ratio for onset of microalbuminuria, 0.77; 95% confidence interval, 0.63 to 0.94; P = 0.01). The serum creatinine level doubled in 1% of the patients in each group. Slightly fewer patients in the olmesartan group than in the placebo group had nonfatal cardiovascular events - 81 of 2232 patients (3.6%) as compared with 91 of 2215 patients (4.1%) (P = 0.37) - but a greater number had fatal cardiovascular events - 15 patients (0.7%) as compared with 3 patients (0.1%) (P = 0.01), a difference that was attributable in part to a higher rate of death from cardiovascular causes in the olmesartan group than in the placebo group among patients with preexisting coronary heart disease (11 of 564 patients [2.0%] vs. 1 of 540 [0.2%], P = 0.02).CONCLUSIONSOlmesartan was associated with a delayed onset of microalbuminuria, even though blood-pressure control in both groups was excellent according to current standards. The higher rate of fatal cardiovascular events with olmesartan among patients with preexisting coronary heart disease is of concern.