National Institute for Health Research, School for Primary Care Research, Department of Primary Health Care, University of Oxford, Oxford, UK.
Diabet Med. 2011 Oct;28(10):1182-7. doi: 10.1111/j.1464-5491.2011.03341.x.
Renin-angiotensin inhibitors in Type 2 diabetes and microalbuminuria reduce renal and cardiovascular risk, but evidence supporting use of maximal tolerated dose is unclear. We aimed to determine the extent of renin-angiotensin inhibitor dose-dependent effects from randomized trials carried out in a clinical setting.
In a meta-analysis of randomized clinical trials, alternate doses of angiotensin receptor blockers or angiotensin converting enzyme inhibitors in patients with Type 2 diabetes and microalbuminuria were compared. MEDLINE, EMBASE and the Cochrane Register of Controlled Trials were searched from January 2006 to August 2010. Trials prior to January 2006 were identified from a prior systematic review. Identified outcomes were albumin excretion rate, progression and regression of albuminuria and adverse events.
Four trials including 1051 patients compared doses of angiotensin receptor blockers. No trials compared doses of angiotensin converting enzyme inhibitor. The percentage decline in albumin excretion rate from baseline was greater with higher doses (18% higher, 95% CI 8-28%), the regression to normoalbuminuria was greater (OR 1.66, 95% CI 1.22-2.27), with less progression to macroalbuminuria (OR 0.62, CI 0.38-1.02). Adverse events were fewer with lower-dose angiotensin receptor blockers (OR 1.32, 95% CI 0.90-1.92).
Higher-dose compared with lower-dose angiotensin receptor blockers in Type 2 diabetes with microalbuminuria are associated with significantly reduced albumin excretion rate and increased regression to normoalbuminuria. Adverse events are more frequent, but not significantly so. There is potential for trials to determine clinical cardiovascular and renal outcomes at differing doses. Our findings support current recommendations to titrate renin-angiotensin inhibitors to maximum dose whilst considering risk of adverse side effects with higher doses.
血管紧张素受体阻滞剂（ARB）和血管紧张素转换酶抑制剂（ACEI）在 2 型糖尿病合并微量白蛋白尿患者中降低肾脏和心血管风险，但最大耐受剂量的获益证据尚不明确。本研究旨在确定临床试验中血管紧张素抑制剂剂量依赖性的作用程度。
我们对 2 型糖尿病合并微量白蛋白尿患者的随机临床试验进行了荟萃分析，比较了 ARB 或 ACEI 的不同剂量。检索 2006 年 1 月至 2010 年 8 月 MEDLINE、EMBASE 和 Cochrane 对照试验注册库。2006 年 1 月之前的试验来自之前的系统评价。确定的结局包括尿白蛋白排泄率、白蛋白尿的进展和缓解以及不良事件。
四项包含 1051 例患者的试验比较了 ARB 的剂量。没有试验比较 ACEI 的剂量。较高剂量组的尿白蛋白排泄率从基线的下降百分比更大（高 18%，95%CI 8-28%），正常白蛋白尿的缓解更大（OR 1.66，95%CI 1.22-2.27），向大量白蛋白尿的进展更少（OR 0.62，95%CI 0.38-1.02）。低剂量 ARB 的不良事件更少（OR 1.32，95%CI 0.90-1.92）。
与低剂量 ARB 相比，2 型糖尿病合并微量白蛋白尿患者使用高剂量 ARB 可显著降低尿白蛋白排泄率，并增加正常白蛋白尿的缓解。不良事件更常见，但无统计学意义。有潜力进行试验以确定不同剂量下的临床心血管和肾脏结局。我们的发现支持当前将血管紧张素受体抑制剂滴定至最大剂量的建议，同时考虑较高剂量的不良反应风险。
