Angiotensin converting enzyme inhibitors and angiotensin II receptor antagonists for preventing the progression of diabetic kidney disease

 

Abstract

Background

Angiotensin converting enzyme inhibitors (ACEi) and angiotensin II receptor antagonists (AIIRA) are considered to be equally effective for patients with diabetic kidney disease (DKD), but renal and not mortality outcomes have usually been considered.

Objectives

To evaluate the benefits and harms ACEi and AIIRA in patients with DKD.

Search methods

We searched MEDLINE (1966 to December 2005), EMBASE (1980 to December 2005), the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library issue 4 2005) and contacted known investigators.

Selection criteria

Studies comparing ACEi or AIIRA with placebo or each other in patients with DKD were included.

Data collection and analysis

Two authors independently assessed trial quality and extracted data. Statistical analyses were performed using the random effects model and results expressed as risk ratio (RR) with 95% confidence intervals (CI). Heterogeneity among studies was explored using the Cochran Q statistic and the I² test, subgroup analyses and random effects meta-regression.

Main results

Forty nine studies (12,067 patients) were identified. Thirty eight compared ACEi with placebo, four compared AIIRA with placebo and seven compared ACEi and AIIRA directly. There was no significant difference in the risk of all-cause mortality for ACEi versus placebo (RR 0.91, 95% CI 0.71 to 1.17) and AIIRA versus placebo (RR 0.99, 95% CI 0.85 to 1.17). A subgroup analysis of studies using full-dose ACEi versus studies using half or less than half the maximum tolerable dose of ACEi showed a significant reduction in the risk of all-cause mortality with the use of full-dose ACEi (RR 0.78, 95% CI 0.61 to 0.98). Baseline mortality rates were similar in the ACEi and AIIRA studies. The effects of ACEi and AIIRA on renal outcomes (ESKD, doubling of creatinine, prevention of progression of micro- to macroalbuminuria, remission of micro- to normoalbuminuria) were similarly beneficial. Reliable estimates of effect of ACEi versus AIIRA could not be obtained from the three studies in which they were compared directly because of their small sample size.

Authors' conclusions

Although the survival benefits of ACEi are known for patients with DKD, the relative effects on survival of ACEi with AIIRA are unknown due to the lack of adequate direct comparison studies. In placebo controlled studies, only ACEi (at the maximum tolerable dose, but not lower so-called renal doses) were found to significantly reduce the risk of all-cause mortality. Renal and toxicity profiles of these two classes of agents were not significantly different.

 

Plain language summary

Angiotensin converting enzyme inhibitors and angiotensin II receptor antagonists for preventing the progression of diabetic kidney disease

Kidney disease develops in 25% to 40% of diabetic patients, usually 20 to 25 years after the onset of diabetes. Approximately one third of those with diabetic kidney disease (DKD) will progress to end-stage kidney disease (ESKD) and will require long-term dialysis or possibly receive a kidney transplant. Many patients however may die from associated coronary artery disease or other cardiovascular causes before the onset of ESKD. Antihypertensive drugs have been shown to not only be of benefit to the heart but to also provide kidney protection by slowing the progression of DKD to ESKD. Two drugs in particular have been considered equally effective for patients with DKD - these are angiotensin converting enzyme inhibitors (ACEi) and angiotensin II receptor antagonists (AIIRA). However studies have focused on kidney protection rather than over mortality. The aim of this review was to assess the benefits and harms or ACEI and AIIRA therapy in patients with DKD. Fifty studies (13,215 patients) were identified comparing ACEi to placebo, AIIRA to placebo and ACEi to AIIRA. The risk of death from any cause was not significantly reduced with the use of ACEi versus placebo, AIIRA versus placebo or ACEi versus AIIRA. However when we looked at the studies which used the maximum dose tolerated of ACEi rather than the lower, so-called renal doses, there was a significant reduction in the risk of death due to any cause. We were unable to determine which drug provides better protection due to the lack of head-to-head trials.

 

摘要

背景

血管加壓素轉化酉每阻斷劑 (ACEi) 及乙型血管加壓素受器阻斷劑 (AIIRA) 預防糖尿病腎臟疾病的惡化

ACEi及AIIRA對於糖尿病腎臟疾病 (DKD) 的病患有相同的療效。但這兩者在腎臟以及非死亡率的預後是否相同，則需進一步的探討。

目標

評估ACEi及AIIRA在糖尿病腎臟疾病病患的優缺點。

搜尋策略

我們搜尋MEDLINE (1996年至2005年12月) ，EMBASE (1980年至2005年12月) ，以及CENTRAL (考科藍圖書館2005年第四期) 等資料庫，並聯繫已知的研究者。

選擇標準

所有關於ACEi或AIIRA及安慰劑，或兩者相互比較的研究在糖尿病腎臟疾病的病患上，均納入分析。

資料收集與分析

兩位作者各自獨立評估試驗的品質並且分析資料。統計分析以隨機效果模式進行，且結果以相對風險 (RR) 表示，信賴區間 (CI) 為95% 。不同研究之間的差異性以Cochran Q 統計及I2檢定，子群體分析及隨機影響的次級回歸 (metaregression) 來表現。

主要結論

共有49個研究 (12,067位病患) 被納入統計。其中，38個研究在比較ACEi及安慰劑，4個研究在比較AIIRA及安慰劑，剩下的7個研究則直接比較ACEi及AIIRA。對於所有因素造成之死亡率，在ACEi與安慰劑 (RR 0.91,95% CI 0.71 to 1.17) 及AIIRA與安慰劑的比較 (RR 0.99,95% CI 0.85 to 1.17) 呈現沒有明顯差異。一個子群體分析，比較了使用最大劑量ACEi的研究及使用半量或更少可承受劑量的ACEi的研究，發現使用最大劑量的ACEi (RR 0.78,95% CI 0.61 to 0.98) 能夠明顯的減少因任何原因造成死亡的危險性。死亡率的基準值在ACEi及AIIRA之研究中相類似。對於使用ACEi及AIIRA的腎臟影響 (末期腎臟病ESKD,肌酸酐的倍數成長，預防大或微分子白蛋白尿症的惡化，及微分子白蛋白尿症回復至正常的緩解) ，兩者均同樣有效。由於樣本數的不足，在三個直接比較ACEi及AIIRA影響的研究中，並不能獲得可信的評估。

作者結論

雖然ACEi可以改善糖尿病腎病變病患的存活率，但由於缺乏適當的研究做直接比較，ACEi與AIIRA對於存活率的相對影響仍為未知。在安慰劑對照研究中，只有ACEi (在最大容忍劑量，而非所謂的腎劑量) 被發現可明顯的減少因任何原因造成死亡的危險性。這兩種藥物的腎臟及毒性特徵並無明顯的不同。

翻譯人

本摘要由馬偕醫院賴傳才翻譯。

此翻譯計畫由臺灣國家衛生研究院 (National Health Research Institutes, Taiwan) 統籌。

總結

大約25 – 40% 的糖尿病患在20 – 25年後會出現糖尿病腎病變。將近1/3糖尿病腎病變患者會進展到末期腎病變而需要接受長期透析或腎移植。許多患者在進展到末期腎病變前，就已經死於冠心症或心血管疾病。因此，有一些降壓藥物，不僅對心臟有好處而且還可以提供腎保護效果，而延緩糖尿病腎病變進展到末期腎病變的時間，像是ACEi和AIIRA。由於大部分的研究目標主要是放在腎功能的保護而非死亡率上，而這篇綜論的目的是在比較ACEi和AIIRA之間的優缺點。經由這50個研究 (13,215位病患) 拿來比較ACEi和安慰劑; AIIRA和安慰劑; 以及ACEi和AIIRA。結果發現因任何原因造成死亡的危險性在各種治療之間都沒有差別，但是我們卻發現，如果使用最大容忍劑量的ACEi時，比起低劑量或是所謂的腎劑量，可以明顯改善因任何原因造成死亡的危險性。由於沒有適當的文獻佐證，本篇綜論並無法告訴我們哪一種藥物可以提供較好的保護效果。