Sydney School of Public Health, The University of Sydney, Sydney, Australia.
Nephrology, Dialysis and Transplantation Unit, Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy.
Cochrane Database Syst Rev. 2024 Apr 29;4(4):CD006257. doi: 10.1002/14651858.CD006257.pub2.
BACKGROUND: Guidelines suggest that adults with diabetes and kidney disease receive treatment with angiotensin-converting-enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARB). This is an update of a Cochrane review published in 2006. OBJECTIVES: We compared the efficacy and safety of ACEi and ARB therapy (either as monotherapy or in combination) on cardiovascular and kidney outcomes in adults with diabetes and kidney disease. SEARCH METHODS: We searched the Cochrane Kidney and Transplants Register of Studies to 17 March 2024 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Registry Platform (ICTRP) Search Portal, and ClinicalTrials.gov. SELECTION CRITERIA: We included studies evaluating ACEi or ARB alone or in combination, compared to each other, placebo or no treatment in people with diabetes and kidney disease. DATA COLLECTION AND ANALYSIS: Two authors independently assessed the risk of bias and extracted data. Summary estimates of effect were obtained using a random-effects model, and results were expressed as risk ratios (RR) and their 95% confidence intervals (CI) for dichotomous outcomes and mean difference (MD) or standardised mean difference (SMD) and 95% CI for continuous outcomes. Confidence in the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. MAIN RESULTS: One hundred and nine studies (28,341 randomised participants) were eligible for inclusion. Overall, the risk of bias was high. Compared to placebo or no treatment, ACEi may make little or no difference to all-cause death (24 studies, 7413 participants: RR 0.91, 95% CI 0.73 to 1.15; I = 23%; low certainty) and with similar withdrawals from treatment (7 studies, 5306 participants: RR 1.03, 95% CI 0.90 to 1.19; I = 0%; low certainty). ACEi may prevent kidney failure (8 studies, 6643 participants: RR 0.61, 95% CI 0.39 to 0.94; I = 0%; low certainty). Compared to placebo or no treatment, ARB may make little or no difference to all-cause death (11 studies, 4260 participants: RR 0.99, 95% CI 0.85 to 1.16; I = 0%; low certainty). ARB have uncertain effects on withdrawal from treatment (3 studies, 721 participants: RR 0.85, 95% CI 0.58 to 1.26; I = 2%; low certainty) and cardiovascular death (6 studies, 878 participants: RR 3.36, 95% CI 0.93 to 12.07; low certainty). ARB may prevent kidney failure (3 studies, 3227 participants: RR 0.82, 95% CI 0.72 to 0.94; I = 0%; low certainty), doubling of serum creatinine (SCr) (4 studies, 3280 participants: RR 0.84, 95% CI 0.72 to 0.97; I = 32%; low certainty), and the progression from microalbuminuria to macroalbuminuria (5 studies, 815 participants: RR 0.44, 95% CI 0.23 to 0.85; I = 74%; low certainty). Compared to ACEi, ARB had uncertain effects on all-cause death (15 studies, 1739 participants: RR 1.13, 95% CI 0.68 to 1.88; I = 0%; low certainty), withdrawal from treatment (6 studies, 612 participants: RR 0.91, 95% CI 0.65 to 1.28; I = 0%; low certainty), cardiovascular death (13 studies, 1606 participants: RR 1.15, 95% CI 0.45 to 2.98; I = 0%; low certainty), kidney failure (3 studies, 837 participants: RR 0.56, 95% CI 0.29 to 1.07; I = 0%; low certainty), and doubling of SCr (2 studies, 767 participants: RR 0.88, 95% CI 0.52 to 1.48; I = 0%; low certainty). Compared to ACEi plus ARB, ACEi alone has uncertain effects on all-cause death (6 studies, 1166 participants: RR 1.08, 95% CI 0.49 to 2.40; I = 20%; low certainty), withdrawal from treatment (2 studies, 172 participants: RR 0.78, 95% CI 0.33 to 1.86; I = 0%; low certainty), cardiovascular death (4 studies, 994 participants: RR 3.02, 95% CI 0.61 to 14.85; low certainty), kidney failure (3 studies, 880 participants: RR 1.36, 95% CI 0.79 to 2.32; I = 0%; low certainty), and doubling of SCr (2 studies, 813 participants: RR 1.14, 95% CI 0.70 to 1.85; I = 0%; low certainty). Compared to ACEi plus ARB, ARB alone has uncertain effects on all-cause death (7 studies, 2607 participants: RR 1.02, 95% CI 0.76 to 1.37; I = 0%; low certainty), withdrawn from treatment (3 studies, 1615 participants: RR 0.81, 95% CI 0.53 to 1.24; I = 0%; low certainty), cardiovascular death (4 studies, 992 participants: RR 3.03, 95% CI 0.62 to 14.93; low certainty), kidney failure (4 studies, 2321 participants: RR 1.15, 95% CI 0.67 to 1.95; I = 29%; low certainty), and doubling of SCr (3 studies, 2252 participants: RR 1.18, 95% CI 0.85 to 1.64; I = 0%; low certainty). Comparative effects of different ACEi or ARB and low-dose versus high-dose ARB were rarely evaluated. No study compared different doses of ACEi. Adverse events of ACEi and ARB were rarely reported. AUTHORS' CONCLUSIONS: ACEi or ARB may make little or no difference to all-cause and cardiovascular death compared to placebo or no treatment in people with diabetes and kidney disease but may prevent kidney failure. ARB may prevent the doubling of SCr and the progression from microalbuminuria to macroalbuminuria compared with a placebo or no treatment. Despite the international guidelines suggesting not combining ACEi and ARB treatment, the effects of ACEi or ARB monotherapy compared to dual therapy have not been adequately assessed. The limited data availability and the low quality of the included studies prevented the assessment of the benefits and harms of ACEi or ARB in people with diabetes and kidney disease. Low and very low certainty evidence indicates that it is possible that further studies might provide different results.
背景:指南建议糖尿病合并肾脏疾病的成年人接受血管紧张素转换酶抑制剂(ACEi)或血管紧张素受体阻滞剂(ARB)治疗。这是对 2006 年发表的 Cochrane 综述的更新。 目的:我们比较了 ACEi 和 ARB 治疗(无论是单药治疗还是联合治疗)在糖尿病合并肾脏疾病患者中的心血管和肾脏结局的疗效和安全性。 检索方法:我们通过使用与本次综述相关的检索词,于 2024 年 3 月 17 日之前检索了 Cochrane 肾脏和移植组注册研究。通过对 CENTRAL、MEDLINE 和 EMBASE、会议论文集、国际临床试验注册平台(ICTRP)检索门户和 ClinicalTrials.gov 的检索,确定了注册研究。 入选标准:我们纳入了评估 ACEi 或 ARB 单独或联合与安慰剂或不治疗相比在糖尿病合并肾脏疾病患者中的疗效和安全性的研究。 数据收集和分析:两名作者独立评估了偏倚风险并提取了数据。使用随机效应模型获得效应的汇总估计值,结果表示为风险比(RR)及其 95%置信区间(CI)用于二分类结局,以及均数差(MD)或标准化均数差(SMD)及其 95%CI 用于连续结局。使用推荐评估、制定和评估(GRADE)方法评估证据的可信度。 主要结果:共有 109 项研究(28341 名随机参与者)符合纳入标准。总体而言,偏倚风险较高。与安慰剂或不治疗相比,ACEi 可能对全因死亡(24 项研究,7413 名参与者:RR 0.91,95%CI 0.73 至 1.15;I²=23%;低确定性)和相似的治疗退出(7 项研究,5306 名参与者:RR 1.03,95%CI 0.90 至 1.19;I²=0%;低确定性)几乎没有或没有影响。ACEi 可能预防肾衰竭(8 项研究,6643 名参与者:RR 0.61,95%CI 0.39 至 0.94;I²=0%;低确定性)。与安慰剂或不治疗相比,ARB 可能对全因死亡(11 项研究,4260 名参与者:RR 0.99,95%CI 0.85 至 1.16;I²=0%;低确定性)几乎没有或没有影响。ARB 对治疗退出(3 项研究,721 名参与者:RR 0.85,95%CI 0.58 至 1.26;I²=2%;低确定性)和心血管死亡(6 项研究,878 名参与者:RR 3.36,95%CI 0.93 至 12.07;低确定性)的影响不确定。ARB 可能预防肾衰竭(3 项研究,3227 名参与者:RR 0.82,95%CI 0.72 至 0.94;I²=0%;低确定性)、血清肌酐(SCr)翻倍(4 项研究,3280 名参与者:RR 0.84,95%CI 0.72 至 0.97;I²=32%;低确定性)和微量白蛋白尿进展为大量白蛋白尿(5 项研究,815 名参与者:RR 0.44,95%CI 0.23 至 0.85;I²=74%;低确定性)。与 ACEi 相比,ARB 对全因死亡(15 项研究,1739 名参与者:RR 1.13,95%CI 0.68 至 1.88;I²=0%;低确定性)、治疗退出(6 项研究,612 名参与者:RR 0.91,95%CI 0.65 至 1.28;I²=0%;低确定性)、心血管死亡(13 项研究,1606 名参与者:RR 1.15,95%CI 0.45 至 2.98;I²=0%;低确定性)、肾衰竭(3 项研究,837 名参与者:RR 0.56,95%CI 0.29 至 1.07;I²=0%;低确定性)和 SCr 翻倍(2 项研究,767 名参与者:RR 0.88,95%CI 0.52 至 1.48;I²=0%;低确定性)的影响不确定。与 ACEi 加 ARB 相比,ACEi 单药治疗对全因死亡(6 项研究,1166 名参与者:RR 1.08,95%CI 0.49 至 2.40;I²=20%;低确定性)、治疗退出(2 项研究,172 名参与者:RR 0.78,95%CI 0.33 至 1.86;I²=0%;低确定性)、心血管死亡(4 项研究,994 名参与者:RR 3.02,95%CI 0.61 至 14.85;低确定性)、肾衰竭(3 项研究,880 名参与者:RR 1.36,95%CI 0.79 至 2.32;I²=0%;低确定性)和 SCr 翻倍(2 项研究,813 名参与者:RR 1.14,95%CI 0.70 至 1.85;I²=0%;低确定性)的影响不确定。与 ACEi 加 ARB 相比,ARB 单药治疗对全因死亡(7 项研究,2607 名参与者:RR 1.02,95%CI 0.76 至 1.37;I²=0%;低确定性)、治疗退出(3 项研究,1615 名参与者:RR 0.81,95%CI 0.53 至 1.24;I²=0%;低确定性)、心血管死亡(4 项研究,992 名参与者:RR 3.03,95%CI 0.62 至 14.93;低确定性)、肾衰竭(4 项研究,2321 名参与者:RR 1.15,95%CI 0.67 至 1.95;I²=29%;低确定性)和 SCr 翻倍(3 项研究,2252 名参与者:RR 1.18,95%CI 0.85 至 1.64;I²=0%;低确定性)的影响不确定。比较不同 ACEi 或 ARB 和低剂量与高剂量 ARB 的效果的研究很少评估。没有研究比较不同剂量的 ACEi。ACEi 和 ARB 的不良反应很少报告。 作者结论:与安慰剂或不治疗相比,ACEi 或 ARB 对糖尿病合并肾脏疾病患者的全因和心血管死亡可能没有或几乎没有影响,但可能预防肾衰竭。ARB 可能与安慰剂或不治疗相比,预防 SCr 翻倍和微量白蛋白尿进展为大量白蛋白尿。尽管国际指南建议不联合使用 ACEi 和 ARB 治疗,但 ACEi 或 ARB 单药治疗与双重治疗相比的效果尚未得到充分评估。纳入研究的数量有限且质量较低,这阻止了评估 ACEi 或 ARB 在糖尿病合并肾脏疾病患者中的益处和危害。低和非常低确定性证据表明,进一步的研究可能会提供不同的结果。
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