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Effects of RAS inhibitors on diabetic retinopathy: a systematic review and meta-analysis.
Lancet Diabetes Endocrinol. 2015 Apr; 3(4):263-74.LD

Abstract

BACKGROUND

Results of several studies have shown a possible beneficial effect of renin-angiotensin system (RAS) inhibitors on diabetic retinopathy, but the findings were contradictory. We did a systematic review and meta-analysis to assess the effect of RAS inhibitors on diabetic retinopathy.

METHODS

We identified relevant publications in PubMed, Embase, Cochrane Library Central Register of Controlled Trials, and abstracts from main annual meetings. Only randomised controlled trials comparing angiotensin-converting enzyme (ACE) inhibitor or angiotensin-receptor blocker (ARB) monotherapy with other antihypertensive drugs or placebo in type 1 or type 2 diabetes were eligible for inclusion in the analysis. The primary outcomes were progression and regression of diabetic retinopathy in all patients and several subgroups. Risk ratios (RRs) with corresponding 95% CIs were pooled. We also did a network meta-analysis to assess the effect of different antihypertensive drugs on diabetic retinopathy by ranking order. This study is registered with the International Prospective Register of Systematic Reviews (PROSPERO), number CRD42013004548.

FINDINGS

21 randomised clinical trials with 13,823 participants were included in the meta-analysis. RAS inhibitors were associated with reduced risk of progression (absolute risk difference -3%, 95% CI -5 to -1; pooled RR 0.87, 95% CI 0.80-0.95; p=0.002) and increased possibility of regression of diabetic retinopathy (8%, 1-16; RR 1.39, 95% CI 1.19-1.61; p=0.00002). In normotensive patients, RAS inhibitors decreased risk of diabetic retinopathy progression (0.81, 0.69-0.94; p=0.007) and increased possibility of regression (1.43, 1.14-1.79; p=0.002). In hypertensive patients, RAS inhibitors were not associated with difference in risk of progression of diabetic retinopathy (0.93, 0.79-1.10; p=0.42) or possibility of diabetic retinopathy regression (2.21, 0.92-5.31; p=0.08). ACE inhibitors were associated with reduced risk of diabetic retinopathy progression (0.84, 0.75-0.94; p=0.002) and higher possibility of disease regression (1.50, 1.20-1.86; p=0.0003). ARBs were associated with a higher possibility of diabetic retinopathy regression (1.32, 1.07-1.61; p=0.008), but had no effect on disease progression (0.92, 0.80-1.06; p=0.25). Network meta-analysis showed the association of antihypertensive drugs with risk of diabetic retinopathy progression was lowest for ACE inhibitors, followed by ARBs, β blockers, calcium channel blockers, and placebo in rank order. The association of antihypertensive drugs with possibility of diabetic retinopathy regression was highest for ACE inhibitors, followed by ARBs, placebo, and calcium channel blockers in rank order.

INTERPRETATION

In patients with diabetes, RAS inhibitors reduce the risk of diabetic retinopathy, and increase the possibility of diabetic retinopathy regression. ACE inhibitors might be better than ARBs for treating diabetic retinopathy, and might exert the most beneficial effect on diabetic retinopathy of all widely used antihypertensive drug classes.

Authors+Show Affiliations

Department of Endocrinology, the Affiliated Hospital of Qingdao University, Qingdao, China.Department of Endocrinology, the Affiliated Hospital of Qingdao University, Qingdao, China.Department of Pathology, Shanghai University of Chinese Medicine, Shanghai, China.Department of Endocrinology, the Affiliated Hospital of Qingdao University, Qingdao, China.Department of Endocrinology, the Affiliated Hospital of Qingdao University, Qingdao, China.Department of Endocrinology, the Affiliated Hospital of Qingdao University, Qingdao, China.Department of Endocrinology, the Affiliated Hospital of Qingdao University, Qingdao, China. Electronic address: nlwang@126.com.

Pub Type(s)

Journal Article
Meta-Analysis
Review
Systematic Review

Language

eng

PubMed ID

25660574

Citation

Wang, Bin, et al. "Effects of RAS Inhibitors On Diabetic Retinopathy: a Systematic Review and Meta-analysis." The Lancet. Diabetes & Endocrinology, vol. 3, no. 4, 2015, pp. 263-74.
Wang B, Wang F, Zhang Y, et al. Effects of RAS inhibitors on diabetic retinopathy: a systematic review and meta-analysis. Lancet Diabetes Endocrinol. 2015;3(4):263-74.
Wang, B., Wang, F., Zhang, Y., Zhao, S. H., Zhao, W. J., Yan, S. L., & Wang, Y. G. (2015). Effects of RAS inhibitors on diabetic retinopathy: a systematic review and meta-analysis. The Lancet. Diabetes & Endocrinology, 3(4), 263-74. https://doi.org/10.1016/S2213-8587(14)70256-6
Wang B, et al. Effects of RAS Inhibitors On Diabetic Retinopathy: a Systematic Review and Meta-analysis. Lancet Diabetes Endocrinol. 2015;3(4):263-74. PubMed PMID: 25660574.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effects of RAS inhibitors on diabetic retinopathy: a systematic review and meta-analysis. AU - Wang,Bin, AU - Wang,Fang, AU - Zhang,Yue, AU - Zhao,Shi-Hua, AU - Zhao,Wen-Juan, AU - Yan,Sheng-Li, AU - Wang,Yan-Gang, Y1 - 2015/02/06/ PY - 2015/2/10/entrez PY - 2015/2/11/pubmed PY - 2016/3/2/medline SP - 263 EP - 74 JF - The lancet. Diabetes & endocrinology JO - Lancet Diabetes Endocrinol VL - 3 IS - 4 N2 - BACKGROUND: Results of several studies have shown a possible beneficial effect of renin-angiotensin system (RAS) inhibitors on diabetic retinopathy, but the findings were contradictory. We did a systematic review and meta-analysis to assess the effect of RAS inhibitors on diabetic retinopathy. METHODS: We identified relevant publications in PubMed, Embase, Cochrane Library Central Register of Controlled Trials, and abstracts from main annual meetings. Only randomised controlled trials comparing angiotensin-converting enzyme (ACE) inhibitor or angiotensin-receptor blocker (ARB) monotherapy with other antihypertensive drugs or placebo in type 1 or type 2 diabetes were eligible for inclusion in the analysis. The primary outcomes were progression and regression of diabetic retinopathy in all patients and several subgroups. Risk ratios (RRs) with corresponding 95% CIs were pooled. We also did a network meta-analysis to assess the effect of different antihypertensive drugs on diabetic retinopathy by ranking order. This study is registered with the International Prospective Register of Systematic Reviews (PROSPERO), number CRD42013004548. FINDINGS: 21 randomised clinical trials with 13,823 participants were included in the meta-analysis. RAS inhibitors were associated with reduced risk of progression (absolute risk difference -3%, 95% CI -5 to -1; pooled RR 0.87, 95% CI 0.80-0.95; p=0.002) and increased possibility of regression of diabetic retinopathy (8%, 1-16; RR 1.39, 95% CI 1.19-1.61; p=0.00002). In normotensive patients, RAS inhibitors decreased risk of diabetic retinopathy progression (0.81, 0.69-0.94; p=0.007) and increased possibility of regression (1.43, 1.14-1.79; p=0.002). In hypertensive patients, RAS inhibitors were not associated with difference in risk of progression of diabetic retinopathy (0.93, 0.79-1.10; p=0.42) or possibility of diabetic retinopathy regression (2.21, 0.92-5.31; p=0.08). ACE inhibitors were associated with reduced risk of diabetic retinopathy progression (0.84, 0.75-0.94; p=0.002) and higher possibility of disease regression (1.50, 1.20-1.86; p=0.0003). ARBs were associated with a higher possibility of diabetic retinopathy regression (1.32, 1.07-1.61; p=0.008), but had no effect on disease progression (0.92, 0.80-1.06; p=0.25). Network meta-analysis showed the association of antihypertensive drugs with risk of diabetic retinopathy progression was lowest for ACE inhibitors, followed by ARBs, β blockers, calcium channel blockers, and placebo in rank order. The association of antihypertensive drugs with possibility of diabetic retinopathy regression was highest for ACE inhibitors, followed by ARBs, placebo, and calcium channel blockers in rank order. INTERPRETATION: In patients with diabetes, RAS inhibitors reduce the risk of diabetic retinopathy, and increase the possibility of diabetic retinopathy regression. ACE inhibitors might be better than ARBs for treating diabetic retinopathy, and might exert the most beneficial effect on diabetic retinopathy of all widely used antihypertensive drug classes. SN - 2213-8595 UR - https://www.unboundmedicine.com/medline/citation/25660574/Effects_of_RAS_inhibitors_on_diabetic_retinopathy:_a_systematic_review_and_meta_analysis_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S2213-8587(14)70256-6 DB - PRIME DP - Unbound Medicine ER -