Effects of renin–angiotensin system blockers on renal and cardiovascular outcomes in patients with diabetic nephropathy: a meta-analysis of randomized controlled trials
This study aimed to evaluate the effect f angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB) on renal or cardiovascular outcomes in patients with diabetic nephropathy (DN).
PubMed, Embase, and Cochrane Library were searched for randomized controlled trials (RCTs) evaluating the treatment effects of ACEI and ARB on renal or cardiovascular outcomes in patients with DN until August 2017. The outcomes included end-stage renal disease (ESRD), doubling of serum creatinine levels, all-cause mortality, major cardiovascular events (MACEs), myocardial infarction (MI), stroke, and cardiac death. Relative risks (RR) with 95% confidence intervals (CIs) were used for calculating the summary results using a random-effects model.
Twenty-four RCTs including 57,818 patients with DN and 891 events of ESRD, 1050 doubling of serum creatinine concentration, 4352 all-cause mortality, 6342 MACEs, 1073 MI, 2900 stroke, and 1674 cardiac deaths were reported. Overall, the summary results suggested that in patients with DN, receiving ACEI did not have a significant effect on ESRD, doubling of serum creatinine levels, all-cause mortality, MI, stroke, and cardiac death, while ACEI significantly reduced the risk of total MACEs. Furthermore, ARB therapy was associated with a low risk of ESRD and doubling of serum creatinine levels, while it did not differ significantly on all-cause mortality, MACEs, MI, stroke, and cardiac death in patients with DN.
Patients with DN receiving ACEI had significantly reduced the risk of total MACEs, and ARB could reduce the incidence of ESRD and the doubling of serum creatinine levels.
KeywordsDiabetic nephropathy ACEI ARB Meta-analysis
Compliance with ethical standards
Conflict of interest
All authors declare that they have no conflict of interests.
- 2.IDF Diabetes Atlas, 9th edition 2019. https://diabetesatlas.org/en/resources/. Retrieved 2 Dec 2019
- 3.(2019) Introduction: standards of medical care in diabetes-2019. Diabetes Care 42:S1–S2. https://doi.org/10.2337/dc19-Sint01
- 13.Deeks JJ, Higgins JPT, Altman DG (2008) Analyzing data and undertaking meta-analyses. In: Higgins JP, Green S (eds) Cochrane Handbook for Systematic Reviews of Interventions. The Cochrane Collaboration, Oxford, p 501Google Scholar
- 16.Tobias A (1999) Assessing the influence of a single study in meta-analysis. Stata Tech Bull 47:15–17Google Scholar
- 23.Laffel LM, McGill JB, Gans DJ (1995) The beneficial effect of angiotensin-converting enzyme inhibition with captopril on diabetic nephropathy in normotensive IDDM patients with microalbuminuria. North American Microalbuminuria Study Group. Am J Med 99:497–504PubMedCrossRefPubMedCentralGoogle Scholar
- 24.Maschio G, Alberti D, Janin G, Locatelli F, Mann JF et al (1996) Effect of the angiotensin-converting-enzyme inhibitor benazepril on the progression of chronic renal insufficiency. The Angiotensin-Converting-Enzyme Inhibition in Progressive Renal Insufficiency Study Group. N Engl J Med 334:939–945PubMedCrossRefPubMedCentralGoogle Scholar
- 27.(2000) Effects of ramipril on cardiovascular and microvascular outcomes in people with diabetes mellitus: results of the HOPE study and MICRO-HOPE substudy. Heart outcomes prevention evaluation study investigators. Lancet 355:253–259Google Scholar
- 29.Marre M, Lievre M, Chatellier G, Mann JF, Passa P et al (2004) Effects of low dose ramipril on cardiovascular and renal outcomes in patients with type 2 diabetes and raised excretion of urinary albumin: randomised, double blind, placebo controlled trial (the DIABHYCAR study). BMJ 328:495PubMedPubMedCentralCrossRefGoogle Scholar
- 30.Patel A, Grop AC, MacMahon S, Chalmers J, Neal B et al (2007) Effects of a fixed combination of perindopril and indapamide on macrovascular and microvascular outcomes in patients with type 2 diabetes mellitus (the ADVANCE trial): a randomised controlled trial. Lancet 370:829–840PubMedCrossRefGoogle Scholar
- 38.Bilous R, Chaturvedi N, Sjolie AK, Fuller J, Klein R et al (2009) Effect of candesartan on microalbuminuria and albumin excretion rate in diabetes: three randomized trials. Ann Intern Med 151(11–20):W13–14Google Scholar