Efficacy and Safety of Angiotensin-Converting Enzyme Inhibitors in Combination with Angiotensin-Receptor Blockers in Nondiabetic Chronic Kidney Disease: A Systematic Review and Meta-Analysis

Abstract

Background: It is unclear whether angiotensin-converting enzyme inhibitors (ACEIs) in combination with angiotensin-receptor blockers (ARBs) are superior to ACEIs or ARBs alone in the treatment of nondiabetic chronic kidney disease (CKD). The present meta-analysis was designed to assess the efficacy and safety of ACEIs in combination with ARBs in nondiabetic CKD.

Methods: The PubMed, Embase, and Cochrane Library databases were searched to identify randomized controlled trials (RCTs) published prior to March 2020. A random-effects model was used to calculate the effect sizes of eligible studies.

Results: The present meta-analysis of 20 RCTs encompassing 1,398 patients with nondiabetic CKD demonstrated that ACEIs in combination with ARBs were superior to ACEIs or ARBs alone in reducing urine albumin excretion (SMD, -0.69; 95% CI, -1.13 to -0.25; P=0.002), urine protein excretion (SMD, -0.34; 95% CI, -0.46 to -0.23; P<0.001), and blood pressure (systolic blood pressure: WMD, -1.43; 95% CI, -2.42 to -0.44; P=0.005; diastolic blood pressure: WMD, -1.85; 95% CI, -2.67 to -1.04; P<0.001) without decreasing glomerular filtration rate (SMD, -0.07; 95% CI, -0.20 to 0.06; P=0.30) or increasing incidences of hyperkalaemia (RR, 1.70; 95% CI, 0.47 to 6.11; P=0.42) and hypotension (RR, 1.80; 95% CI, 0.67 to 4.86; P=0.25).

Conclusion: Compared with ACEIs or ARBs alone, ACEIs in combination with ARBs are effective and safe in the treatment of nondiabetic CKD. ACEIs combined with ARBs may be a better choice to reduce proteinuria as long as they can be tolerated.

Keywords: ACEIs in combination with ARBs; blood pressure; hyperkalaemia; hypotension.; nondiabetic chronic kidney disease; urine protein excretion; urine albumin excretion.