Efficacy and safety of dual vs single renin-angiotensin-aldosterone system blockade in chronic kidney disease: An updated meta-analysis of randomized controlled trials.

Background: To lower albuminuria and to achieve blood pressure (BP) goals, dual renin-angiotensin-aldosterone system (RAAS) inhibitors are sometimes used in clinical practice for the treatment of CKD. However, the efficacy and safety of dual RAAS blockade therapy remains controversial.

Methods: PubMed, EMBASE, and Cochrane Library were searched, and random effects model was used to calculate the effect sizes of eligible studies. Potential sources of heterogeneity were detected by meta-regression and subgroup analysis.

Results: The present meta-analysis of 72 randomized controlled trials with 10,296 patients demonstrated that dual RAAS blockade therapy was superior to monotherapy in reducing the urine albumin excretion, urine protein excretion, and BP. These beneficial effects were related to the decrease of glomerular filtration rate, the increase of serum potassium level, and higher rates of hyperkalemia and hypotension. Meanwhile, these effects did not lead to improvements in short-term or long-term outcomes, including doubling of serum creatinine, acute kidney injury, end-stage renal disease, mortality, and hospitalization. Compared with the single therapy, angiotensin-converting enzyme inhibitor (ACEI) in combination with angiotensin-receptor blocker (ARB) was a better dual therapy than ACEI or ARB in combination with renin inhibitor or aldosterone receptor antagonist in decreasing urine albumin excretion, urine protein excretion and BP, and the combination was not associated with a lower glomerular filtration rate.

Conclusion: Compared with the single therapy, ACEI in combination with ARB was a better dual therapy than ACEI or ARB in combination with renin inhibitor or aldosterone receptor antagonist. Although ACEI in combination with ARB was associated with higher incidences of hyperkalemia and hypotension, careful individualized management and potassium binders may further expand its application (PROSPERO number CRD42020179398).