Renal safety and efficacy of angiotensin receptor-neprilysin inhibitor: A meta-analysis of randomized controlled trials

What is known and objective Angiotensin receptor-neprilysin inhibitor (ARNi) therapy has been shown to improve cardiovascular outcomes in the Prospective Comparison of ARNi with angiotensin-converting enzyme inhibitor to Determine the Impact on Global Mortality and Morbidity in Heart Failure (PARADIGM-HF) study. However, the renal safety and efficacy of ARNi remains controversial. This meta-analysis aimed to assess the renal safety and efficacy of angiotensin receptor-neprilysin inhibitor (ARNi). Methods and Results PubMed, EMBASE, the Cochrane Library, Web of Science and Clinicaltrials.gov were searched for randomized controlled trials. Eleven studies that covered 21,716 patients were included. ARNi was superior to angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, in terms of risk of renal dysfunction, estimated glomerular filtration rate (eGFR) decline and elevated serum potassium levels, and higher risk of increase in urine albumin-to-creatinine ratio. However, there was no difference in the probability of hyperkalemia and elevated serum creatinine levels. The incidence of eGFR decrease in patients with chronic kidney disease (CKD) was lower in patients who received ARNi, although ARNi use was not associated with higher risk of renal dysfunction in patients with CKD. What is new and conclusion. Available evidence supports the effectiveness of ARNi on improving renal outcome. Compared with renin-angiotensin-aldosterone system inhibition, ARNi protects against renal impairment, since ARNi users have a lower risk of renal dysfunction and a higher eGFR, without an increased risk of hyperkalemia. However, its benefit for CKD patients still warrants further investigation.