Adverse Events of Sacubitril/Valsartan: A Meta-analysis of Randomized Controlled Trials

This review aimed to summarize the adverse events (AEs) reported during the use of sacubitril/valsartan versus angiotensin converting enzyme inhibitors (ACEI)/angiotensin II receptor blocker (ARB). Studies containing safety outcomes or AEs during the use of sacubitril/valsartan versus ACEI/ARB were retrieved from the MEDLINE, Embase, and Cochrane Library databases and clinical trials. From the selected studies, the pooled risk ratios with 95% confidence intervals of dichotomous outcomes were assessed by a random or fixed effects model in our meta-analysis. Fourteen studies involving 20,261 patients were included in this review. No significant differences were found in total AEs between the sacubitril/valsartan and ACEI/ARB groups. Compared with ACEI/ARB, sacubitril/valsartan decreased the risk of death, discontinuation due to AEs, and renal dysfunction, whereas it increased the risk of hypotension. Specifically, sacubitril/valsartan decreased the risk of death compared with ACEI/ARB, whereas it increased the risk of hypotension for patients with heart failure and decreased the risk of discontinuation due to AEs in White patients. It also increased the risk of dizziness in Asians and decreased the risk of hyperkalemia and renal dysfunction, whereas it increased the risk of hypotension when the study duration was ≥48 weeks. The available evidence showed that sacubitril/valsartan was associated with fewer side effects than ACEI/ARB, except for hypotension. Study duration, race, and patients with primary diseases affected the AEs of sacubitril/valsartan.