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

Abstract

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.

The angiotensin receptor and neprilysin inhibitor, LCZ696, in heart failure: A meta-analysis of randomized controlled trials

“…The meta-analysis showed that LCZ696 was superior to ACEis and ARBs in improving the overall mortality, rate of hospitalizations for HF, decline in renal function, and reduction in NT-proBNP levels in patients with HF. These results were consistent with those in Huang et al’s study, [ 27 ] in which it was reported that compared with ACEI/ARB, LCZ696 decreased the risk of death, discontinuation due to AEs, and decline in renal function. Moreover, Kang et al [ 28 ] reported that LCZ696 significantly increased the estimated glomerular filtration rate ( P = .02) and reduced the NT-proBNP level ( P < .001) compared with irbesartan, valsartan, and enalapril.…”

Effects of sacubitril/valsartan on life quality in chronic heart failure: A systematic review and meta-analysis of randomized controlled trials

“…Several other studies supported that sacubitril/valsartan was associated with the reduction of the apnea burden in patients with HFrEF and the improvement of blood glucose control in patients with CHF and diabetes ( 14 , 15 ). In terms of safety, sacubitril/valsartan has a lower risk of renal impairment and severe hyperkalemia, and does not increase the risk of severe angioedema compared with ACEI/ARB, but the risk of hypotension is slightly higher ( 16 ).…”

Our Experience With Sacubitril/Valsartan in Chronic Heart Failure Management - HFrEF in the Ambulatory Setting

“…These drugs serve as the foundations of pharmacotherapy for patients with HFrEF. Therefore, it is recommended that an ACE-I or ARB is replaced by sacubitril/valsartan in ambulatory patients with HFrEF, who remain symptomatic despite optimal medical treatment ( 1 - 6 ).…”

“…The 2021 ESC published guidelines recommends the use of ARNI as a replacement for ACE-I in suitable patients who remain symptomatic on ACE-I, beta-blocker, and MRA therapies; however, an ARNI may be considered as a first-line therapy instead of an ACE-I - (Class of Recommendation 1B) in reducing the risks of cardiovascular death and hospitalization ( 1 ). In addition, a meta-analysis provided evidence that sacubitril/valsartan had fewer drug-risks compared with ACEIs/ARBs, such as angioedema, hyperkalemia, cough, dizziness, renal dysfunction and arterial hypotension ( 6 , 7 , 10 - 13 ).…”