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 current review aimed to study the effectiveness and safety of angiotensin receptor-neprilysin inhibitor (ARNI) combined with sodium–glucose cotransporter-2 (SGLT2) inhibitors versus ARNI or SGLT2 inhibitors monotherapy in patients with heart failure with reduced ejection fraction (HFrEF). Studies containing patients with HFrEF who used ARNI combined with SGLT2 inhibitors versus ARNI or SGLT2 inhibitors alone were retrieved from the Medline, Embase, and Cochrane Library databases. 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. Compared with ARNI monotherapy, the reduction in ARNI combined with SGLT2 inhibitors in a composite of the first hospitalization for heart failure or cardiovascular death was 32%, hospitalization for heart failure was 35% and cardiovascular death was 35%; also all-cause death was 30%, worsening renal function was 35%, respectively, for patients with HFrEF. In addition, compared with SGLT2 inhibitors monotherapy, the reduction in ARNI combined with SGLT2 inhibitors in cardiovascular death was 36% and all-cause death was 28%, respectively, for patients with HFrEF. Although the estimated treatment effect is a 55% increase in volume depletion, overall, ARNI combined with SGLT2 inhibitors might be effective and safe for patients with HFrEF, and volume depletion should be given more attention.
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