Sacubitril/valsartan in anthracycline-treated patients: a systematic review and meta-analysis of available evidence
Anthracyclines remain a cornerstone of systemic anticancer therapy but are limited by their well-recognized cardiotoxic potential, which may manifest as cancer therapy–related cardiac dysfunction (CTRCD). Despite increasing emphasis on preventive strategies in cardio-oncology, robust evidence supporting pharmacological cardioprotection is scarce. Sacubitril/valsartan has demonstrated clear benefits in heart failure populations; however, its preventive role in patients exposed to anthracyclines has not been systematically evaluated. We performed a systematic review and meta-analysis of randomized controlled trials assessing sacubitril/valsartan for the prevention of CTRCD in adult patients treated with anthracycline-based chemotherapy (PROSPERO CRD420261278068). PubMed, Embase, Scopus, and the Cochrane Library were searched through December 2025. The primary outcome was CTRCD, defined according to 2022 ESC cardio-oncology guidelines. Secondary outcomes included changes in left ventricular ejection fraction (LVEF), global longitudinal strain (GLS), and symptomatic hypotension. Random-effects models were used as the primary analytical approach. Three randomized trials including 352 patients (mean age 52 ± 9 years; 94% breast cancer) were included. Sacubitril/valsartan was associated with a numerically lower risk of CTRCD that did not reach statistical significance in the random-effects model (RR 0.69, 95% CI 0.38–1.23; p=0.21), while the fixed-effects model showed a significant association favoring sacubitril/valsartan. Directionally favorable but non-significant trends were observed for LVEF and GLS. Sacubitril/valsartan was associated with a higher risk of symptomatic hypotension (RR 4.10, 95% CI 1.46–11.54). This meta-analysis identifies a consistent, hypothesis-generating signal suggesting that sacubitril/valsartan may reduce CTRCD incidence and favorably influence cardiac imaging parameters in anthracycline-treated patients, at the cost of increased symptomatic hypotension. Larger, adequately powered trials are needed to define its role in cardio-oncology prevention strategies.