Key result
Sacubitril/valsartan did not significantly reduce cancer therapy-related cardiac dysfunction risk (RR 0.69; 95% CI 0.38-1.23; p=0.21) but significantly increased symptomatic hypotension.
Why the study?
Robust evidence supporting pharmacological cardioprotection with sacubitril/valsartan in anthracycline-treated patients to prevent CTRCD is scarce.
Does sacubitril/valsartan prevent cancer therapy-related cardiac dysfunction in adult patients treated with anthracycline-based chemotherapy?
Meta-Analysis (n=352)
Does sacubitril/valsartan prevent cancer therapy-related cardiac dysfunction in adult patients treated with anthracycline-based chemotherapy?
Sacubitril/valsartan shows a hypothesis-generating but non-significant trend towards preventing anthracycline-induced cardiotoxicity, though it significantly increases the risk of symptomatic hypotension.
Does not support sacubitril/valsartan for CTRCD prevention; leaves open larger trials given hypotension risk.
Background 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. Methods 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. Results 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). Conclusions 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.
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Camilli et al. (2026) conducted a meta-analysis in Anthracycline-treated patients / Cancer therapy-related cardiac dysfunction (n=352). Sacubitril/valsartan was evaluated on Cancer therapy-related cardiac dysfunction (CTRCD) (RR 0.69, 95% CI 0.38-1.23, p=0.21). Sacubitril/valsartan did not significantly reduce cancer therapy-related cardiac dysfunction risk (RR 0.69; 95% CI 0.38-1.23; p=0.21) but significantly increased symptomatic hypotension.
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