Abstract

Contemporary chemotherapy has significantly improved cancer survival, yet cancer therapy-related cardiac dysfunction (CTRCD) remains a major cause of morbidity and mortality. Current cardioprotective strategies often fail to preserve left ventricular (LV) function robustly. Sacubitril/valsartan (Sac/Val) has shown promise in mitigating CTRCD. A comprehensive search was conducted across PubMed, Web of Science, CENTRAL, Scopus, and Google Scholar for randomized controlled trials up to December 2025. The primary outcomes were the incidence of CTRCD and the mean change in LV ejection fraction. Data were pooled using risk ratios (RRs) and mean differences (MDs) with 95% confidence intervals (CIs). PROSPERO: CRD420261280152. Four randomized controlled trials involving 412 patients were included. Sac/Val was associated with a significant preservation of LV ejection fraction [MD: 1.71%, 95% CI (0.73–2.68); P < 0.001] and a greater improvement in global longitudinal strain [MD: ‐0.99, 95% CI (‐1.94 to ‐0.04); P = 0.04] compared to controls. However, there was no significant difference in the incidence of CTRCD [RR: 0.44, 95% CI (0.15–1.32); P = 0.14]. Also, Sac/Val significantly increased the risk of hypotension [RR: 4.35, 95% CI (1.71–11.08); P = 0.001] but showed no significant differences in death ( P = 0.86), heart failure ( P = 0.52), or treatment discontinuation due to adverse events ( P = 0.75). Sac/Val significantly preserves LV function and improves subclinical myocardial global longitudinal strain in patients undergoing chemotherapy. Although it increases the risk of hypotension, its overall safety profile regarding hard outcomes is favorable. Further large-scale trials are needed to assess its impact on long-term clinical cardiotoxicity.