Safety and efficacy of sacubitril/valsartan for prevention of anthracycline-related cardiotoxicity: A meta-analysis of randomized controlled trials.

e24010 Background: Anthracycline chemotherapy is a cornerstone of therapy for breast cancer and multiple other malignancies, but its clinical utility is limited by cardiac dysfunction related to cancer therapy (CTRCD). CTRCD is characterized by a decrease in left ventricular ejection fraction (LVEF) with observed rates of asymptomatic cardiac dysfunction in up to 20–30% and overt heart failure (HF) in 5–10% of patients. No standard drug regimen has been established to prevent this. Sacubitril/valsartan (S/V) is widely used to improve outcomes in HFrEF and has been evaluated in recent randomized controlled trials (RCTs) for its potential cardioprotective role in patients receiving anthracycline chemotherapy. In this study, we analyzed RCT data to evaluate the safety and efficacy of S/V for preventing CTRCD in anthracycline-treated patients. Given the lack of established pharmacologic prevention strategies, synthesizing emerging RCT data on S/V may help clarify its potential role in mitigating CTRCD risk. Methods: PubMed, Scopus, ClinicalTrials.gov, and Cochrane Library were searched from inception through January 2026. Eligible studies were RCTs comparing S/V with control (standard care) in patients receiving anthracyclines. CTRCD was defined as ≥15% decline in global longitudinal strain (GLS) or ≥10% absolute LVEF reduction to <50%. Safety analysis focused on hypotension, the most commonly reported adverse event. A random-effects model was used with Revman v5.4, and results with p-values under 0.05 were interpreted as significant. Risk of bias was assessed using the revised Cochrane “Risk of bias” tool for randomized trials (RoB 2.0). Results: Our initial search yielded 12 studies. Three RCTs (SARAH, PRADA II and Hsu et al.), all published in 2025 and enrolling 350 patients in total, met inclusion criteria. Across these trials, S/V significantly reduced CTRCD incidence (RR 0.24, 95% CI 0.10–0.61; I² = 0%; P = 0.003). Hypotension occurred more frequently in the S/V group (RR 4.42, 95% CI 1.59–12.28; I²=0%; P = 0.004). All RCTs were assessed to have low risk of bias. Conclusions: This meta-analysis provides the first synthesis of RCTs evaluating S/V for CTRCD prevention in anthracycline-treated patients, all published in 2025, offering an early evidence base for future trials. S/V significantly reduced the incidence of CTRCD with consistent effects and minimal heterogeneity, supporting its role as a potential strategy for CTRCD prevention. While hypotension was the most reported adverse effect, events were reported as mild and manageable with dose adjustment, underscoring the importance of careful monitoring. Our study is limited by its sample size. Larger multicenter trials powered for long-term clinical outcomes, such as the MAINSTREAM trial projected to complete in 2027, are warranted to confirm or refute these findings.