Sacubitril/Valsartan and Prevention of Chemotherapy-Induced Cardiac Dysfunction: Meta-analysis of Randomized Trials.

Chemotherapy-related cardiac dysfunction (CTRCD) is a major limitation of cardiotoxic cancer therapies. Although global longitudinal strain (GLS) allows early detection of myocardial injury, preventive strategies remain scarce. Angiotensin receptor-neprilysin inhibitors (ARNIs) may offer cardioprotection, but current evidence is limited. We conducted a systematic review and meta-analysis of randomized controlled trials evaluating Sacubitril/Valsartan versus control in patients undergoing chemotherapy. PubMed, Embase, and Cochrane databases were searched. Risk ratios (RRs) and mean differences (MDs) with 95% confidence intervals (CIs) were computed for binary and continuous outcomes. Four randomized controlled trials comprising 412 participants were included; 42.7% received ARNI therapy, with follow-up ranging from 6 to 18 months. Compared with control, ARNI significantly preserved left ventricular systolic function (MD 1.47%, 95% CI 0.59-2.34) and attenuated GLS deterioration (MD -0.93%, 95% CI -1.49 to -0.38). However, ARNI did not significantly reduce the incidence of CTRCD (RR 0.40, 95% CI 0.08-1.97) or all-cause mortality (RR 0.63, 95% CI 0.08-5.01). ARNI increased the risk of hypotension but had no significant effects on NT-proBNP or dyspnea. In conclusion, ARNI therapy improves GLS and left ventricular ejection fraction during chemotherapy but has not yet demonstrated reductions in CTRCD or mortality. Hypotension remains a key safety consideration.