Sacubitril/valsartan and prevention of chemotherapy-induced cardiac dysfunction: meta-analysis of randomized trials

Background 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. Purpose To evaluate the efficacy of sacubitril/valsartan in preventing chemotherapy-related cardiac dysfunction, given the clinical need for early cardioprotection. Methods We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) 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% CIs were computed for binary and continuous outcomes. Results Four RCTs 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 to 2.34; Figure 1A) and attenuated GLS deterioration (MD -0.93%, 95% CI -1.49 to -0.38; Figure 1B). 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 0.08-5.0). ARNI increased the risk of hypotension but had no significant effects on NT-proBNP or dyspnea. Conclusions ARNI therapy improves GLS and LVEF during chemotherapy but has not yet demonstrated reductions in CTRCD or mortality. Hypotension remains a key safety consideration.