Chemotherapy-related cardiac dysfunction (CTRCD) remains a major limitation of cardiotoxic cancer therapies, with limited preventive strategies available. Global longitudinal strain (GLS) enables early detection of myocardial injury, yet effective cardioprotective interventions remain limited.

This systematic review and meta-analysis of randomized controlled trials, published in The American Journal of Cardiology, evaluated the association of angiotensin receptor–neprilysin inhibitor (ARNI) therapy, specifically sacubitril/valsartan, with cardiac outcomes in patients undergoing chemotherapy.

A comprehensive search of PubMed, Embase, and Cochrane databases identified randomized controlled trials comparing ARNI therapy with control. Four trials involving 412 participants were included, with 42.7% receiving ARNI and follow-up ranging from 6 to 18 months.

Outcomes included left ventricular ejection fraction (LVEF), global longitudinal strain (GLS), CTRCD incidence, all-cause mortality, NT-proBNP levels, dyspnea, and safety endpoints. Effect estimates were expressed as risk ratios (RRs) for binary outcomes and mean differences (MDs) for continuous variables.

ARNI therapy was associated with higher left ventricular systolic function (MD 1.47% [95% confidence interval (CI): 0.59 to 2.34]) and less GLS deterioration (MD −0.93% [95% CI: −1.49 to −0.38]) compared with control. No significant differences were observed in CTRCD incidence (RR 0.40 [95% CI: 0.08 to 1.97]) or all-cause mortality (RR 0.63 [95% CI: 0.08 to 5.01]). ARNI therapy was associated with increased risk of hypotension, while no significant effects were observed for NT-proBNP levels or dyspnea.

These findings indicate that ARNI therapy was associated with preservation of cardiac function during chemotherapy, without significant differences in CTRCD or mortality, while highlighting hypotension as a key safety consideration.