Efficacy of angiotensin receptor–neprilysin inhibitor (ARNI) for prevention of cancer therapy–related cardiac dysfunction: A meta-analysis of randomized controlled trials.

Abstract

e24182 Background: Cancer therapy-related cardiac dysfunction (CTRCD) is a clinically significant complication of anticancer treatments, including anthracyclines and trastuzumab, often necessitating dose reduction or discontinuation of potentially life-saving therapy. While angiotensin receptor-neprilysin inhibitors (ARNI) have demonstrated mortality and hospitalization benefits in heart failure with reduced ejection fraction, their efficacy in preventing chemotherapy-induced cardiotoxicity remains controversial due to conflicting results and a lack of large-scale data. Therefore, we performed a meta-analysis to evaluate the efficacy of ARNI for the prevention of cardiotoxicity in patients receiving chemotherapy. Methods: We searched PubMed, Embase, and Cochrane Central from intercept till 17 December 2025 for studies evaluating the benefit of ARNI in preventing CTRCD among patients undergoing cardiotoxic cancer therapy. The primary outcomes assessed were changes in left ventricular ejection fraction (LVEF), global longitudinal strain (GLS), N-terminal pro-brain natriuretic peptide (NT-proBNP), and troponin T. Statistical analysis was performed using Review Manager, and heterogeneity was assessed using the I2 statistic. The study protocol was registered with PROSPERO (CRD420251266270). Results: A total of 442 patients from four RCTs were included, with follow-up periods ranging from 6 to 18 months. The analysis of changes in LVEF showed a trend toward improvement (mean difference 1.18; 95% CI -0.04 to 2.40; p = 0.06), though this did not reach statistical significance. There were no statistically significant differences observed in changes in GLS (mean difference -0.94; 95% CI -2.43 to 0.55; p = 0.14), NT-proBNP (mean difference -0.94; 95% CI -9.57 to 7.70; p = 0.69), or troponin T (mean difference 0.06; 95% CI -1.13 to 1.26; p = 0.92). Conclusions: In conclusion, prophylactic treatment with ARNI in patients undergoing cardiotoxic cancer therapy did not result in statistically significant changes in LVEF, GLS, or cardiac biomarkers (NT-proBNP and troponin T), although a non-significant trend toward preserved LVEF was observed. The lack of statistical significance may be attributable to limited statistical power due to small sample sizes and heterogeneity across cancer therapies. Given the observed trend in LVEF preservation, further adequately powered, large-scale RCTs focusing on specific chemotherapy regimens are needed.