Sacubitril/valsartan for the prevention of cancer therapy-related cardiac dysfunction: a systematic review and meta-analysis

INTRODUCTION: Sacubitril/valsartan is being investigated for cardiac protection during cancer therapy. However, evidence regarding its preventive effect on cancer therapy–related cardiac dysfunction (CTRCD) remains inconsistent. AIMS: To evaluate the efficacy and safety of sacubitril/valsartan for the prevention of CTRCD during oncologic therapy. METHODS AND RESULTS: We searched PubMed, EMBASE, and Web of Science for randomized controlled trials (RCTs) comparing sacubitril/valsartan with control for the prevention of CTRCD during oncologic therapy, with treatment effects synthesized using risk ratio (RR), mean differences (MD), or standardized mean differences (SMD) with 95% confidence intervals. Four RCTs involving 410 participants were included. Sacubitril/valsartan reduced the absolute risk of CTRCD compared with control (RR 0.66, 95% CI 0.53 to 0.82, p < 0.001). Sacubitril/valsartan was associated with a significant improvement in left ventricular ejection fraction (MD 1.19%, 95% CI 0.05 to 2.33, p = 0.045), global longitudinal strain (SMD 0.43, 95% CI 0.10 to 0.75, p = 0.026), and a reduction in troponin (log-MD − 0.43, 95% CI − 0.59 to − 0.26, p < 0.001), compared with the control group. Sacubitril/valsartan increased the risk of hypotension (RR 4.75, 95% CI 1.78 to 12.63, p = 0.002). No significant differences were observed in left ventricular volume, work indices, or NT-proBNP levels. Trial sequential analysis indicated that the current evidence remains insufficient to draw firm conclusions regarding the effect of cardioprotection on CTRCD. CONCLUSION: Sacubitril/valsartan may be associated with modest reductions in CTRCD risk and attenuation of LVEF and GLS decline in patients with preserved baseline cardiac function receiving chemotherapy. However, the clinical relevance remains inconclusive when considering the trial sequential analysis and the modest magnitude of effect. These findings are primarily hypothesis-generating rather than practice-changing, and require confirmation in larger randomized trials, particularly in higher-risk populations.