Timing of sacubitril/valsartan initiation and cardiovascular outcomes in anthracycline-treated cancer patients

Background Anthracycline-induced cardiotoxicity remains a major limitation in cancer therapy. While sacubitril/valsartan (S/V) has demonstrated benefits in heart failure, the impact of timing of initiation on outcomes in anthracycline-treated patients is not well established. Purpose To evaluate whether early initiation of S/V after anthracycline exposure is associated with improved cardiovascular outcomes compared with delayed initiation. Methods We conducted a retrospective cohort study using the TriNetX global health research network. Cancer patients receiving anthracycline therapy and treated with S/V were identified and stratified by early initiation (≤30 days after chemotherapy) versus delayed initiation (>30 days). Propensity score matching (1:1) was performed to adjust for demographics, comorbidities, cancer type, and concomitant therapies. The primary outcome was a composite of all-cause mortality and heart failure at 5 years. Secondary outcomes included biomarkers, ICU admission, and echocardiographic parameters. Results After matching, 842 patients were included in each group. Early S/V initiation was associated with lower 5-year mortality (HR 0.78; 95% CI 0.65–0.94; p=0.01) and reduced incidence of heart failure (HR 0.82; 95% CI 0.69–0.98; p=0.03) compared with delayed initiation. Biomarker trajectories were similar between groups, and no significant differences were observed in ICU admission. Conclusion Early initiation of sacubitril/valsartan following anthracycline therapy was associated with improved long-term cardiovascular outcomes. These findings suggest that timing of neurohormonal modulation may play a critical role in mitigating anthracycline-related cardiotoxicity and warrant prospective evaluation.