Sacubitril/Valsartan and cardiovascular outcomes in cancer patients on anthracycline therapy: a global health research network retrospective analysis

Anthracyclines (AC) are essential in cancer therapy but significantly increase the risk of cardiotoxicity, particularly heart failure. Preclinical studies suggest that sacubitril/valsartan (S/V) may mitigate doxorubicin-induced cardiotoxicity through various molecular mechanisms.

We aim to assess the impact of S/V on cardiovascular outcomes in cancer patients undergoing AC therapy using the TriNetX global health research network.

A retrospective cohort study was conducted using the TriNetX Network in patients with cancer under AC therapy, comparing S/V treatment with no treatment after a chemotherapy session. Propensity Score Matching (PSM) at a 1:1 ratio was used for balancing the confounders between S/V users and non-users, accounting for demographics, medical conditions, medications, and psychosocial covariates. The primary outcomes included BNP, troponin, echocardiographic parameters, and chronic heart failure, while the secondary outcomes - mortality and Intensive Care Unit admission - were analyzed at 5 years follow-up. Cumulative incidence for binary endpoints calculated using Cox Proportional-Hazard methods was reported as Hazard Ratio (HR) and 95% Confidence Interval (95%CI), and continuous endpoints in mean and standard deviation (SD). All analyses were calculated using TriNexT software.

After PSM, 1,231 cancer patients treated with AC received S/V, while 1,231 did not. At baseline, the S/V group BNP levels (1,347 ± 3,790 vs. 1,166 ± 6,667 pg/mL; p = 0.76) and troponin levels (2.47 ± 20.7 vs. 0.16 ± 0.69 ng/mL; p = 0.38). At 5 years, S/V groups non-S/V had no significant difference in BNP (p = 0.95; Table 1) and troponin levels (p = 0.57; Table 1). The echocardiographic outcome was similar between the groups. Both systolic and diastolic chronic heart failure were higher in the intervention group: HR 38.71 ([95% CI: 25.26-59.31]), and HR 7.71 ([95% CI: 5.03-11.81]), respectively. However, mortality rates in 5 years were lower in the S/V group, with a HR 0.843 ([95% CI: 0.71–0.99]; p= 0.04; Fig.1), and ICU admission was not statistically significant.

Sacubitril/Valsartan showed no significant impact on BNP, troponin, or echocardiographic parameters in cancer patients receiving anthracycline therapy but was associated with reduced 5-year all-cause mortality, suggesting potential long-term benefits.