Statin Co-Administration Is Associated with Subclinical Echocardiographic Alterations and Relative Change Amplitude of Estimated Systolic Pulmonary Artery Pressure After Anthracycline Chemotherapy: A Retrospective Cohort Study

Abstract

Background: Anthracycline-induced cardiotoxicity remains a major clinical challenge in oncology. The association between statin use and pulmonary hemodynamic changes during anthracycline chemotherapy remains largely unexplored. Methods: The primary endpoint was change in left ventricular ejection fraction from baseline to 12 months. Secondary endpoints included changes in left ventricular end-systolic volume index and mean e’ velocity. Exploratory endpoints included changes in other diastolic parameters, all estimated systolic pulmonary artery pressure (SPAP)-derived variables, and the descriptive incidence of cancer therapeutics-related cardiac dysfunction (CTRCD). Analyses included multivariable linear regression, 1:1 propensity score matching with baseline echocardiographic parameters included in the matching model, and multiple imputation for missing SPAP data. Results: After confounder adjustment, statin use was independently associated with a milder decline in mean e’ velocity (β = 0.75 cm/s, 95% CI 0.41 to 1.09, p < 0.001) and a smaller reduction in E/A ratio (β = 0.06, 95% CI 0.01 to 0.11, p = 0.02). No significant between-group difference was observed for adjusted ejection fraction change (β = 0.28%, 95% CI −1.11 to 1.66, p = 0.694). Statin use was associated with lower relative change amplitude of estimated SPAP (β = −4.55%, 95% CI −7.34 to −1.76, p = 0.001), with no significant effect on signed mean change. A descriptive component analysis showed a smaller signed mean change in estimated right atrial pressure in the statin group, with no significant difference in tricuspid regurgitant pressure gradient change. This comparison cannot mathematically decompose the absolute-change SPAP endpoint. The incidence of study-defined CTRCD was numerically lower in the statin group (1.25% vs. 4.8%, OR 0.25, 95% CI 0.05 to 1.28, p = 0.15), but this difference was not statistically significant and the study was underpowered for this clinical endpoint. Conclusions: In this retrospective cohort, concomitant statin therapy was associated with smaller changes in diastolic parameters and lower relative change amplitude of estimated SPAP between baseline and 12 month follow-up. No significant independent association with left ventricular systolic function was observed after multivariable adjustment. These hypothesis-generating findings require confirmation in appropriately powered prospective multicenter studies before any clinical implications can be considered.