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.

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.