Atorvastatin and Myocardial Extracellular Volume Expansion During Anthracycline-Based Chemotherapy

Abstract

Background

In the STOP-CA (Statins to Prevent the Cardiotoxicity From Anthracyclines) trial, atorvastatin preserved the left ventricular ejection fraction among patients with lymphoma treated with anthracyclines. The protective mechanisms are currently unclear.

Objectives

The aim of this study was to test the effect of atorvastatin on the anthracycline-associated increase in myocardial extracellular volume (ECV) using cardiac magnetic resonance imaging (MRI).

Methods

Cardiac MRI with mapping was performed at baseline and at 12-month follow-up. ECV was calculated, and the primary endpoint was a ≥3% increase. Increases of ≥1 SD in native T1 and T2 times and ECV were secondary endpoints.

Results

The subgroup included 171 participants with paired cardiac MRI scans, and 127 had contrast scans of appropriate quality (median age 52 years, 47% women). The proportion of participants with ≥3% increases in ECV was lower in the atorvastatin compared with the placebo group (8% vs 29%; P = 0.002; OR: 0.20; 95% CI: 0.06 to 0.59). A ≥3% increase in ECV was associated with an 8.4% decrease in left ventricular ejection fraction at follow-up (95% CI: −6.31 to −10.38; P < 0.001). The proportion of participants with ≥1-SD increases in T1 and T2 times was statistically similar between groups at 12 months. At 24 months, there were fewer heart failure events among those without ≥3% increases in ECV (8% vs 24%; P = 0.054), though not statistically significantly.

Conclusions

Compared with placebo, atorvastatin limited ECV expansion among participants with lymphoma undergoing anthracycline chemotherapy. This study is the first to provide mechanistic insight into statins’ cardioprotective effects with anthracyclines. (Statins to Prevent the Cardiotoxicity From Anthracyclines [STOP-CA]; NCT02943590)