Atorvastatin and Left Atrial Function During Anthracycline-based Chemotherapy.

Abstract

Background: Structural and functional abnormalities of the left atrium (LA) predict adverse outcomes such as heart failure and mortality in many patients with heart disease. However, the effect of anthracyclines on LA structural and functional abnormalities remains incompletely characterized. Further, atorvastatin prevented the anthracycline-associated decline in the left ventricular ejection fraction; however, whether atorvastatin protects against anthracycline-associated impairment of LA structure and function is currently unknown.

Methods: In the STOP-CA randomized clinical trial, participants with lymphoma treated with anthracyclines were randomized to placebo (n=150) or atorvastatin (n=150) for 12 months. In post-hoc analyses, CMR-derived LA volumetric and functional measurements (reservoir [GLS], conduit, and booster strain) were measured at baseline and 12 months using feature tracking (FT). The primary endpoint was the difference in the proportion of participants with a ≥1SD decrease in LA GLS between the atorvastatin and placebo groups. The secondary endpoint was a ≥20% relative decrease in LA GLS. Other exploratory endpoints included volume indices and emptying fractions.

Results: Of 300 participants, 158 (mean age 51±16 years, 48% female, 83 with atorvastatin) had paired CMR-derived LA strain and volumetric data at baseline and follow-up. Both groups had similar baseline characteristics and cancer treatment. All LA strain and volumetric measures were similar between the two groups at baseline. Among the placebo group, LA GLS decreased from baseline to follow-up (35.5±8.8 vs. 32.4±8.2%, p=0.007). A ≥1SD absolute decrease in LA GLS (8.8% units) was observed among 24% with atorvastatin and 28% with placebo (p=0.59). Similarly, a ≥20% relative decrease in GLS was observed in 25% vs. 31% (p=0.48). Participants over 50 had an almost 10% (9.9%, 95% confidence interval: -18.75, -1.12) greater relative decrease in LA GLS with anthracyclines. There were no differences between cardiac hospitalization rates with a ≥1SD absolute decrease (5% vs. 8%, p=0.72) in LA GLS at 24 months. Among other indices of LA structure and function, the LA total emptying fraction also decreased from baseline to follow-up, with no differences between groups at follow-up.

Conclusion: Atorvastatin did not attenuate the decline in CMR-derived LA GLS among lymphoma patients undergoing anthracycline-based chemotherapy.

Clinical trial registration: NCT02943590; https://clinicaltrials.gov/study/NCT02943590.