Atorvastatin May Mitigate Risk of Cardiac Events Due to Anthracycline Use in Lymphoma

Starting treatment with atorvastatin prior to anthracycline-based chemotherapy for lymphoma may reduce the risk of developing cardiac dysfunction due to anthracycline use, according to results from the Statins to Prevent the Cardiotoxicity of Anthracyclines (STOP-CA) trial (NCT02943590) published in JAMA.¹

Anthracyclines are widely used to treat hematological and solid-tumor cancers, including lymphoma. However, past research suggests the use of anthracyclines may be associated with late cardiac effects, including heart failure, among patients with lymphoma.²

Prior research also suggests that statins may help preserve cardiac function in patients treated with anthracyclines, the study authors noted. Considering such findings, the randomized, double-blind, placebo-controlled STOP-CA trial aimed to determine the utility of atorvastatin in patients with lymphoma at a high risk of late cardiac effects due to anthracycline treatment.

Three hundred patients scheduled to undergo anthracycline-based chemotherapy for lymphoma at 9 academic medical centers in the United States were randomized to receive either atorvastatin at a dosage of 40 mg per day (n = 150) or a placebo (n = 150) starting prior to chemotherapy and continuing for 12 months. The main outcome was the percentage of patients who experienced an absolute decline in left ventricular ejection fraction (LVEF) of 10% or greater from before chemotherapy to a final value of less than 55% over after 12 months. The proportion of patients who experienced a 5% or greater decline in LVEF to a final value of less than 55% over 12 months was a secondary outcome.

At baseline, the mean LVEF was 63% in the overall cohort, and mean follow-up LVEF was 58%. Among participants, study drug adherence was noted in 91%.

Forty-six patients (15%) experienced a decline in LVEF of 10% or greater and showed a final value of less than 55%. In the atorvastatin group, 9% of patients experienced such a decline compared with 22% in the placebo group (P = .002). Patients in the placebo group also were nearly 3 times more likely to experience a 10% or greater decline in LVEF to a final value of 55% or lower (odds ratio [OR], 2.9; 95% CI, 1.4-6.4). Incidence of the secondary end point was also higher in the placebo group vs the atorvastatin group (29% vs 13%, respectively; P = .001).

The rates of incident heart failure were 3% in the atorvastatin cohort and 6% in the placebo group, but the difference was not statistically significant (P = .26). Both groups also had low and similar numbers of serious adverse events.

The study was limited using LVEF as a surrogate for heart failure development, but the authors note that the end point was a substantial change in LVEF that was beyond measurement variability and consistent with guideline recommendations. STOP-CA also did not enroll a population that was racially or ethnically diverse, meaning the findings may not be generalizable to the overall population. Whether treatment with different doses or lengths of time would have an effect is also unknown, the authors noted.

Still, the findings suggest that prophylactic atorvastatin over 12 months was associated with a lower rate of cardiac dysfunction due to anthracycline treatment. “These data support the use of atorvastatin among patients being treated with anthracyclines, in whom prevention of cardiac systolic dysfunction is important,” the authors concluded.

Reference

1. Neilan TG, Quinaglia T, Onoue T, et al. Atorvastatin for anthracycline-associated cardiac dysfunction: the STOP-CA randomized clinical trial. JAMA. 2023;330(6):528-536. doi:10.1001/jama.2023.11887

2. Limat S, Demesmay K, Voillat L, et al. Early cardiotoxicity of the CHOP regimen in aggressive non-Hodgkin’s lymphoma. Ann Oncol. 2003;14(2):277-281. doi:10.1093/annonc/mdg070