Atorvastatin for Anthracycline-Associated Cardiac Dysfunction
Authors: Neilan Tomas G. , Quinaglia Thiago , Onoue Takeshi , Mahmood Syed S. , Drobni Zsofia D. , Gilman Hannah K. , Smith Amanda , Heemelaar Julius C. , Brahmbhatt Priya , Ho Jor Sam , Sama Supraja , Svoboda Jakub , Neuberg Donna S. , Abramson Jeremy S. , Hochberg Ephraim P. , Barnes Jefferey A. , Armand Philippe , Jacobsen Eric D. , Jacobson Caron A. , Kim Austin I. , Soumerai Jacob D. , Han Yuchi , Friedman Robb S. , Lacasce Ann S. , Ky Bonnie , Landsburg Dan , Nasta Sunita , Kwong Raymond Y. , Jerosch-Herold Michael , Redd Robert A. , Hua Lanqi , Januzzi James L. , Asnani Aarti , Mousavi Negareh , Scherrer-Crosbie Marielle 
Published: August 2023

Importance

Anthracyclines treat a broad range of cancers. Basic and retrospective clinical data have suggested that use of atorvastatin may be associated with a reduction in cardiac dysfunction due to anthracycline use.

Objective

To test whether atorvastatin is associated with a reduction in the proportion of patients with lymphoma receiving anthracyclines who develop cardiac dysfunction.

Design, Setting, and Participants

Double-blind randomized clinical trial conducted at 9 academic medical centers in the US and Canada among 300 patients with lymphoma who were scheduled to receive anthracycline-based chemotherapy. Enrollment occurred between January 25, 2017, and September 10, 2021, with final follow-up on October 10, 2022.

Interventions

Participants were randomized to receive atorvastatin, 40 mg/d (n = 150), or placebo (n = 150) for 12 months.

Main Outcomes and Measures

The primary outcome was the proportion of participants with an absolute decline in left ventricular ejection fraction (LVEF) of ≥10% from prior to chemotherapy to a final value of &amp;lt;55% over 12 months. A secondary outcome was the proportion of participants with an absolute decline in LVEF of ≥5% from prior to chemotherapy to a final value of &amp;lt;55% over 12 months.

Results

Of the 300 participants randomized (mean age, 50 [SD, 17] years; 142 women [47%]), 286 (95%) completed the trial. Among the entire cohort, the baseline mean LVEF was 63% (SD, 4.6%) and the follow-up LVEF was 58% (SD, 5.7%). Study drug adherence was noted in 91% of participants. At 12-month follow-up, 46 (15%) had a decline in LVEF of 10% or greater from prior to chemotherapy to a final value of less than 55%. The incidence of the primary end point was 9% (13/150) in the atorvastatin group and 22% (33/150) in the placebo group (P = .002). The odds of a 10% or greater decline in LVEF to a final value of less than 55% after anthracycline treatment was almost 3 times greater for participants randomized to placebo compared with those randomized to atorvastatin (odds ratio, 2.9; 95% CI, 1.4-6.4). Compared with placebo, atorvastatin also reduced the incidence of the secondary end point (13% vs 29%; P = .001). There were 13 adjudicated heart failure events (4%) over 24 months of follow-up. There was no difference in the rates of incident heart failure between study groups (3% with atorvastatin, 6% with placebo; P = .26). The number of serious related adverse events was low and similar between groups.

Conclusions and Relevance

Among patients with lymphoma treated with anthracycline-based chemotherapy, atorvastatin reduced the incidence of cardiac dysfunction. This finding may support the use of atorvastatin in patients with lymphoma at high risk of cardiac dysfunction due to anthracycline use.

Trial Registration

ClinicalTrials.gov Identifier: NCT02943590