The use of atorvastatin prior to anthracycline-based chemotherapy in lymphoma patients reduces the subsequent development of cardiac dysfunction, according to the findings of a randomised trial.
Provision of the cholesterol lowering drug atorvastatin before starting anthracycline-based chemotherapy for the treatment of lymphoma, lowered the risk of developing a reduction in left ventricular ejection fraction.
Published in the journal JAMA, the study was designed to test whether atorvastatin was associated with a reduction in the proportion of patients with lymphoma receiving anthracyclines who develop cardiac dysfunction.
The Statins to Prevent the Cardiotoxicity of Anthracyclines, STOP-CA trial, was a multicentre, double-blind, randomised, placebo-controlled trial of 40 mg daily of atorvastatin administered to patients receiving anthracyclines for lymphoma. It enrolled lymphoma patients who were scheduled to receive anthracycline-based chemotherapy, but it excluded those already treated with a statin or who had clinical indication for a statin.
Prior to chemotherapy, all participants underwent a baseline assessment of heart rate, blood pressure, weight, blood tests and left ventricular ejection fraction (LVEF). Individuals were then randomised in a 1:1 ratio to receive oral atorvastatin or placebo, commencing prior to the first scheduled anthracycline infusion and then continued for 12 months. Echocardiographic measures of LVEF were performed on anonymised images in a core laboratory at the University of Pennsylvania.
The primary endpoint was the proportion of participants in each group with an absolute decline in LVEF of 10% or greater from prior to chemotherapy to a final value of less than 55% over the 12-month study period.
A secondary endpoint was the proportion of participants with an absolute decline in LVEF of ≥5% from prior to chemotherapy to a final value of <55% over 12 months.
Atorvastatin and decline in LVEF
Of the 300 participants, 286 completed the trial. Among the entire cohort, the baseline mean LVEF was 63% and the follow-up LVEF was 58%.
At the 12-month follow-up, the incidence of the primary endpoint was 9% in the atorvastatin group and 22% in the placebo group (p = 0.002). The researchers calculated that the odds of a 10% or greater decline in LVEF to a final value of less than 55% after anthracycline treatment was almost three times greater for participants randomised to placebo (odds ratio, OR = 2.9 95% C 1.4 – 6.4).
In addition, compared with placebo, atorvastatin also reduced the incidence of the secondary endpoint (13% vs 29%; p = 0.001). The number of serious related adverse events was low and similar between groups.
Based on the results, the authors wrote that these finding may support the use of atorvastatin in patients with lymphoma at high risk of cardiac dysfunction due to anthracycline use.