Atorvastatin cardioprotective in lymphoma patients receiving anthracycline?

Among patients with lymphoma receiving anthracycline-based chemotherapy, those who received atorvastatin for 12 months were significantly less likely to experience a cardiac dysfunction than those on placebo, according to the STOP-CA* trial presented at ACC.23/WCC.

“We believe that patients with lymphoma who are treated with anthracyclines and at high risk for cardiac dysfunction and heart failure (HF) would benefit from statin therapy,” said lead author Dr Marielle Scherrer-Crosbie from the Hospital of the University of Pennsylvania.

At 12 months, only 9 percent of patients treated with atorvastatin experienced the primary endpoint of ≥10-percent point reduction from baseline in left ventricle ejection fraction (LVEF) and a decline to a final LVEF value of <55 percent compared with 22 percent in those treated with placebo (p=0.002). This resulted in a nearly threefold risk of cardiac dysfunction in the placebo group (odds ratio, 2.9). [ACC.23/WCC 2023, abstract 402-10]

Significantly fewer patients on atorvastatin had an LVEF decline of ≥5 percent and to <55 percent, the secondary endpoint of the study, than those on placebo (13 percent vs 29 percent; p=0.001).

“This effect will also need to be confirmed in terms of symptomatic HF, but the endpoint we chose is clinically relevant because those rates of decline in LVEF are associated with later symptomatic HF,” said Scherrer-Crosbie.

Dr Tomas Neilan, co-lead author from the Hospital of the University of Pennsylvania in Philadelphia, Pennsylvania, US, who presented the study, pointed out that “anthracyclines are a standard chemotherapy drug used in the treatment of lymphoma … which is a common cancer. Approximately 90,000 patients in the US are diagnosed with lymphoma each year.”

“However, it has been known for decades that anthracyclines are associated with cardiac toxicities,” he noted.

Hence, the researchers conducted a multicentre, double-blind, placebo-controlled trial involving 300 patients with lymphoma (median age 52 years, 47 percent female) who were randomly assigned to receive either atorvastatin 40 mg daily or placebo (n=150 in each group) for 12 months, prior to receiving their first cycle of chemotherapy with anthracycline at a median dose of 300 mg/m². At pre- and post-treatment, LVEF assessment was performed by using cardiac MRI, echocardiogram, and bloodwork.

Among the entire cohort, baseline LVEF was 63 percent, which had declined to 58 percent at 12 months. Fifteen percent of the participants achieved a decline in LVEF of ≥10 percent and then hitting <55 percent.

In an exploratory analysis, the protective effect of atorvastatin on change in LVEF from baseline to 12 months was more pronounced in females and older (median age 52 years) and obese patients (BMI ≥30 kg/m2), as well as those who received anthracyclines at a dose of ≥250 mg/m².

There was no difference in the rate of adverse events, such as muscle pain, elevated liver enzymes, and renal failure. No cases of myositis were reported.

“There is a clear protective effect of atorvastatin in terms of cardiac dysfunction in patients with lymphoma treated with anthracyclines … I think this is an impactful study that will lead to more prescription of statins in patients,” Scherrer-Crosbie said.

“The data support the use of atorvastatin among patients with lymphoma being treated with anthracyclines where prevention of cardiac dysfunction is important,” Neilan added.

*STOP-CA: Statins TO Prevent the Cardiotoxicity associated with Anthracyclines