Atorvastatin Tied to Cardioprotection for Lymphoma Patients on Anthracyclines

NEW ORLEANS -- Patients with lymphoma on anthracycline-based chemotherapy who took atorvastatin (Lipitor) for a year were less likely to experience cardiac dysfunction, according to the STOP-CA trial.

The trial's primary endpoint was defined as the proportion in each study group who had a decline in left ventricular ejection fraction (LVEF) ≥10% to <55%. Of the 142 patients who completed the study and were in the atorvastatin group, 9% experienced the primary endpoint versus 22% in the placebo group (n=144, P=0.002), reported Marielle Scherrer-Crosbie, MD, PhD, of the Hospital of the University of Pennsylvania in Philadelphia.

Additionally, there were no significant differences in the rates of adverse events, such as muscle pain or renal failure, between the two study groups, she said in a presentation at the American College of Cardiology (ACC) annual meeting.

Scherrer-Crosbie also noted that "there was only a minor difference of 1% in the change in LVEF at 12 months between those randomized to atorvastatin and placebo [P=0.029]," while there were 11 heart failure (HF) events, with no difference in the incidence of HF between study groups (P=0.77).

"We believe that patients with lymphoma who are treated with anthracyclines, and are at high risk of cardiac dysfunction and heart failure, would benefit from statin therapy," Scherrer-Crosbie said at an ACC press conference. "I think it's an impactful study that will lead to more prescription of statins in patients."

Scherrer-Crosbie and colleagues reported that the average pre-treatment LVEF for the atorvastatin group was 63%, while at 12 months, the average LVEF came in at 59%, for a mean decrease of 4%. In the placebo group, those percentages were 63%, 57%, and 5%, respectively. Patient adherence in the trial came in at >90%, they said.

Manesh Patel, MD, of the Duke University School of Medicine in Durham, North Carolina, explained to MedPage Today, that "to date, we don't have a ton of therapies to prevent" anthracycline-associated cardiotoxicity.

Patel, who is an American Heart Association spokesperson, said that if he had a lymphoma patient for whom anthracycline chemotherapy was prescribed, he would first ascertain if they were already on a statin therapy, and "if they didn't have a reason to be on statins prior to getting diagnosed with lymphoma, I'm certainly going to be having the conversation with my oncology colleagues to say 'Are you going to be giving anthracycline? If you are, there's some compelling data here that atorvastatin might prevent left ventricular dysfunction.'"

Patel, who was not involved in the study, called STOP-CA "promising," but said more data were needed on the clinical importance of atorvastatin for cancer outcomes and whether the LV dysfunction seen in the study progressed to symptomatic HF.

Scherrer-Crosbie acknowledged that the study findings "will also need to be confirmed in terms of symptomatic heart failure, but the endpoint we chose is clinically relevant because those rates of decline in LVEF are associated with later symptomatic heart failure."

STOP-CA excluded patients with below-normal LVEF at baseline and patients with an indication for statins. Enrollees had a mean age of around 50, more than half were men, the mean BMI was 28, and the vast majority were white. The lack of a racially or ethnically diverse population was a study limitation, according to the researchers. Patients came from eight tertiary U.S. hospitals along with a single facility in Canada. At the time of enrollment, some patients were on other cardiac medications such as beta blockers and calcium channel blockers. Around 20% had a smoking history. T-cell lymphoma was the most common diagnosis (about 70%).

The mean cumulative anthracycline dose was 264 mg/m². The atorvastatin dose was 40 mg, which was started before anthracyclines and continued for a year. Scherrer-Crosbie told MedPage Today that previous research indicated that the 40-mg dose offered cardioprotection in this patient population. Participants were assessed at 12 months with cardiac imaging. LVEF was evaluated at baseline and at 1 year.

"There is a clear protective effect of atorvastatin in terms of cardiac dysfunction in patients with lymphoma treated with anthracyclines," Scherrer-Crosbie said.

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