Statins may prevent cardiac dysfunction in patients taking anthracyclines
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NEW ORLEANS — In the STOP-CA trial, prophylactic atorvastatin therapy reduced the occurrence of anthracycline-associated left ventricular dysfunction at 12 months among patients who underwent treatment for Hodgkin and non-Hodgkin lymphoma.
“Anthracyclines are a standard chemotherapy drug used in the treatment of breast cancer and lymphoma. Anthracyclines are prescribed to more than 1 million patients worldwide per year. It has been known for decades that [they] are associated with cardiac toxicity. ... There is an up to 10- to 15-fold increased risk for heart failure with anthracyclines,” Tomas G. Neilan, MD, MPH, director of the cardio-oncology program at Massachusetts General Hospital, said during a presentation at the American College of Cardiology Scientific Session. “Experimental data, retrospective studies and a small randomized trial [have shown] either an attenuation of anthracycline-associated left ventricular dysfunction or a lower rate of clinical heart failure. However, in a recent randomized, multicenter clinical trial, the left ventricular ejection function at 24 months was not different in those randomized to atorvastatin or placebo.”
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Neilan and colleagues conducted the double-blind, randomized, placebo-controlled STOP-CA trial to evaluate the effect of atorvastatin compared with placebo on the occurrence of cardiac dysfunction among patients with lymphoma treated with anthracyclines.
Prior to anthracycline treatment, 300 patients were assigned atorvastatin or placebo for 12 months (mean age, 50 years; 47% women; 89% white). Median cumulative anthracycline dose was 264 mg/m2.
At baseline, the mean LVEF was 63% and declined to 59% at 12 months.
The primary outcome was the proportion of participants with a decline in LVEF of 10% to less than 55%. The 12-month incidence of the primary outcome was 9% in the atorvastatin group compared with 22% in the placebo group (P = .002). The likelihood of decline in cardiac dysfunction after anthracyclines was nearly threefold among patients randomly assigned placebo (OR = 2.9; 95% CI, 1.4-6.4).
At 12 months, 21% of the entire cohort had a decline in LVEF of 5% to less than 55% from baseline. The incidence of this secondary endpoint was 13% in the atorvastatin group compared with 29% in the placebo group (P = .001).
From baseline to 12 months, LVEF decreased 4% compared with 5% in the placebo arm (P = .029).
The researchers observed no difference in HF events between groups (P = .77).
Compared with placebo, atorvastatin was associated with lower incidence of the primary outcome in subgroups including women (P = .024), age older than 52 years (P = .03), patients who received lower cumulative anthracycline treatment (< 250 mg/m2; P = .011) and patients with BMI of at least 30 kg/m2 (P = .019).
There were no between-group differences in adverse events.
“Among study participants with lymphoma being treated with anthracyclines, the use of atorvastatin over 12 months is associated with a lower rate of cardiac systolic dysfunction,” Neilan said. “These data support the use of atorvastatin among patients with lymphoma being treated with anthracyclines where prevention of cardiac systolic dysfunction is important.”
Perspective
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The most important take-home message from the STOP-CA trial is that statins potentially could help attenuate the drop in the EF among patients exposed to anthracyclines for lymphoma.
Unfortunately, with anthracyclines, which patients need to treat their malignancy in lymphoma or breast cancer, sometimes there are off-target effects, such as damage to the heart muscle. We've been trying to find ways to attenuate the drop in EF and eventual HF events.
What it means for patients is that potentially there may be a push to start high-dose statins — such as atorvastatin 40 mg in this trial — to attenuate that drop in EF.
What we don't know from STOP-CA, and what I think most cardiologists will be wanting from this and looking forward prospectively in further studies, is will this also amount to a reduction in HF events? There is a dichotomy there in what this implies, more so in patients receiving placebo vs. those receiving atorvastatin; we didn't necessarily measure the actual HF syndrome, event, hospitalization or quality of life, here. That is very different from what we interpret on an echocardiogram. Ultimately, the magnitude of difference in the mean EF between two arms is only 1%, which frankly is not that much in terms of clinical meaning.
The future is bright though. If we continue to conduct well-performed studies looking at agents that could help attenuate the drop in EF, we may one day find also a therapy that stops a drop in EF that may result in reduction of HF events, but ultimately will also be associated with a reduction in HF events and overall improvement in survival and quality of life for our patients afflicted with these malignancies.
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Scherrer-Crosbie M, et al. Joint American College of Cardiology/Journal of the American College of Cardiology Late-Breaking Clinical Trials. Presented at: American College of Cardiology Scientific Session; March 4-6, 2023; New Orleans (hybrid meeting).
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