Key Points
-Anthracycline therapy is associated with the development of heart failure, yet anthracyclines are among the most widely used and most effective antineoplastics.
-Limiting the cumulative dose of anthracycline, when possible, and screening for cardiotoxicity with echocardiograms should be standard practice.
-In the STOP-CA study, in patients with lymphoma treated with anthracyclines, the prophylactic use of atorvastatin over 12 months was associated with a lower rate of left ventricular dysfunction compared to placebo.
Anthracyclines, which are used to treat a variety of cancers, are associated with the development of heart failure. Despite their widespread use, a safe and effective pharmacologic prophylaxis against cardiotoxicity has proved elusive. Screening with echocardiography and limiting cumulative doses of the medication remains the standard of care.
Studies examining the effect of statin use and the risk of heart failure in cancer patients are conflicting. Although statins are best known for their effect on lowering cholesterol through blocking HMG-CoA reductase, they may also be protective against damage to cardiac myocytes caused by anthracyclines.
The results of STOP-CA trial (NCT02943590), a randomized, doubled-blind, placebo control study, evaluating the effectiveness of atorvastatin in preventing heart failure in patients with non-hodgkins and Hodgkins lymphoma treated with anthracycline was presented by Dr. Tomas Neilen, the study’s co-lead author (Massachusetts General Hospital) at the ACC 2023 Conference today.
The primary endpoint was the proportion of patients with a 10% reduction in left ventricular ejection fraction (LVEF) or more (to less than 55%, near the lower limit of normal LVEF) from baseline to one year. A total of 300 participants were enrolled with half assigned to take atorvastatin 40 mg daily and the other a placebo. Subjects with pre-existing statin use or a left ventricular ejection fraction less than 50% at baseline were excluded. The baseline LVEF for the entire cohort was 63±4.6% at baseline and 59±5.9% at 12 months.
At twelve months, the incidence of the primary endpoint was 9% in the atorvastatin group and 22% in the placebo group (p=0.002). There was a 1.3% higher LVEF at 12 months between patients treated with atorvastatin compared to placebo (p0.029) but no significant difference in heart failure events.
Another secondary endpoint was the proportion of patients with a smaller, 5% decrease in LVEF. Similar to the primary outcome, it occurred more frequently in the placebo group (29% vs. 13%, p=0.001). A subset of patients underwent cardiac MRI that also demonstrated a significant difference in LVEF between the atorvastatin and placebo group.
An exploratory subgroup analysis found a significant difference in the change in LVEF in patients who were female, aged 52 years or older, received a cumulative anthracycline dose of 250mg/m² or greater, or had a BMI ≥ 30. There were no significant differences in adverse events, including muscle pain, between the two groups.
In conclusion, this randomized, placebo controlled trial found that atorvastatin was cardioprotective in patients with lymphoma treated with an anthracycline. Further studies are needed to assess which subgroups of patients may benefit most from statin use and examine whether statin therapy prevents symptomatic heart failure.