Prophylactic administration of atorvastatin (40 mg/day) for 12 months in lymphoma patients treated with anthracyclines was associated with a lower rate of cardiac systolic dysfunction than placebo. Women, people over the age of 52, obese people and patients treated with doses of anthracycline above 250 mg/m² benefited particularly well from the statin.
«These data support the use of atorvastatin in lymphoma patients treated with anthracyclines, where it is important to prevent systolic dysfunction,» concluded Prof.Dr. Tomas Neilan, Massachusetts General Hospital, Boston, from the results of the STOP-CA study he presented at the Annual Scientific Meeting of the American College of Cardiology () in conjunction with the World Congress of Cardiology (WCC) in New Orleans on March 4, 2023 [1].
According to Prof. Dr. Anita Deswal, MD Anderson Cancer Center, Houston, at the ACC press conference, one limitation of the study is that it did not examine the effects of atorvastatin on heart failure. Due to the changes in the left ventricular ejection fraction (LVEF), it could not be concluded that heart failure was prevented. Nevertheless, she thinks the study is useful because lymphoma patients usually receive higher doses of anthracycline than, for example, patients with breast cancer.
Cardiotoxic effect of anthracyclines long known
Neilan explained in his introduction that every year more than 1 millionPeople worldwide are treated with anthracyclines such as doxorubicin, or idarubicin. Their cardiotoxic effect has been known for a long time. It begins with the 1st cycle of chemotherapy, and it increases the risk of developing heart failure by 10 to 15 times.
So far, only dexrazoxane is available for the prevention of anthracycline-induced cardiotoxicity, which is classified as suitable in German Guides.
Experimental data, retrospective studies and a small randomized trial had shown that prophylactic administration of statins was associated with a delay in left ventricular dysfunction or less heart failure.
The STOP-CA (Statins TO Prevent the Cardiotoxicity associated with Anthracyclines) study, funded by the U.S. National Institutes for Health/National Heart and Lung Blood Institute, is a double-blind, placebo-controlled, multicenter, randomized study that evaluated the effect of atorvastatin compared to placebo on the occurrence of cardiac dysfunction in lymphoma patients treated with anthracyclines.
Lymphomas are common tumors, fortunately they have a high survival rate, which makes late toxicities of the therapy increasingly noticeable.
Atorvastatin prevents ejection fraction lowering better than placebo
The STOP-CA study was conducted at 9 centers in the U.S. and Canada.69% of the 300 patients enrolled in the study had B-cell lymphoma, 26% Hodgkin’s lymphoma and 5% T-cell lymphoma. They received an average cumulative dose of anthracycline of 264 mg/m². The study population included nearly 50% women, with nearly 90% of participants white. The primary endpoint was the proportion of patients with a decrease in LVEF from ≥ 10% to less than 55%. The secondary endpoint was the proportion of patients with a decrease from ≥ 5% to less than 55%.
286 participants completed the study. Their left ventricular ejection fraction was 63 ± 4.6% at baseline. After 12 months, the LVEF in the overall group had decreased to 59 ± 5.9%. With 46 participants (15%), the LVEF had fallen by more than 10% to below 55%.
The primary endpoint occurred at 12 months in 9% of participants in the atorvastatin group and 22% in the placebo group (p = 0.002). Thus, the risk of left ventricular dysfunction was almost 3 times higher for the placebo group (odds ratio 2.9).
The secondary endpoint was seen at 12 months in 13% of patients in the atorvastatin group and 19% in the placebo group (p = 0.001).
Exploratory analyses showed that LVEF decreased by 4.1% on average in the atorvastatin group and by 5.4% in the placebo group.The difference in the decrease in LVEF was thus 1.3 percentage points; So it was not very large, but significant (p = 0.029). A total of eleven patients developed heart failure, although the incidence did not differ between the two groups (p = 0.77).
Exploratory subgroup analyses showed that the effect of atorvastatin on LVEF was most pronounced in women (-5.4% atorvastatin vs. -3.1% placebo), in individuals over 52 years of age (-4.4% vs. -6.6%), anthracycline dosage ≥ 250 mg/m² (-4.3% vs. -6.2%) and obese people (-3.0% vs. -5.6%).
Muscle pain, increased liver function tests, myositis and renal dysfunction were no more common with atorvastatin than with placebo. LDL cholesterol decreased by 37% with atorvastatin.
Neilan explained that LVEF served as a surrogate parameter for the development of heart failure because the study was not sufficiently «powered» to investigate an effect of atorvastatin on heart failure.
The study captured the change in LVEF after 12 months.According to Neilan, however, it is unclear whether the beneficial effect of atorvastatin can be further detected at a later date.
This article was originally published on Medscape.de.
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