Atorvastatin Reduces Anthracycline-Associated Cardiotoxicity

In a recent study published in JAMA, atorvastatin reduced cardiac functional impairment for patients with lymphoma who were treated with anthracyclines.

Although many clinical trials and real-world study data corroborate the efficacy of anthracyclines, these medications have significant cardiotoxicity and may lead to cardiac injury. In this context, the STOP-CA clinical trial, conducted by a multidisciplinary team led by Tomas G. Neilan, MD, associate professor of medicine at Harvard in Boston, sought to assess whether use of atorvastatin is associated with a reduction in the proportion of patients with lymphoma who are receiving anthracyclines and who develop cardiac dysfunction.

North American Population

The double-blind, randomized, and placebo-controlled clinical trial included 300 adult patients aged 18 years and older with lymphoma. The patients originated from nine academic medical centers in the United States and Canada. Enrollment occurred between January 25, 2017, and September 10, 2021, with final follow-up on October 10, 2022.

Participants were randomly assigned in a 1:1 ratio to receive atorvastatin 40 mg or placebo by mouth daily. The protocol was initiated before the first administration of anthracycline-based chemotherapy and continued over 12 months.

The primary outcome was the proportion of participants with an absolute decline in left ventricular ejection fraction (LVEF) of 10% or more from before chemotherapy to a final value of less than 55% over 12 months. A secondary outcome was the proportion of participants with an absolute decline in LVEF of 5% or more from before chemotherapy to a final value of less than 55% over 12 months.

Baseline assessment of participants was based on data obtained by checking the heart rate, blood pressure, body weight, blood tests, and LVEF. The latter was mainly measured using MRI of the heart. However, because part of the study was conducted during the COVID-19 pandemic, some oncology patients did not have access to this test. These patients received an echocardiogram.

The mean age of the participants was 50 years (standard deviation [SD], 17), and 54% were aged 50 or older. Of the 300 participants, 220 (73%) had non-Hodgkin lymphoma, and 80 (37%) had Hodgkin lymphoma. All were treated with anthracyclines. A total of 286 (95%) participants completed the clinical trial.

Among the entire cohort, the baseline mean LVEF was 63% (SD, 4.6%), and the follow-up LVEF was 58% (SD, 5.7%) Overall, 91% of participants complied with the atorvastatin treatment schedule.

Lack of Diversity

At 12-month follow-up, 46 (15%) patients demonstarted a decline in LVEF of 10% or greater from before undergoing chemotherapy to a final value of less than 55%. The incidence of the primary endpoint was 9% (13/150) in the atorvastatin group and 22% (33/150) in the placebo group (P = .002). According to the data, the odds of a 10% or greater decline in LVEF to a final value of less than 55% after anthracycline treatment was almost three times greater for participants who received placebo, compared with those who received atorvastatin (odds ratio, 2.9) Compared with placebo, atorvastatin also reduced the incidence of the secondary endpoint (13% vs 29%; P = .001).

It is important to note that there were 13 adjudicated heart failure (HF) events (4%) over 24 months of follow-up. There was no difference in the rates of incident HF between study groups (3% with atorvastatin and 6% with placebo; P = .26). The number of serious related adverse events was low and was similar between groups.

Regarding the study’s limitations, although 50% of the study population was female, there was no racial or ethnic diversity in the cohort. Also, in the STOP-CA study, atorvastatin was administered only at a dosage of 40 mg/day. Therefore, it was not possible to assess any potential effects with other doses or treatment durations.

Reducing Cardiotoxicity

Anthracyclines treat a broad range of cancers and play an essential role in the anticancer therapy armamentarium. However, anthracycline-associated cardiotoxicity requires careful assessment in some cases. The risk of anthracycline-associated cardiac events is dose dependent. The risk is also higher among patients at elevated cardiovascular risk and varies according to the type of cancer.

During the 12 months of the STOP-CA study, 1 in 6 participants who were treated with anthracyclines experienced an initial decline in LVEF of 10% or greater. This decline resembles that observed in similar trials in which the decrease often caused an increased risk of clinical HF.

The authors wrote that the design of the trial was not intended to reveal why statins offered protection against anthracycline-associated cardiotoxicity. Although these mechanisms are unclear, the data suggest that anthracyclines cause oxidative damage to heart cells.

According to the scientists, the interventions proposed in the study were safe and did not affect hemodynamic parameters such as blood pressure. Moreover, they emphasized that statins do not pose a risk to oncology patients.

Repercussions in Practice

Considering how complex the field of oncology is, choosing a treatment is often challenging, especially when the risk of adverse events is high. In the case of lymphoma, the study shows that atorvastatin may help reduce the risk of cardiac dysfunction caused by anthracycline use. This finding may support the use of atorvastatin along with anthracyclines to reduce cardiovascular risk.

This article was translated from the Medscape Portuguese Edition.

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