Statins Linked to Reduced Risk of Mortality in Breast Cancer Patients Treated with Anthracyclines

Tommaso Bucci, MD, PhD
Credit: X.com

An analysis of statin use in patients with breast cancer receiving anthracycline-containing therapies had a lower risk of all-cause mortality than their counterparts not using statin therapy, according to a new study.

A propensity score-matched analysis of the TriNetX database, results of the study suggest use was associated with a reduction in risk of all-cause mortality, but no significant reductions in risk for cardiovascular events, which were examined as a secondary endpoint.¹

“As there has not been any studies investigating the effects of statins in patients with breast cancer treated with anthracyclines, we aimed to investigate the effects of statins in this population,” wrote investigators.¹

As a result of demonstrated efficacy, anthracyclines have established a role as a cornerstone in the treatment of multiple forms cancer. However, revelations of cardiotoxicity create the need for nuanced long-term management discussions for those considering treatment with or who have already received anthracycline-containing therapies.^1,2

Although conducted in a different patient population, the STOP-CA trial from ACC 2023 underlines the interest in addressing cardiotoxicity associated with anthracyclines. In the trial, which examined use of statin therapy in a preventative setting, among 300 patients initiating anthracycline-based chemotherapy. In these patients, initiating atorvastatin 1 year prior to starting anthracycline-based chemotherapy provided cardioprotective benefits, with those not receiving statin therapy at a nearly 3-fold increase in risk of a 10% or greater reduction in left ventricular ejection fraction.2

Approaching the topic from a different perspective, the current study, led by Tommaso Bucci, MD, PhD, and Ying Gue, PhD, both of the Liverpool Centre of Cardiovascular Science at University of Liverpool, leveraged the TriNetX database to identify patients with breast cancer treated with anthracyclines. To obtain the largest patient pool possible, there was no specific period of interest for the search, which was performed on June 01, 2023. However, investigators pointed out more than 95% of patients considered for inclusion within the study entered the database between 2000 and 2020.¹

For the purpose of analysis, participants identified for inclusion were stratified according to presence of statin therapy during the 6 months before first exposure to anthracyclines. Investigators used 1:1 propensity score matching to create their stratified cohorts, with matching based on age, sex, ethnicity, arterial hypertension, ischemic heart diseases, atrial fibrillation, heart failure, dyslipidemia, diabetes, obesity, chronic kidney disease, ischemic stroke, and cardiovascular medications.¹

The initial search yielded cohorts of 3701 and 37,185 patients with breast cancer using statins and not using statins, respectively. Following propensity score matching, 3315 patients were identified for inclusion in each group and investigators noted there were no significant differences between the users and nonusers for all variables considered.¹

The primary outcome of interest for the study was all-cause mortality. The study included multiple secondary outcomes of risk, including acute myocardial infarction, ischemic stroke, atrial fibrillation, ventricular arrhythmias, heart failure, and pulmonary embolism. Investigators used Cox proportional hazard models to calculate hazard ratios (HR) for each outcome based on statin treatment.¹

Upon analysis, results indicated the 5-year cumulative incidences of all-cause death and cardiovascular events were 15.0% and 25.8%, respectively, among statin users and 16.2% and 10.7%, respectively, among nonusers. Further analysis suggested statin use was associated with a reduction in risk of all-cause mortality relative to nonuse (HR, 0.82; 95% CI, 0.74 to 0.91).¹

Analysis of secondary outcomes revealed statin use was associated with an elevated risk of ischemic stroke relative to nonuse (HR, , but no significant difference was found for myocardial infarction (HR, 0.97; 95% CI, 0.75 to 1.26), atrial fibrillation (HR, 1.00; 95% CI, 0.84 to 1.18), ventricular arrhythmias (HR, 0.93; 95% CI, 0.69 to 1.28), heart failure (HR, 1.07; 95% CI, 0.83 to 1.39), and pulmonary embolism (HR, 0.99; 95% CI, 0.83 to 1.18) relative to nonuse.¹

In exploratory analyses assessing risk of new-onset cardiovascular complications among those without a history of such events before anthracycline treatment indicated there were no significant differences in risk for ischemic stroke (HR, 1.11; 95% CI, 0.83 to 1.48), myocardial infarction (HR, 0.95; 95% CI 0.72 to 1.27), atrial fibrillation (HR, 1.02; 95% CI, 0.81 to 1.27), ventricular arrhythmias (HR, 0.88; 95% CI, 0.64 to 1.22), heart failure (HR, 1.05; 95% CI, 0.80 to 1.37), and pulmonary embolism (HR, 1.02; 95% CI, 0.83 to 1.26) among statin users relative to nonusers.¹

Before concluding, investigators called attention to multiple limitations within their study. These included those inherent with observational and retrospective study, reliance on ICD codes to assess outcomes of interest, lack of analysis based on statin dosage, lipid-lowering intensity, and cholesterol levels, and lack of data related to left ventricular strain or ejection fraction, among others.¹

“Statin use was associated with a reduced risk of all-cause death in breast cancer patients treated with anthracycline, supporting the continued use of statins throughout the treatment of breast cancer," investigators wrote.

References:

1. ^{Bucci T, Gue Y, Dobson R, Palmieri C, Pignatelli P, Lip GYH. Statin use is associated with a lower risk of all-cause death in patients with breast cancer treated with anthracycline containing regimens: a global federated health database analysis. Clin Exp Med. 2024;24(1):124. Published 2024 Jun 12. doi:10.1007/s10238-024-01395-z}
2. ^{Neilan TG, Quinaglia T, Onoue T, et al. Atorvastatin for Anthracycline-Associated Cardiac Dysfunction: The STOP-CA Randomized Clinical Trial. JAMA. 2023;330(6):528–536. doi:10.1001/jama.2023.11887}