Atorvastatin for prevention of chemotherapy-induced cardiotoxicity: a 5-year propensity-matched cohort study of 800 patients

Background Chemotherapy-induced cardiotoxicity (CTRCD) remains a serious complication in cancer patients, potentially limiting treatment efficacy and affecting survival. While statins have demonstrated cardioprotective effects in randomized trials, evidence on long-term outcomes and optimal dosing across diverse cancer populations is limited. Purpose To evaluate the long-term association between atorvastatin use and incidence of CTRCD in patients receiving potentially cardiotoxic cancer treatments, and to compare the efficacy of 40 mg versus 80 mg daily doses. Methods This retrospective cohort study included 800 patients with breast cancer, lymphoma, multiple myeloma, or sarcoma treated with cardiotoxic chemotherapy (anthracyclines, trastuzumab, or cyclophosphamide) between 2015-2023. Propensity score matching (1:1) was performed using age, sex, cardiovascular risk factors, cancer type, stage, and chemotherapy regimen, yielding 400 atorvastatin users (40-80 mg/day) and 400 non-users. The primary endpoint was CTRCD at 5 years, defined as LVEF reduction ≥10% to absolute value <53% or relative reduction >15% from baseline. Secondary endpoints included heart failure hospitalization, cardiovascular mortality, and echocardiographic changes. Results Baseline characteristics were well-balanced (mean age 58 years, 61% female, mean LVEF 61%). At 5-year follow-up, CTRCD occurred in 62 patients (15.5%) in the atorvastatin group versus 128 patients (32.0%) in controls (HR 0.42; 95% CI 0.31–0.57; p<0.001). Heart failure hospitalizations were reduced (7.0% vs. 13.0%; HR 0.52; 95% CI 0.33–0.82; p=0.005), with a trend toward lower cardiovascular mortality (3.3% vs. 6.0%; HR 0.54; 95% CI 0.29–1.02; p=0.058). LVEF decline was attenuated with atorvastatin (mean change -2.3% vs. -6.6%; p<0.001). No significant difference was observed between atorvastatin 40 mg (16.1%) and 80 mg (14.8%) doses (HR 0.92; 95% CI 0.58–1.45; p=0.72). Results were consistent across cancer types and treatment subgroups. Conclusion In this large propensity-matched cohort with 5-year follow-up, atorvastatin use was associated with significantly reduced incidence of chemotherapy-induced cardiotoxicity across diverse cancer types. The comparable efficacy of 40 mg and 80 mg doses suggests that moderate-intensity statin therapy may be sufficient for cardioprotection, with implications for long-term safety and cost-effectiveness. These real-world findings support and extend evidence from randomized trials, warranting prospective confirmation.