Statins to prevent early cardiac dysfunction in cancer patients at increased cardiotoxicity risk receiving anthracyclines

Abstract

Background and Aims Anthracyclines can cause cancer therapy related cardiac dysfunction (CTRCD). We aimed to assess whether statins prevent decline in LVEF in anthracycline-treated patients at increased risk for CTRCD. Methods In this multicenter double-blinded, placebo-controlled trial, patients with cancer at increased risk of anthracycline-related CTRCD (per ASCO guidelines) were randomly assigned to atorvastatin 40 mg or placebo once-daily. Cardiovascular magnetic resonance (CMR) imaging was performed before and within 4 weeks-after anthracyclines. Blood biomarkers were measured at every cycle. The primary outcome was post-anthracycline LVEF, adjusted for baseline. CTRCD was defined as a fall in LVEF by > 10% to < 53%. Secondary endpoints included left ventricular (LV) volumes, CTRCD, CMR tissue characterization, high sensitivity troponin I (hsTnI), and B-type natriuretic peptide (BNP). Results We randomized 112 patients (56.9 ± 13.6 years, 87 female, 73 with breast cancer): 54 to atorvastatin and 58 to placebo. Post-anthracycline CMR was performed 22 (13–27) days from last anthracycline dose. Post-anthracycline LVEF did not differ between the atorvastatin and placebo groups (57.3 ± 5.8% and 55.9 ± 7.4%, respectively) when adjusted for baseline LVEF (p = 0.34). There were no significant between-group differences in post-anthracycline LV end-diastolic (p = 0.20) or end-systolic volume (p = 0.12), CMR myocardial edema and/or fibrosis (p = 0.06 to 0.47), or peak hsTnI (p ≥ 0.99) and BNP (p = 0.23). CTRCD incidence was similar (4% versus 4%, p ≥ 0.99). There was no difference in adverse events. Conclusions In patients at increased risk of CTRCD, primary prevention with atorvastatin during anthracycline therapy did not ameliorate LVEF decline, LV remodeling, CTRCD, change in serum cardiac biomarkers, or CMR myocardial tissue changes. Trial registration: NCT03186404.

Prevention and treatment of anthracycline-induced cardiotoxicity: A bibliometric analysis of the years 2000–2023

“…And the incidence of cardiotoxicity can be reduced regardless of the type of statin used, suggesting that there is no difference between types of statins [ 77 ]. However, it has also been pointed out that statins do not have a significant role in changing LVEF, which may be related to the short observation time [ 78 ]. In conclusion, statins are effective in preventing anthracycline-induced cardiotoxicity, but the selection of the appropriate dose and duration of treatment during statin therapy still needs to be explored in large-sample clinical trials.…”

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