Statins to prevent early cardiac dysfunction in patients at increased cardiotoxicity risk receiving anthracycline therapy
Innovative Approaches to Care Delivery, Public Health, and Equity, Diversity & Inclusion
The project examined the use of a widely available drug (statin) to reduce the risk of heart dysfunction in patients receiving anthracyline based therapy. Although the drug was well tolerated we did not see benefit of statins compared to placebo in this patient population. This was likely because of the low overall risk of cardiotoxicity in the patients recruited in the study. A companion study performed in Boston in higher risk patients did infact show that statins redcued the risk of cardiotoxicity. The long term follow-up of patients included in our study is ongoing. Therefore, although we did not see an acute benefit of statins, we will soon know whether statins have preventive benefits in longer term follow-up. If our findings show that statins are infact helpful in the longer term, our findings can be easily adopted by any institution globally.
Objectives: Anthracyclines can cause cancer therapy-related cardiac dysfunction (CTRCD). We aimed to assess whether statins prevent decline in left ventricular ejection fraction (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, and 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 = 0.06-0.47), 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 early LVEF decline, LV remodeling, CTRCD, change in serum cardiac biomarkers, or CMR myocardial tissue changes.
Challenges: Recruitment period / follow-up took longer than planned due to COVID-19.
Thavendiranathan P, Houbois C, Marwick TH, Kei T, Saha S, Runeckles K, et al. Statins to prevent early cardiac dysfunction in cancer patients at increased cardiotoxicity risk receiving anthracyclines. Eur Heart J Cardiovasc Pharmacother. 2023 Sep 20;9(6):515-525.