Abstract P4-16-09: Effect of simvastatin on cardiac strain in breast cancer patients receiving anthracycline therapy
Authors: Smith KL , Griffin JM , Tsai H-L , Leathers M , Hays A , Lu D-Y , Zhang Z , Rosner GL , Russell SD , Connolly RM , Jelovac D , Visvanathan K , Wolff AC , Stearns V , Abraham T 
Published: May 2019

Abstract
Background: Cardiac toxicity (CT) is a rare late effect of anthracycline therapy for breast cancer (BC). Statins may attenuate the CT of anthracyclines. Myocardial strain can detect subclinical CT before ejection fraction (EF) declines. Global longitudinal strain (GLS) ≥-19% and relative change (RelΔ) in GLS≥11% predict future decline in EF. We conducted a pilot study to evaluate the effect of simvastatin on GLS in BC patients receiving anthracyclines. Methods: We enrolled women with stage I-III BC planning doxorubicin/cyclophosphamide (AC) x 4. Women with heart disease or taking a statin were excluded. Participants were randomized 1:1 to simvastatin 40 mg daily x 24 weeks (wk) + AC or to AC alone. We performed echo with strain 5 times: baseline (BL), pre-AC#2, 1-3 wk after AC#4, 24 wk after AC #1 and 52 wk after AC#1. The primary endpoint was the mean absolute change (|Δ|) in GLS from BL to 1-3 wk after AC#4. Secondary endpoints included RelΔ in GLS, feasibility and safety. We used two-sample t-tests to compare mean changes in GLS and Fisher's exact test to compare dichotomized GLS values. The study closed early due to loss of staff. Results: Of 31 patients, 15 (48%) received simvastatin+AC. Mean age was 46 years; 71% pre-menopausal, 61% white and 32% black. There were no significant differences in BL cardiovascular risk factors between the arms. After AC, 3 HER2+ patients received trastuzumab. There were no grade 3-4 AEs with simvastatin. Common grade 1-2 AEs included myalgia (20%), elevated AST (27%) and elevated ALT (53%). One patient in the AC arm died from heart failure with low EF 2 months after having a normal echo 1-3 wk after AC#4. The rate of missing echos was 14%. Of 133 completed echos, 124 (93%) were evaluable for GLS. Mean GLS was &lt;-19% at all times in the simvastatin+AC arm. Mean GLS was &lt;-19% at BL and pre-AC#2 in the AC arm, but ≥-19% at post-AC times in the AC arm. Mean EF was &gt;60% at all times in both arms. Among 27 patients evaluable for the primary endpoint, there was no significant difference in mean |Δ| in GLS from BL to 1-3 wk after AC#4 between the arms (Simvastatin+AC: 0.42%; AC: 1.11%, p=0.57). In addition, there were no differences in the mean|Δ| in GLS from BL to any other time between the arms (all p&gt;0.1). The proportion of patients with GLS&lt;-19% was higher in the simvastatin+AC arm than in the AC arm pre-AC#2 (73% vs 44%), 1-3 wk after AC#4 (67% vs 38%), 24 wk after AC #1 (53% vs 25%) and 52 wk after AC#1 (53% vs 25%) (all p&gt;0.05). The proportion of patients with RelΔ in GLS≥11% from BL was lower in the simvastatin+AC arm than in the AC arm pre-AC#2 (13% vs 19%), 1-3 wk after AC#4 (20% vs 44%) and 24 wk after AC#1(27% vs 31%) (all p&gt;0.05). Conclusion: Simvastatin did not result in a statistically significant difference in the mean |Δ| in GLS from BL to 1-3 wk after AC#4. However, the study was underpowered due to small sample size and there was a suggestion of reduced CT with simvastatin. Co-administration of simvastatin and AC was safe and serial echocardiographic strain monitoring was feasible. Further studies are needed to evaluate the cardioprotective effect of statins on strain in BC patients receiving anthracyclines.
Citation Format: Smith KL, Griffin JM, Tsai H-L, Leathers M, Hays A, Lu D-Y, Zhang Z, Rosner GL, Russell SD, Connolly RM, Jelovac D, Visvanathan K, Wolff AC, Stearns V, Abraham T. Effect of simvastatin on cardiac strain in breast cancer patients receiving anthracycline therapy [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P4-16-09.