Statins in Early Anthracycline Cardiotoxicity

Abstract

Background. Anthracycline-induced reactive oxygen species lead to oxidative stress, DNA damage, and apoptosis. Small Ras homolog (Rho) GTPases are major factors in DNA damage response. Statins are anti-inflammatory and anti-oxidative drugs and inhibitors of small Rho GTPases. Studies have suggested that the right ventricle (RV) may be more vulnerable to injury from anthracyclines. TAPSE/PAPs index measured on echocardiography strongly correlates with invasive assessment of right ventricular-pulmonary artery (RV-PA) coupling and may detect early RV dysfunction. Until now, there has been no research on the pharmacological effects of RV-PA coupling.

Objectives. Investigate the effect of rosuvastatin on cardiotoxicity in patients with breast cancer receiving a standard anthracycline-based regimen using RV-PA coupling dynamics assessed with TAPSE/PAPs index.

Methods. 226 consecutive breast cancer patients (mean age 52 ±10) with low HFA/ICOS risk were examined before and after anthracycline therapy (median cumulative dose of 250 mg/m²). Clinical assessment included Nt-pro-BNP and echocardiography at least four times: baseline, after cycle 6, and at 3 and 12 months post-treatment. After cycle 6, 28 asymptomatic patients with decreased TAPSE/PAPs index (<0.40 mmHg) and elevated Nt-pro-BNP (median 225) were identified. EF remained normal. Patients were randomized 1:1 to ACI and beta-blockers (statin−, n=14) or ACI + beta-blockers + rosuvastatin 20 mg (statin+, n=14) for 12 months.

Results. RV-PA coupling was higher in the statin+ group by trend. Statin therapy improved RV function, mitral regurgitation, and Nt-pro-BNP after 12 months.

Conclusion. A decrease in TAPSE/PAPs may signal early anthracycline cardiotoxicity. Rosuvastatin increases RV-PA coupling and improves RV function.