Cardioprotective Effects of Carvedilol in Inhibiting Doxorubicin-induced Cardiotoxicity.

PURPOSE: Anthracyclines (ANTs) are a class of active antineoplastic agents with topoisomerase-interacting activity that are considered the most active agents for the treatment of breast cancer. We investigated the efficacy of carvedilol in the inhibition of ANT-induced cardiotoxicity.

METHODS: In this randomized, single-blind, placebo-controlled study, 91 women with recently diagnosed breast cancer undergoing ANT therapy were randomly assigned to groups treated with either carvedilol (n = 46) or placebo (n = 45). Echocardiography was performed before and at 6 months after randomization, and absolute changes in the mean left ventricular ejection fraction, left ventricular end diastolic volume, and left ventricular end systolic volume were determined. Furthermore, the percentage change in the left atrial (LA) diameter and other variables of left ventricular (LV) diastolic function, such as transmitral Doppler parameters, including early (E wave) and late (A wave) diastolic velocities, E/A ratio and E wave deceleration time, pulmonary venous Doppler signals, including forward systolic (S wave) and diastolic (D wave) velocities into LA, late diastolic atrial reversal velocity, and early diastolic tissue Doppler mitral annular velocity (e') were measured. In addition, tissue Doppler mitral annular systolic (s') velocity, as a marker of early stage of LV systolic dysfunction, E/e' ratio, as a determinant of LV filling pressure, and troponin I level, as a marker of myocardial necrosis were measured.

RESULTS: At the end of follow-up period, left ventricular ejection fraction did not change in the carvedilol group. However, this parameter was significantly reduced in the control group (P < 0.001). Echocardiography showed that both left ventricular end systolic volume and LA diameter were significantly increased compared with the baseline measures in the control group. In pulse Doppler studies, pulmonary venous peak atrial reversal flow velocity was significantly increased in the control group. Moreover, a significant decrease in the mitral annuli early diastolic (e') and peak systolic (s') velocities and a significant increase in the E (the peak early diastolic velocity)/e' ratio in the control group were also observed. However, none of these variables were adversely changed at the end of follow-up in the carvedilol group. Furthermore, the TnI level was significantly higher in the control group than in the carvedilol group (P = 0.036) at 30 days after the initiation of chemotherapy.

CONCLUSIONS: Prophylactic use of carvedilol may inhibit the development of anthracycline-induced cardiotoxicity, even at low doses.