Efficacy of Treatment With Carvedilol in Preventing Early-Stage Left Ventricular Dysfunction in Patients With Breast Cancer Candidated to Receive Trastuzumab Using 2D Speckle-Tracking Echocardiography

Background: Treatment-induced cardiotoxicity is one of the major side effects of trastuzumab treatment in patients with breast cancer. Left ventricular (LV) dysfunction is the leading cause of treatment-induced cardiotoxicity. The development of treatment-induced cardiotoxicity during cancer treatment may force patients to modify or quit the treatment. In this trial, we evaluated the prophylactic effects of carvedilol on LV dysfunction in patients with breast cancer receiving trastuzumab using 2D speckle-tracking echocardiography (2DSTE). Methods: We conducted an open-label randomized clinical trial and enrolled 71 non-metastatic HER-2 positive patients with breast cancer candidated to receive trastuzumab. Carvedilol was administered concomitantly with the trastuzumab standard regimen at a dosage of 6.25 mg twice a day and up-titrated to the maximum tolerated dosage. The 2DSTE parameters to evaluate the LV systolic and diastolic functions were evaluated initially and 3 months thereafter. Results: Thirty-six patients were randomly assigned to the carvedilol group and 35 patients to the control group. The mean left ventricular ejection fraction (LVEF) was not significantly different either in both groups or between the 2 groups (P=.61) during the follow-up. In contrast, the global longitudinal strain of the LV (GLS) (P=.000) and the strain rate of the LV systolic function (SRS) (P=.004) as markers of the LV systolic function were reduced in the control group. Furthermore, the LV strain rate of the early (SRE) and late (SRA) diastolic functions were preserved in the patients who received prophylactic carvedilol (P=.000 and P=.005, respectively). Conclusions: Concomitant carvedilol treatment with a maximum tolerable dose in patients with nonmetastatic HER2-positive breast cancer under treatment with trastuzumab might be effective on the reduction of systolic and diastolic echocardiographic findings other than the LVEF in patients with weak markers of heart failure.