Enalapril and carvedilol for preventing chemotherapy-induced left ventricular systolic dysfunction in patients with malignant hemopathies. The OVERCOME trial (preventiOn of left Ventricular dysfunction with Enalapril and caRvedilol in patients submitted to intensive ChemOtherapy for the treatment of Malignant hEmopathies)

Abstract

Background: Cardiotoxicity is an important and a common complication of cancer chemotherapeutic drugs. It may not only be associated with significant morbidity and mortality but also often becomes a limiting factor in adequate anti-cancer treatment. Several pharmacological agents are being evaluated for their efficacy in preventing cardiotoxicity of the cancer drugs. Material and methods: Ninety patients with hematological malignancies undergoing chemotherapy and/or autologous hematopoietic stem cell transplantation (HSCT) were recruited in this study and were randomized to receive a combination of enalapril and cardvedilol (intervention arm) or no intervention (control arm). Comprehensive echocardiography and cardiac magnetic resonance imaging (MRI) were performed at baseline and at 6 months after randomization. The primary efficacy endpoint was the absolute change from baseline in left ventricular ejection fraction (LVEF). Results: The mean age of the study subjects was 50 ± 13 years. By the end of the 6 months, there was a significant fall in LVEF in controls (3.28% absolute reduction from baseline) but no change was seen in the intervention group. As a result, at 6 months, LVEF was significantly lower in the control group in comparison to the intervention group (an absolute difference of 3.1% by echocardiography and 3.4% by cardiac MRI, p = 0.035 and 0.09, respectively). The beneficial effect was seen almost exclusively in patients receiving chemotherapy alone (absolute difference in LVEF of 6.38% at 6 months, p = 0.025) and not in those undergoing HSCT (absolute difference of 1.01%, p = 0.56). In addition, compared to controls, patients in the intervention group had a lower incidence of the combined event of death or heart failure (6.7% vs. 22%, p = 0.036) and of death, heart failure, or a final LVEF <45% (6.7% vs. 24.4%, p = 0.02). Conclusions: The present trial showed that a combination of enalapril and carvedilol might prevent cardiotoxicity in patients undergoing chemotherapy for hematological malignancies.