Enalapril and Carvedilol for Preventing Chemotherapy-Induced Left Ventricular Systolic Dysfunction in Patients With Malignant Hemopathies

• Published in: Journal of the American College of Cardiology Vol. 61; no. 23; pp. 2355 - 2362
• Main Authors: Bosch, Xavier, MD, PhD, Rovira, Montserrat, MD, PhD, Sitges, Marta, MD, PhD, Domènech, Ariadna, RN, Ortiz-Pérez, José T., MD, PhD, de Caralt, Teresa M., MD, PhD, Morales-Ruiz, Manuel, PhD, Perea, Rosario J., MD, PhD, Monzó, Mariano, MD, PhD, Esteve, Jordi, MD, PhD
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 11.06.2013
• Subjects: cardiac toxicity; Cardiovascular; carvedilol; chemotherapy; enalapril; Internal Medicine; left ventricular dysfunction; prevention; SBP; enalapril; carvedilol; LVEF; CMR; left ventricular dysfunction; peripheral blood hematopoietic stem-cell transplantation; chemotherapy; systolic blood pressure; left ventricular ejection fraction; left ventricular systolic dysfunction; hematopoietic stem-cell transplantation; ARB; cardiac toxicity; PBSCT; angiotensin-converting enzyme inhibitor; angiotensin II receptor blocker; ACEI; LVSD; cardiac magnetic resonance; HSCT; prevention
• ISSN: 0735-1097; 1558-3597
• DOI: 10.1016/j.jacc.2013.02.072

Objectives This study sought to evaluate the efficacy of enalapril and carvedilol to prevent chemotherapy-induced left ventricular systolic dysfunction (LVSD) in patients with hematological malignancies. Background Current chemotherapy may induce LVSD. Angiotensin-converting enzyme inhibitors and beta-blockers prevent LVSD in animal models of anthracycline-induced cardiomyopathy. Methods In this randomized, controlled study, 90 patients with recently diagnosed acute leukemia (n = 36) or patients with malignant hemopathies undergoing autologous hematopoietic stem cell transplantation (HSCT) (n = 54) and without LVSD were randomly assigned to a group receiving enalapril and carvedilol (n = 45) or to a control group (n = 45). Echocardiographic and cardiac magnetic resonance (CMR) imaging studies were performed before and at 6 months after randomization. The primary efficacy endpoint was the absolute change from baseline in LV ejection fraction (LVEF). Results The mean age of patients was 50 ± 13 years old, and 43% were women. At 6 months, LVEF did not change in the intervention group but significantly decreased in controls, resulting in a −3.1% absolute difference by echocardiography (p = 0.035) and −3.4% (p = 0.09) in the 59 patients who underwent CMR. The corresponding absolute difference (95% confidence interval [CI]) in LVEF was −6.38% (95% CI: −11.9 to −0.9) in patients with acute leukemia and −1.0% (95% CI: −4.5 to 2.5) in patients undergoing autologous HSCT (p = 0.08 for interaction between treatment effect and disease category). 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 Combined treatment with enalapril and carvedilol may prevent LVSD in patients with malignant hemopathies treated with intensive chemotherapy. The clinical relevance of this strategy should be confirmed in larger studies. (Prevention of Left Ventricular Dysfunction During Chemotherapy [OVERCOME]; NCT01110824 )