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Enalapril and Carvedilol for Preventing Chemotherapy-Induced Left Ventricular Systolic Dysfunction in Patients With Malignant Hemopathies. The OVERCOME Trial
Study Questions:
What is the efficacy of enalapril and carvedilol to prevent chemotherapy-induced left ventricular systolic dysfunction (LVSD) in patients with hematological malignancies?
Methods:
In this randomized, controlled study, 90 patients recently diagnosed of 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 receive enalapril and carvedilol (n = 45) or to a control group (n = 45). Echocardiographic and cardiac magnetic resonance (CMR) imaging studies were performed before and 6 months after randomization. The primary efficacy endpoint was the absolute change from baseline in LV ejection fraction (EF).
Results:
The mean age of patients was 50 ± 13 years, and 43% were woman. 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 that underwent CMR. The corresponding absolute difference (95% confidence interval) in LVEF was -6.38% (-11.9 to -0.9) in patients with acute leukemia and -1.0% (-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:
The authors concluded that combined treatment with enalapril and carvedilol may prevent LVSD in patients with malignant hemopathies treated with intensive chemotherapy.
Perspective:
This pilot study suggests that the concomitant treatment with enalapril and carvedilol may prevent LVSD in patients with malignant hemopathies treated with high-dose chemotherapy regimens. In addition, clinical events were less frequent in patients treated with the cardioprotective drugs. The study findings may have important clinical implications since millions of patients with cancer are treated with chemotherapy worldwide annually, but the benefits demonstrated in this pilot study need to be confirmed in larger prospective placebo-controlled studies.
Keywords: Ventricular Dysfunction, Carbazoles, Heart Failure, Propanolamines, Echocardiography
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