Key result
Combined treatment with enalapril and carvedilol prevented chemotherapy-induced LVSD at 6 months, with a -3.1% absolute difference in LVEF compared to controls (p=0.035).
Why the study?
Current chemotherapy may induce left ventricular systolic dysfunction, but angiotensin-converting enzyme inhibitors and beta-blockers prevent it in animal models of anthracycline-induced cardiomyopathy.
RCT (n=90)
randomly assigned
Mean Difference: -3.1
p-value: p=0.035
Captured external expert commentary on this paper, strongest first. Original sources are linked where available.
“The OVERCOME study has shown that concomitant treatment with enalapril and carvedilol may prevent LVSD in patients with malignant hemopathies treated with high-dose chemotherapy regimens. The results were consistent as measured with two-dimensional echocardiography or CMR, although the lower number of patients studied with the latter method precluded obtaining a conventional significant statistical difference.”
“These prior publications suggest that anthracycline-induced direct myocardial injury is not mediated by the renin-angiotensin-aldosterone system (RAAS). Instead, RAAS activation is hypothesized to occur only after myocardial injury occurrence, playing a role in the myocardial remodeling process following subclinical injury.”
May support cardioprotection during chemotherapy; hypothesis-generating and requires randomized confirmation before practice change.
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).
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Bosch et al. (2013) conducted an RCT in malignant hemopathies (n=90). enalapril and carvedilol vs. control group was evaluated on absolute change from baseline in LV ejection fraction (LVEF) (MD -3.1%, p=0.035). Combined treatment with enalapril and carvedilol prevented chemotherapy-induced LVSD at 6 months, with a -3.1% absolute difference in LVEF compared to controls (p=0.035).
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