CECCY: LVEF Not Improved With Carvedilol During Doxorubicin Therapy
Carvedilol had no effect on left ventricular function in breast cancer patients treated with doxorubicin, but did result in a significant reduction in troponin I levels and diastolic dysfunction, according to results of the CECCY trial presented by Monica Avila, MD, on Sunday, March 11 in a Late-Breaking Clinical Trial session at ACC.18 in Orlando, FL. It was simultaneously published in the Journal of the American College of Cardiology.
Conducted in Brazil, the double-blind CECCY trial evaluated the effectiveness of carvedilol for prevention of chemotherapy-induced cardiomyopathy in female patients diagnosed with breast cancer and referred for chemotherapy including doxorubicin. A total of 96 patients were randomly assigned to carvedilol and 96 to placebo. Study drug administration began on the first day of chemotherapy.
Results showed that the primary endpoint – prevention of a ≥10 percent reduction from baseline in left ventricular ejection fraction (LVEF) after six months of treatment – was achieved in 14.5 percent of the carvedilol group and 13.5 percent of the placebo group. At six months, the mean LVEF was 63.9 percent in both groups, a nonsignificant reduction of 0.9 percent and 1.3 percent in the carvedilol and placebo groups, respectively.
Assessment of the secondary endpoints showed that significantly fewer patients in the carvedilol group than the placebo group had an increase in troponin I levels >0.04 ng/mL (26.0 vs. 41.6 percent). A significantly lower incidence of diastolic dysfunction was observed with carvedilol than with placebo. A trend toward a less pronounced increase in LV end-diastolic diameter was noted in the carvedilol group versus placebo (44.1 vs. 44.9 mm). There was no difference in BNP levels between the groups during follow-up. No differences were found in clinical adverse events between the groups.
The incidence of early onset cardiotoxicity was lower than expected for moderate to high doses of doxorubicin. Avila suggested that the discordance between increased troponin and unchanged LVEF might be due to the mild troponin elevation or that differences might appear with longer follow-up.
"This small trial was underpowered for its primary endpoint. Yet, the troponin and diastolic function results argue for possible benefit. A much larger study will be needed to tease this out," says Kim A. Eagle, MD, MACC, editor-in-chief of ACC.org.
Keywords: ACC18, ACC Annual Scientific Session, Heart Failure, Cardiotoxicity, Troponin I, Incidence, Double-Blind Method, Stroke Volume, Intention to Treat Analysis, Propanolamines, Carbazoles, Anthracyclines, Ventricular Function, Left, Breast Neoplasms, Biomarkers, Pharmacological
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