Korean Circ J.  2013 Mar;43(3):174-181. 10.4070/kcj.2013.43.3.174.

Evaluation of Short-Term Use of N-Acetylcysteine as a Strategy for Prevention of Anthracycline-Induced Cardiomyopathy: EPOCH Trial - A Prospective Randomized Study

• Jo SH
• Kim LS
• Kim SA
• Kim HS
• Han SJ
• Park WJ
• Choi YJ

• KMID: 2224961
• DOI: http://doi.org/10.4070/kcj.2013.43.3.174

Abstract

BACKGROUND AND OBJECTIVES
We investigate to determine whether N-acetylcysteine (NAC) can prevent anthracycline-induced cardiotoxicity.
SUBJECTS AND METHODS
A total of 103 patients were enrolled in this prospective randomized open label controlled trial. They are patients first diagnosed with breast cancer or lymphoma, who require chemotherapy, including anthracycline like adriamycine or epirubicine. Patients were randomized to the NAC group {n=50; 1200 mg orally every 8 hours starting before and ending after the intravenous infusion of anthracycline in all chemotherapy cycles (3-6)} or the control group (n=53). Primary outcome was the decrease in left ventricular ejection fraction (LVEF) absolutely > or =10% from the baseline and concomitantly <50% at 6-month. Composite of all-cause death, heart failure and readmission were compared.
RESULTS
The primary outcome was not significantly different in the NAC and control groups {3/47 (6.4%) vs. 1/52 (1.9%), p=0.343}. The mean LVEF significantly decreased in both the NAC (from 64.5 to 60.8%, p=0.001) and control groups (from 64.1 to 61.3%, p<0.001) after the completion of whole chemotherapy. The mean LVEF change did not differ between the two groups (-3.64% in NAC vs. -2.78% in control group, p=0.502). Left ventricular (LV) end systolic dimension increased with higher trend in NAC by 3.08+/-4.56 mm as compared with 1.47+/-1.83 mm in the control group (p=0.064). LV end diastolic dimension did not change in each group and change does not differ in both. Peak E, A and E/A ratio change and cardiac enzymes were comparable in two groups. Cumulative 12-month event rate was 6% and 3.8% in the NAC group and the control group, respectively, with no difference (p=0.672).
CONCLUSION
We cannot prove that NAC prevents anthracycline-induced cardiomyopathy.

Keyword

Acetylcysteine; Anthracyclines; Cardiomyopathies

MeSH Terms

Acetylcysteine
Anthracyclines
Breast Neoplasms
Cardiomyopathies
Doxorubicin
Epirubicin
Heart Failure
Humans
Infusions, Intravenous
Lymphoma
Prospective Studies
Stroke Volume
Acetylcysteine
Anthracyclines
Doxorubicin
Epirubicin

Figure

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  Fig. 1 Rate of anthracycline induced cardiac toxicity define as 10% or more decrease of LVEF and concomitant EF <50% at 6-month between NAC and control group. LVEF: left ventricular ejection fraction, NAC: N-acetylcysteine.

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  Fig. 2 Cumulative event rate at 12-month between NAC and control group. NAC: N-acetylcysteine.

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