Role of ACE inhibitors in anthracycline-induced cardiotoxicity: A randomized, double-blind, placebo-controlled trial.

Abstract

Several measures including drugs have been tried to reduce anthracycline cardiotoxicity. The lack of randomized trials prompted this study to assess the role of an angiotensin converting enzyme (ACE) inhibitor (enalapril) in anthracycline-induced cardiotoxicity in children with hematological malignancies. A randomized, double-blind, placebo-controlled trial was conducted on 84 patients with leukemia (41) and lymphoma (43) who received anthracyclines (doxorubicin and/or daunorubicin) at cumulative dose ≥200mg/m2 . The patients were randomized to receive either enalapril [group A (n=44)] or placebo [group B (n=40)] for 6months. Left ventricular ejection fraction (LVEF) and cardiac biomarkers (cardiac troponin I [cTnI], probrain natriuretic peptide [proBNP], and creatine kinase MB [CK-MB]) were assessed at baseline and 6months. The primary outcome was a measured decrease in LVEF (≥20%). Secondary outcome measures were changes in cardiac biomarkers and the development of heart failure or arrhythmias. LVEF decreased in both groups at 6months, more so in group B (62.25±5.49vs 56.15±4.79, P<0.001). A ≥20% decrease was seen in 3 patients in group B but none in group A (P=0.21). Cardiac biomarkers increased more in group B at 6months, and the increase was significant for proBNP (49.60±35.97vs 98.60±54.24, P<0.001) and cTnI (0.01±0.00vs 0.011±0.003, P=0.035) but not significant for CK-MB (1.08±0.18vs 1.21±0.44, P=0.079). In group A, 9.1% of the patients showed an increase in proBNP level ≥100 compared with 37.5% in group B (P<0.001). No patient developed heart failure or arrhythmia. Enalapril has a role in reducing cardiac toxicity after anthracycline administration.