title: Electrocardiographic study in Ghanaian children with uncomplicated malaria, treated with artesunate-amodiaquine or artemether-lumefantrine.
abstract: BACKGROUND
  Several anti-malarial drugs are associated with adverse cardiovascular effects. These effects may be exacerbated when different anti-malarials are used in combination. There has been no report yet on the potential cardiac effects of the combination artesunate-amodiaquine.
  
  
  METHODS
  Electrocardiographic (ECG) intervals in Ghanaian children with uncomplicated malaria treated with artesunate-amodiaquine (n=47), were compared with that of children treated with artemether-lumefantrine (n=30). The ECG measurements were repeated one, two, three, seven and 28 days after treatment. The ECG intervals of artesunate-amodiaquine treated subjects were correlated with plasma concentrations of desethylamodiaquine (DEAQ), the main metabolite of amodiaquine.
  
  
  RESULTS
  The mean ECG intervals were similar in both groups before treatment. After treatment (day 3), ECG intervals changed significantly from baseline in all subjects, but there were no differences between the two treatment groups. A significantly higher proportion of children treated with artesunate-amodiaquine developed sinus bradycardia compared with artemether-lumefantrine treated subjects (7/47 vs 0/30; χ² p=0.03). Subjects who developed bradycardia were significantly older, and had higher DEAQ concentrations than those who did not develop bradycardia. The proportion of subjects with QTc interval prolongations did not differ significantly between the groups, and no relationship between prolonged QTc intervals and DEAQ levels were observed. No clinically significant rhythm disturbances were observed in any of the subjects.
  
  
  CONCLUSIONS
  Artesunate-amodiaquine treatment resulted in a higher incidence of sinus bradycardia than artemether-lumefantrine treatment in children with uncomplicated malaria, but no clinically significant rhythm disturbances were induced by combining artesunate with amodiaquine. These findings, although reassuring, may imply that non-amodiaquine based artemisinin combination therapy may be preferable for malaria treatment in patients who are otherwise at risk of cardiac effects.
authors.affiliation: Centre for Tropical Clinical Pharmacology & Therapeutics, University of Ghana Medical School, College of Health Sciences, University of Ghana, Accra, Ghana. goadjei@yahoo.com
authors.forename: George O
authors.initials: GO
authors.lastname: Adjei
authors.forename: Collins
authors.initials: C
authors.lastname: Oduro-Boatey
authors.forename: Onike P
authors.initials: OP
authors.lastname: Rodrigues
authors.forename: Lotte C
authors.initials: LC
authors.lastname: Hoegberg
authors.forename: Michael
authors.initials: M
authors.lastname: Alifrangis
authors.forename: Jorgen A
authors.initials: JA
authors.lastname: Kurtzhals
authors.forename: Bamenla Q
authors.initials: BQ
authors.lastname: Goka
mesh_terms: D000293:Adolescent; D000655:Amodiaquine / Q000008:administration & dosage / Q000009:adverse effects* / Q000031:analogs & derivatives / Q000097:blood; D000962:Antimalarials / Q000008:administration & dosage / Q000009:adverse effects*; D000077611:Artemether, Lumefantrine Drug Combination; D037621:Artemisinins / Q000008:administration & dosage / Q000009:adverse effects*; D001919:Bradycardia / Q000097:blood / Q000139:chemically induced / Q000175:diagnosis; D002648:Child; D002675:Child, Preschool; D004338:Drug Combinations; D004562:Electrocardiography; D004983:Ethanolamines / Q000008:administration & dosage / Q000009:adverse effects*; D005260:Female; D005449:Fluorenes / Q000008:administration & dosage / Q000009:adverse effects*; D005869:Ghana; D006801:Humans; D007223:Infant; D008288:Malaria / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology*; D008297:Male; D012307:Risk Factors
chemical_list: D000962:Antimalarials; D000077611:Artemether, Lumefantrine Drug Combination; D037621:Artemisinins; D004338:Drug Combinations; D004983:Ethanolamines; D005449:Fluorenes; C515299:amodiaquine, artesunate drug combination; D000655:Amodiaquine; C047386:desethylamodiaquine