Evaluation of the effects on the QT-interval of 4 artemisinin-based combination therapies with a correction-free and heart rate-free method.

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  • Additional Information
    • Source:
      Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101563288 Publication Model: Electronic Cited Medium: Internet ISSN: 2045-2322 (Electronic) Linking ISSN: 20452322 NLM ISO Abbreviation: Sci Rep Subsets: MEDLINE
    • Publication Information:
      Original Publication: London : Nature Publishing Group, copyright 2011-
    • Subject Terms:
      Antimalarials/*adverse effects ; Artemisinins/*pharmacology ; Heart Rate/*drug effects; Adolescent ; Amodiaquine ; Antimalarials/pharmacology ; Arrhythmias, Cardiac ; Artemether ; Artemether, Lumefantrine Drug Combination ; Child ; Child, Preschool ; Drug Combinations ; Ethanolamines/pharmacology ; Female ; Fluorenes/therapeutic use ; Humans ; Long QT Syndrome/drug therapy ; Malaria/drug therapy ; Malaria, Falciparum/drug therapy ; Male ; Quinolines ; Young Adult
    • Abstract:
      Several antimalarial drugs are known to prolong ventricular repolarization as evidenced by QT/QTc interval prolongation. This can lead to Torsades de Pointes, a potentially lethal ventricular arrhythmia. Whether this is the case with artemisinin-based combination therapies (ACTs) remains uncertain. Assessment of the extent of QTc prolongation with antimalarials is hampered by important variations of heart rate during malaria crises and previous studies have reported highly variable values of QTc prolongations with ACTs. We assessed QTc prolongation with four ACTs, using high quality ECG recording and measurement techniques, during the first episode of malaria in 2,091 African patients enrolled in the WANECAM study which also monitored clinical safety. Using an original and robust method of QTc assessment, independent from heart rate changes and from the method of QT correction, we were able to accurately assess the extent of mean maximum QTc prolongation with the four ACTs tested. There was no evidence of proarrhythmia with any treatment during the study although dihydroartemisinin-piperaquine, artesunate-amodiaquine and artemether-lumefantrine significantly prolonged QTc. The extent of prolongation of ventricular repolarization can be accurately assessed in studies where heart rate changes impede QTc assessment.
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    • Accession Number:
      0 (Antimalarials)
      0 (Artemether, Lumefantrine Drug Combination)
      0 (Artemisinins)
      0 (Drug Combinations)
      0 (Ethanolamines)
      0 (Fluorenes)
      0 (Quinolines)
      0 (amodiaquine, artesunate drug combination)
      220236ED28 (Amodiaquine)
      6A9O50735X (artenimol)
      9RMU91N5K2 (artemisinin)
      A0HV2Q956Y (piperaquine)
      C7D6T3H22J (Artemether)
    • Publication Date:
      Date Created: 20190131 Date Completed: 20200828 Latest Revision: 20231005
    • Publication Date:
      20231005
    • Accession Number:
      PMC6351684
    • Accession Number:
      10.1038/s41598-018-37113-5
    • Accession Number:
      30696921