PLoS Medicine (Sep 2021)

The cardiovascular effects of amodiaquine and structurally related antimalarials: An individual patient data meta-analysis.

  • Xin Hui S Chan,
  • Ilsa L Haeusler,
  • Yan Naung Win,
  • James Pike,
  • Borimas Hanboonkunupakarn,
  • Maryam Hanafiah,
  • Sue J Lee,
  • Abdoulaye Djimdé,
  • Caterina I Fanello,
  • Jean-René Kiechel,
  • Marcus Vg Lacerda,
  • Bernhards Ogutu,
  • Marie A Onyamboko,
  • André M Siqueira,
  • Elizabeth A Ashley,
  • Walter Rj Taylor,
  • Nicholas J White

DOI
https://doi.org/10.1371/journal.pmed.1003766
Journal volume & issue
Vol. 18, no. 9
p. e1003766

Abstract

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BackgroundAmodiaquine is a 4-aminoquinoline antimalarial similar to chloroquine that is used extensively for the treatment and prevention of malaria. Data on the cardiovascular effects of amodiaquine are scarce, although transient effects on cardiac electrophysiology (electrocardiographic QT interval prolongation and sinus bradycardia) have been observed. We conducted an individual patient data meta-analysis to characterise the cardiovascular effects of amodiaquine and thereby support development of risk minimisation measures to improve the safety of this important antimalarial.Methods and findingsStudies of amodiaquine for the treatment or prevention of malaria were identified from a systematic review. Heart rates and QT intervals with study-specific heart rate correction (QTcS) were compared within studies and individual patient data pooled for multivariable linear mixed effects regression. The meta-analysis included 2,681 patients from 4 randomised controlled trials evaluating artemisinin-based combination therapies (ACTs) containing amodiaquine (n = 725), lumefantrine (n = 499), piperaquine (n = 716), and pyronaridine (n = 566), as well as monotherapy with chloroquine (n = 175) for uncomplicated malaria. Amodiaquine prolonged QTcS (mean = 16.9 ms, 95% CI: 15.0 to 18.8) less than chloroquine (21.9 ms, 18.3 to 25.6, p = 0.0069) and piperaquine (19.2 ms, 15.8 to 20.5, p = 0.0495), but more than lumefantrine (5.6 ms, 2.9 to 8.2, p ConclusionsWhile caution is advised in the use of amodiaquine in patients aged ≥12 years with concomitant use of heart rate-reducing medications, serious cardiac conduction disorders, or risk factors for torsade de pointes, there have been no serious cardiovascular events reported after amodiaquine in widespread use over 7 decades. Amodiaquine and structurally related antimalarials in the World Health Organization (WHO)-recommended dose regimens alone or in ACTs are safe for the treatment and prevention of malaria.