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

by Xin Hui S. Chan, Ilsa L. Haeusler, Yan Naung Win, James Pike, Borimas Hanboonkunupakarn, Maryam Hanafiah, Sue J. Lee, Abdoulaye Djimd é, 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 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 chloro...
Source: PLoS Medicine - Category: Internal Medicine Authors: Source Type: research