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

<h4>Background</h4>Amodiaquine 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 (electrocar...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	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
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Medicine R
Acceso en línea:	https://doaj.org/article/9f5554785c2245449964647e4dd37413
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:9f5554785c2245449964647e4dd37413
record_format	dspace
spelling	oai:doaj.org-article:9f5554785c2245449964647e4dd374132021-12-02T19:56:07ZThe cardiovascular effects of amodiaquine and structurally related antimalarials: An individual patient data meta-analysis.1549-12771549-167610.1371/journal.pmed.1003766https://doaj.org/article/9f5554785c2245449964647e4dd374132021-09-01T00:00:00Zhttps://doi.org/10.1371/journal.pmed.1003766https://doaj.org/toc/1549-1277https://doaj.org/toc/1549-1676<h4>Background</h4>Amodiaquine 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.<h4>Methods and findings</h4>Studies 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 < 0.001) and pyronaridine (-1.2 ms, -3.6 to +1.3, p < 0.001). In individuals aged ≥12 years, amodiaquine reduced heart rate (mean reduction = 15.2 beats per minute [bpm], 95% CI: 13.4 to 17.0) more than piperaquine (10.5 bpm, 7.7 to 13.3, p = 0.0013), lumefantrine (9.3 bpm, 6.4 to 12.2, p < 0.001), pyronaridine (6.6 bpm, 4.0 to 9.3, p < 0.001), and chloroquine (5.9 bpm, 3.2 to 8.5, p < 0.001) and was associated with a higher risk of potentially symptomatic sinus bradycardia (≤50 bpm) than lumefantrine (risk difference: 14.8%, 95% CI: 5.4 to 24.3, p = 0.0021) and chloroquine (risk difference: 8.0%, 95% CI: 4.0 to 12.0, p < 0.001). The effect of amodiaquine on the heart rate of children aged <12 years compared with other antimalarials was not clinically significant. Study limitations include the unavailability of individual patient-level adverse event data for most included participants, but no serious complications were documented.<h4>Conclusions</h4>While 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.Xin Hui S ChanIlsa L HaeuslerYan Naung WinJames PikeBorimas HanboonkunupakarnMaryam HanafiahSue J LeeAbdoulaye DjimdéCaterina I FanelloJean-René KiechelMarcus Vg LacerdaBernhards OgutuMarie A OnyambokoAndré M SiqueiraElizabeth A AshleyWalter Rj TaylorNicholas J WhitePublic Library of Science (PLoS)articleMedicineRENPLoS Medicine, Vol 18, Iss 9, p e1003766 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R
spellingShingle	Medicine R 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 The cardiovascular effects of amodiaquine and structurally related antimalarials: An individual patient data meta-analysis.
description	<h4>Background</h4>Amodiaquine 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.<h4>Methods and findings</h4>Studies 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 < 0.001) and pyronaridine (-1.2 ms, -3.6 to +1.3, p < 0.001). In individuals aged ≥12 years, amodiaquine reduced heart rate (mean reduction = 15.2 beats per minute [bpm], 95% CI: 13.4 to 17.0) more than piperaquine (10.5 bpm, 7.7 to 13.3, p = 0.0013), lumefantrine (9.3 bpm, 6.4 to 12.2, p < 0.001), pyronaridine (6.6 bpm, 4.0 to 9.3, p < 0.001), and chloroquine (5.9 bpm, 3.2 to 8.5, p < 0.001) and was associated with a higher risk of potentially symptomatic sinus bradycardia (≤50 bpm) than lumefantrine (risk difference: 14.8%, 95% CI: 5.4 to 24.3, p = 0.0021) and chloroquine (risk difference: 8.0%, 95% CI: 4.0 to 12.0, p < 0.001). The effect of amodiaquine on the heart rate of children aged <12 years compared with other antimalarials was not clinically significant. Study limitations include the unavailability of individual patient-level adverse event data for most included participants, but no serious complications were documented.<h4>Conclusions</h4>While 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.
format	article
author	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
author_facet	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
author_sort	Xin Hui S Chan
title	The cardiovascular effects of amodiaquine and structurally related antimalarials: An individual patient data meta-analysis.
title_short	The cardiovascular effects of amodiaquine and structurally related antimalarials: An individual patient data meta-analysis.
title_full	The cardiovascular effects of amodiaquine and structurally related antimalarials: An individual patient data meta-analysis.
title_fullStr	The cardiovascular effects of amodiaquine and structurally related antimalarials: An individual patient data meta-analysis.
title_full_unstemmed	The cardiovascular effects of amodiaquine and structurally related antimalarials: An individual patient data meta-analysis.
title_sort	cardiovascular effects of amodiaquine and structurally related antimalarials: an individual patient data meta-analysis.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/9f5554785c2245449964647e4dd37413
work_keys_str_mv	AT xinhuischan thecardiovasculareffectsofamodiaquineandstructurallyrelatedantimalarialsanindividualpatientdatametaanalysis AT ilsalhaeusler thecardiovasculareffectsofamodiaquineandstructurallyrelatedantimalarialsanindividualpatientdatametaanalysis AT yannaungwin thecardiovasculareffectsofamodiaquineandstructurallyrelatedantimalarialsanindividualpatientdatametaanalysis AT jamespike thecardiovasculareffectsofamodiaquineandstructurallyrelatedantimalarialsanindividualpatientdatametaanalysis AT borimashanboonkunupakarn thecardiovasculareffectsofamodiaquineandstructurallyrelatedantimalarialsanindividualpatientdatametaanalysis AT maryamhanafiah thecardiovasculareffectsofamodiaquineandstructurallyrelatedantimalarialsanindividualpatientdatametaanalysis AT suejlee thecardiovasculareffectsofamodiaquineandstructurallyrelatedantimalarialsanindividualpatientdatametaanalysis AT abdoulayedjimde thecardiovasculareffectsofamodiaquineandstructurallyrelatedantimalarialsanindividualpatientdatametaanalysis AT caterinaifanello thecardiovasculareffectsofamodiaquineandstructurallyrelatedantimalarialsanindividualpatientdatametaanalysis AT jeanrenekiechel thecardiovasculareffectsofamodiaquineandstructurallyrelatedantimalarialsanindividualpatientdatametaanalysis AT marcusvglacerda thecardiovasculareffectsofamodiaquineandstructurallyrelatedantimalarialsanindividualpatientdatametaanalysis AT bernhardsogutu thecardiovasculareffectsofamodiaquineandstructurallyrelatedantimalarialsanindividualpatientdatametaanalysis AT marieaonyamboko thecardiovasculareffectsofamodiaquineandstructurallyrelatedantimalarialsanindividualpatientdatametaanalysis AT andremsiqueira thecardiovasculareffectsofamodiaquineandstructurallyrelatedantimalarialsanindividualpatientdatametaanalysis AT elizabethaashley thecardiovasculareffectsofamodiaquineandstructurallyrelatedantimalarialsanindividualpatientdatametaanalysis AT walterrjtaylor thecardiovasculareffectsofamodiaquineandstructurallyrelatedantimalarialsanindividualpatientdatametaanalysis AT nicholasjwhite thecardiovasculareffectsofamodiaquineandstructurallyrelatedantimalarialsanindividualpatientdatametaanalysis AT xinhuischan cardiovasculareffectsofamodiaquineandstructurallyrelatedantimalarialsanindividualpatientdatametaanalysis AT ilsalhaeusler cardiovasculareffectsofamodiaquineandstructurallyrelatedantimalarialsanindividualpatientdatametaanalysis AT yannaungwin cardiovasculareffectsofamodiaquineandstructurallyrelatedantimalarialsanindividualpatientdatametaanalysis AT jamespike cardiovasculareffectsofamodiaquineandstructurallyrelatedantimalarialsanindividualpatientdatametaanalysis AT borimashanboonkunupakarn cardiovasculareffectsofamodiaquineandstructurallyrelatedantimalarialsanindividualpatientdatametaanalysis AT maryamhanafiah cardiovasculareffectsofamodiaquineandstructurallyrelatedantimalarialsanindividualpatientdatametaanalysis AT suejlee cardiovasculareffectsofamodiaquineandstructurallyrelatedantimalarialsanindividualpatientdatametaanalysis AT abdoulayedjimde cardiovasculareffectsofamodiaquineandstructurallyrelatedantimalarialsanindividualpatientdatametaanalysis AT caterinaifanello cardiovasculareffectsofamodiaquineandstructurallyrelatedantimalarialsanindividualpatientdatametaanalysis AT jeanrenekiechel cardiovasculareffectsofamodiaquineandstructurallyrelatedantimalarialsanindividualpatientdatametaanalysis AT marcusvglacerda cardiovasculareffectsofamodiaquineandstructurallyrelatedantimalarialsanindividualpatientdatametaanalysis AT bernhardsogutu cardiovasculareffectsofamodiaquineandstructurallyrelatedantimalarialsanindividualpatientdatametaanalysis AT marieaonyamboko cardiovasculareffectsofamodiaquineandstructurallyrelatedantimalarialsanindividualpatientdatametaanalysis AT andremsiqueira cardiovasculareffectsofamodiaquineandstructurallyrelatedantimalarialsanindividualpatientdatametaanalysis AT elizabethaashley cardiovasculareffectsofamodiaquineandstructurallyrelatedantimalarialsanindividualpatientdatametaanalysis AT walterrjtaylor cardiovasculareffectsofamodiaquineandstructurallyrelatedantimalarialsanindividualpatientdatametaanalysis AT nicholasjwhite cardiovasculareffectsofamodiaquineandstructurallyrelatedantimalarialsanindividualpatientdatametaanalysis
_version_	1718375856631447552

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

Ejemplares similares