The cardiovascular effects of amodiaquine and structurally related antimalarials: An individual patient data meta-analysis
| Autor(a) principal: | |
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| Data de Publicação: | 2021 |
| Outros Autores: | , , , , , , , , , , , , , , , |
| Tipo de documento: | Artigo |
| Idioma: | eng |
| Título da fonte: | Repositório Institucional da FIOCRUZ (ARCA) |
| Texto Completo: | https://www.arca.fiocruz.br/handle/icict/50182 |
Resumo: | Mahidol University. Faculty of Tropical Medicine. Mahidol-Oxford Tropical Medicine Research Unit. Bangkok, Thailand / University of Oxford. Nuffield Department of Medicine. Centre for Tropical Medicine and Global Health. Oxford, United Kingdom. |
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Chan, Xin Hui S.Haeusler, Ilsa L.Win, Yan NaungPike, JamesHanboonkunupakarn, BorimasHanafiah, MaryamLee, Sue J.Djimdé, AbdoulayeFanello, Caterina I.Kiechel, Jean-RenéLacerda, Marcus V. G.Ogutu, BernhardsOnyamboko, Marie A.Siqueira, André M.Ashley, Elizabeth A.Taylor, Walter R. J.White, Nicholas J.2021-12-06T15:16:50Z2021-12-06T15:16:50Z2021CHAN, Xin Hui S. et al. The cardiovascular effects of amodiaquine and structurally related antimalarials: An individual patient data meta-analysis. PLoS medicine, v. 18, n. 9, p. 1-25, 2021.1549-1277https://www.arca.fiocruz.br/handle/icict/5018210.1371/journal.pmed.1003766engPublic Library of ScienceThe cardiovascular effects of amodiaquine and structurally related antimalarials: An individual patient data meta-analysisinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleMahidol University. Faculty of Tropical Medicine. Mahidol-Oxford Tropical Medicine Research Unit. Bangkok, Thailand / University of Oxford. Nuffield Department of Medicine. Centre for Tropical Medicine and Global Health. Oxford, United Kingdom.University College London Great Ormond Street Institute of Child Health. London, United Kingdom.Mahidol University. Faculty of Tropical Medicine. Mahidol-Oxford Tropical Medicine Research Unit. Bangkok, Thailand / Health and Diseases Control Unit. Naypyidaw, Myanmar.Mahidol University. Faculty of Tropical Medicine. Mahidol-Oxford Tropical Medicine Research Unit. Bangkok, Thailand.Mahidol University. Faculty of Tropical Medicine. Mahidol-Oxford Tropical Medicine Research Unit. Bangkok, Thailand / Mahidol University. Faculty of Tropical Medicine. Department of Clinical Tropical Medicine. Bangkok, Thailand.Mahidol University. Faculty of Tropical Medicine. Mahidol-Oxford Tropical Medicine Research Unit. Bangkok, Thailand.Mahidol University. Faculty of Tropical Medicine. Mahidol-Oxford Tropical Medicine Research Unit. Bangkok, Thailand / University of Oxford. Nuffield Department of Medicine. Centre for Tropical Medicine and Global Health. Oxford, United Kingdom.University of Science Techniques and Technologies of Bamako. Faculty of Pharmacy. Department of Epidemiology of Parasitic Diseases. Malaria Research and Training Center. Bamako, Mali.Mahidol University. Faculty of Tropical Medicine. Mahidol-Oxford Tropical Medicine Research Unit. Bangkok, Thailand / University of Oxford. Nuffield Department of Medicine. Centre for Tropical Medicine and Global Health. Oxford, United Kingdom.Drug for Neglected Diseases Initiative. Geneva, Switzerland.Fundação Oswaldo Cruz. Instituto Leônidas e Maria Deane. Manaus, AM, Brasil / Fundação de Medicina Tropical Dr. Heitor Vieira Dourado. Manaus, AM, Brasil.Kenya Medical Research Institute. Kisumu, Kenya.University of Kinshasa. Kinshasa School of Public Health. Kinshasa, Democratic Republic of Congo.Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Instituto Leônidas e Maria Deane. Manaus, AM, Brasil.Mahidol University. Faculty of Tropical Medicine. Mahidol-Oxford Tropical Medicine Research Unit. Bangkok, Thailand / University of Oxford. Nuffield Department of Medicine. Centre for Tropical Medicine and Global Health. Oxford, United Kingdom.Mahidol University. Faculty of Tropical Medicine. Mahidol-Oxford Tropical Medicine Research Unit. Bangkok, Thailand / University of Oxford. Nuffield Department of Medicine. Centre for Tropical Medicine and Global Health. Oxford, United Kingdom.Mahidol University. Faculty of Tropical Medicine. Mahidol-Oxford Tropical Medicine Research Unit. Bangkok, Thailand / University of Oxford. Nuffield Department of Medicine. Centre for Tropical Medicine and Global Health. Oxford, United Kingdom.Background: 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. Methods and findings: 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. Conclusions: 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.Heart rateAntimalarialsAmodiaquineMalariaChloroquineElectrocardiographyBradycardiaBody temperatureinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-83099https://www.arca.fiocruz.br/bitstream/icict/50182/1/license.txt586c046dcfeef936e32f0323bb9a47c0MD51ORIGINALThe cardiovascular_Andre_Siqueira_etal_INI_2021.pdfThe cardiovascular_Andre_Siqueira_etal_INI_2021.pdfapplication/pdf3237440https://www.arca.fiocruz.br/bitstream/icict/50182/2/The%20cardiovascular_Andre_Siqueira_etal_INI_2021.pdfefdad2bac5e5d1e58ce95516dac609ceMD52icict/501822021-12-06 12:16:50.792oai:www.arca.fiocruz.br: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ório 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| dc.title.pt_BR.fl_str_mv |
The cardiovascular effects of amodiaquine and structurally related antimalarials: An individual patient data meta-analysis |
| title |
The cardiovascular effects of amodiaquine and structurally related antimalarials: An individual patient data meta-analysis |
| spellingShingle |
The cardiovascular effects of amodiaquine and structurally related antimalarials: An individual patient data meta-analysis Chan, Xin Hui S. Heart rate Antimalarials Amodiaquine Malaria Chloroquine Electrocardiography Bradycardia Body temperature |
| 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 |
The cardiovascular effects of amodiaquine and structurally related antimalarials: An individual patient data meta-analysis |
| author |
Chan, Xin Hui S. |
| author_facet |
Chan, Xin Hui S. Haeusler, Ilsa L. Win, Yan Naung Pike, James Hanboonkunupakarn, Borimas Hanafiah, Maryam Lee, Sue J. Djimdé, Abdoulaye Fanello, Caterina I. Kiechel, Jean-René Lacerda, Marcus V. G. Ogutu, Bernhards Onyamboko, Marie A. Siqueira, André M. Ashley, Elizabeth A. Taylor, Walter R. J. White, Nicholas J. |
| author_role |
author |
| author2 |
Haeusler, Ilsa L. Win, Yan Naung Pike, James Hanboonkunupakarn, Borimas Hanafiah, Maryam Lee, Sue J. Djimdé, Abdoulaye Fanello, Caterina I. Kiechel, Jean-René Lacerda, Marcus V. G. Ogutu, Bernhards Onyamboko, Marie A. Siqueira, André M. Ashley, Elizabeth A. Taylor, Walter R. J. White, Nicholas J. |
| author2_role |
author author author author author author author author author author author author author author author author |
| dc.contributor.author.fl_str_mv |
Chan, Xin Hui S. Haeusler, Ilsa L. Win, Yan Naung Pike, James Hanboonkunupakarn, Borimas Hanafiah, Maryam Lee, Sue J. Djimdé, Abdoulaye Fanello, Caterina I. Kiechel, Jean-René Lacerda, Marcus V. G. Ogutu, Bernhards Onyamboko, Marie A. Siqueira, André M. Ashley, Elizabeth A. Taylor, Walter R. J. White, Nicholas J. |
| dc.subject.en.pt_BR.fl_str_mv |
Heart rate Antimalarials Amodiaquine Malaria Chloroquine Electrocardiography Bradycardia Body temperature |
| topic |
Heart rate Antimalarials Amodiaquine Malaria Chloroquine Electrocardiography Bradycardia Body temperature |
| description |
Mahidol University. Faculty of Tropical Medicine. Mahidol-Oxford Tropical Medicine Research Unit. Bangkok, Thailand / University of Oxford. Nuffield Department of Medicine. Centre for Tropical Medicine and Global Health. Oxford, United Kingdom. |
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2021 |
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2021-12-06T15:16:50Z |
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2021-12-06T15:16:50Z |
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2021 |
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info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/article |
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CHAN, Xin Hui S. et al. The cardiovascular effects of amodiaquine and structurally related antimalarials: An individual patient data meta-analysis. PLoS medicine, v. 18, n. 9, p. 1-25, 2021. |
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https://www.arca.fiocruz.br/handle/icict/50182 |
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1549-1277 |
| dc.identifier.doi.none.fl_str_mv |
10.1371/journal.pmed.1003766 |
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CHAN, Xin Hui S. et al. The cardiovascular effects of amodiaquine and structurally related antimalarials: An individual patient data meta-analysis. PLoS medicine, v. 18, n. 9, p. 1-25, 2021. 1549-1277 10.1371/journal.pmed.1003766 |
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Public Library of Science |
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