دورية أكاديمية
أعرض في EDS

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

التفاصيل البيبلوغرافية
العنوان: The cardiovascular effects of amodiaquine and structurally related antimalarials: An individual patient data meta-analysis.
المؤلفون: Chan XHS; Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.; Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom., Haeusler IL; University College London Great Ormond Street Institute of Child Health, London, United Kingdom., Win YN; Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.; Health and Diseases Control Unit, Naypyidaw, Myanmar., Pike J; Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand., Hanboonkunupakarn B; Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.; Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok Thailand., Hanafiah M; Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand., Lee SJ; Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.; Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom., Djimdé A; Malaria Research and Training Center, Department of Epidemiology of Parasitic Diseases, Faculty of Pharmacy, University of Science Techniques and Technologies of Bamako, Bamako, Mali., Fanello CI; Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.; Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom., Kiechel JR; Drug for Neglected Diseases Initiative, Geneva, Switzerland., Lacerda MV; Fundação de Medicina Tropical Dr Heitor Vieira Dourado, Manaus, Brazil.; Instituto Leônidas e Maria Deane (FIOCRUZ-Amazonas), Fundacão Oswaldo Cruz, Manaus, Brazil., Ogutu B; Kenya Medical Research Institute, Kisumu, Kenya., Onyamboko MA; Kinshasa School of Public Health, University of Kinshasa, Kinshasa, Democratic Republic of Congo., Siqueira AM; Instituto Leônidas e Maria Deane (FIOCRUZ-Amazonas), Fundacão Oswaldo Cruz, Manaus, Brazil.; Instituto Nacional de Infectologia Evandro Chagas, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil., Ashley EA; Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.; Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom., Taylor WR; Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.; Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom., White NJ; Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.; Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.
المصدر: PLoS medicine [PLoS Med] 2021 Sep 07; Vol. 18 (9), pp. e1003766. Date of Electronic Publication: 2021 Sep 07 (Print Publication: 2021).
نوع المنشور: Journal Article; Meta-Analysis; Research Support, Non-U.S. Gov't; Systematic Review
اللغة: English
بيانات الدورية: Publisher: Public Library of Science Country of Publication: United States NLM ID: 101231360 Publication Model: eCollection Cited Medium: Internet ISSN: 1549-1676 (Electronic) Linking ISSN: 15491277 NLM ISO Abbreviation: PLoS Med Subsets: MEDLINE
أسماء مطبوعة: Original Publication: San Francisco, CA : Public Library of Science, [2004]-
مواضيع طبية MeSH: Amodiaquine/*adverse effects , Antimalarials/*adverse effects , Bradycardia/*chemically induced , Heart Conduction System/*drug effects , Heart Rate/*drug effects , Long QT Syndrome/*chemically induced, Adolescent ; Adult ; Bradycardia/diagnosis ; Bradycardia/physiopathology ; Cardiotoxicity ; Child ; Child, Preschool ; Female ; Heart Conduction System/physiopathology ; Humans ; Infant ; Long QT Syndrome/diagnosis ; Long QT Syndrome/physiopathology ; Male ; Middle Aged ; Randomized Controlled Trials as Topic ; Risk Assessment ; Risk Factors ; Young Adult
مستخلص: 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.
Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: EAA and NJW are members of the Editorial Board of PLOS Medicine.
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معلومات مُعتمدة: United Kingdom WT_ Wellcome Trust; MR/N013468/1 United Kingdom MRC_ Medical Research Council; 107886/Z/15/Z United Kingdom WT_ Wellcome Trust; 106698/Z/14/Z United Kingdom WT_ Wellcome Trust
المشرفين على المادة: 0 (Antimalarials)
220236ED28 (Amodiaquine)
تواريخ الأحداث: Date Created: 20210907 Date Completed: 20211130 Latest Revision: 20240815
رمز التحديث: 20240815
مُعرف محوري في PubMed: PMC8454971
DOI: 10.1371/journal.pmed.1003766
PMID: 34492005
قاعدة البيانات: MEDLINE
الوصف
تدمد:1549-1676
DOI:10.1371/journal.pmed.1003766