Electrocardiographic study in Ghanaian children with uncomplicated malaria, treated with artesunate-amodiaquine or artemether-lumefantrine
Electrocardiographic study in Ghanaian children with uncomplicated malaria, treated with artesunate-amodiaquine or artemether-lumefantrine
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DOI：
10.1186/1475-2875-11-420
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发表时间：
2012-12-17
期刊：
影响因子：
3
通讯作者：
Goka, Bamenla Q.
中科院分区：
文献类型：
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作者：
Adjei, George O.;Oduro-Boatey, Collins;Goka, Bamenla Q.
背景：几种抗疟疾药物与心血管不良反应有关。当不同的抗疟药联合使用时，这些影响可能会加剧。有没有报告尚未对潜在的心脏效应的组合青蒿琥酯阿莫地喹。方法：心电图（ECG）的间隔在加纳儿童与单纯疟疾青蒿琥酯阿莫地喹（n=47），进行了比较与蒿甲醚-苯芴醇（n=30）治疗的儿童。治疗后1、2、3、7和28天重复ECG测量。结果：青蒿琥酯-阿莫地喹治疗前两组患者的平均心电图间期基本相似，而治疗后两组患者的平均心电图间期与阿莫地喹的主要代谢产物去乙基阿莫地喹（DEAQ）的血药浓度呈显著正相关。治疗后（第3天），所有受试者的ECG间期均较基线发生显著变化，但两个治疗组之间无差异。与蒿甲醚-本芴醇治疗组相比，青蒿琥酯-阿莫地喹治疗组发生窦性心动过缓的儿童比例显著较高（7/47 vs 0/30; chi（2）p=0.03）。发生心动过缓的受试者年龄明显较大，DEAQ浓度高于未发生心动过缓的受试者。两组间QTc间期延长的受试者比例无显著差异，未观察到QTc间期延长与DEAQ水平之间的关系。在任何subjects.Conclusion：青蒿琥酯，阿莫地喹治疗导致窦性心动过缓的发病率高于蒿甲醚-苯芴醇治疗儿童单纯疟疾，但没有临床意义的心律失常联合青蒿琥酯阿莫地喹诱导。这些研究结果虽然令人放心，但可能意味着非阿莫地喹青蒿素联合疗法可能更适合治疗那些有心脏影响风险的疟疾患者。
Background: Several anti-malarial drugs are associated with adverse cardiovascular effects. These effects may be exacerbated when different anti-malarials are used in combination. There has been no report yet on the potential cardiac effects of the combination artesunate-amodiaquine.Methods: Electrocardiographic (ECG) intervals in Ghanaian children with uncomplicated malaria treated with artesunate-amodiaquine (n=47), were compared with that of children treated with artemether-lumefantrine (n=30). The ECG measurements were repeated one, two, three, seven and 28 days after treatment. The ECG intervals of artesunate-amodiaquine treated subjects were correlated with plasma concentrations of desethylamodiaquine (DEAQ), the main metabolite of amodiaquine.Results: The mean ECG intervals were similar in both groups before treatment. After treatment (day 3), ECG intervals changed significantly from baseline in all subjects, but there were no differences between the two treatment groups. A significantly higher proportion of children treated with artesunate-amodiaquine developed sinus bradycardia compared with artemether-lumefantrine treated subjects (7/47 vs 0/30; chi(2) p=0.03). Subjects who developed bradycardia were significantly older, and had higher DEAQ concentrations than those who did not develop bradycardia. The proportion of subjects with QTc interval prolongations did not differ significantly between the groups, and no relationship between prolonged QTc intervals and DEAQ levels were observed. No clinically significant rhythm disturbances were observed in any of the subjects.Conclusion: Artesunate-amodiaquine treatment resulted in a higher incidence of sinus bradycardia than artemether-lumefantrine treatment in children with uncomplicated malaria, but no clinically significant rhythm disturbances were induced by combining artesunate with amodiaquine. These findings, although reassuring, may imply that non-amodiaquine based artemisinin combination therapy may be preferable for malaria treatment in patients who are otherwise at risk of cardiac effects.