加纳儿童罹患无并发症疟疾，接受青蒿琥酯-阿莫地喹或青蒿琥酯-甲氟喹治疗的心电图研究。
Electrocardiographic study in Ghanaian children with uncomplicated malaria, treated with artesunate-amodiaquine or artemether-lumefantrine.
机构信息
Centre for Tropical Clinical Pharmacology & Therapeutics, University of Ghana Medical School, College of Health Sciences, University of Ghana, Accra, Ghana.
出版信息
Malar J. 2012 Dec 17;11:420. doi: 10.1186/1475-2875-11-420.
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; χ² 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.
背景
一些抗疟药物与不良心血管效应相关。当不同的抗疟药物联合使用时，这些效应可能会加剧。目前还没有关于青蒿琥酯-阿莫地喹联合用药潜在心脏效应的报告。
方法
加纳患有无并发症疟疾的儿童在接受青蒿琥酯-阿莫地喹（n=47）治疗后，其心电图（ECG）间期与接受青蒿琥酯-甲氟喹（n=30）治疗的儿童进行比较。在治疗后 1、2、3、7 和 28 天重复进行 ECG 测量。青蒿琥酯-阿莫地喹治疗组的 ECG 间隔与阿莫地喹的主要代谢物去乙基阿莫地喹（DEAQ）的血浆浓度相关。
结果
两组患者在治疗前的平均 ECG 间隔相似。治疗后（第 3 天），所有患者的 ECG 间隔均与基线相比发生显著变化，但两组之间无差异。与接受青蒿琥酯-甲氟喹治疗的患者相比，接受青蒿琥酯-阿莫地喹治疗的儿童中窦性心动过缓的比例显著更高（7/47 比 0/30；χ² p=0.03）。发生心动过缓的患者年龄明显较大，且去乙基阿莫地喹浓度明显高于未发生心动过缓的患者。两组间 QTc 间期延长的患者比例无显著差异，也未观察到 QTc 间期延长与去乙基阿莫地喹水平之间的关系。在任何患者中均未观察到临床显著的节律紊乱。
结论
与青蒿琥酯-甲氟喹治疗相比，青蒿琥酯-阿莫地喹治疗导致患有无并发症疟疾的儿童窦性心动过缓的发生率更高，但青蒿琥酯与阿莫地喹联合使用并未引起临床显著的节律紊乱。这些发现虽然令人安心，但可能意味着在其他方面存在心脏效应风险的患者中，基于非阿莫地喹的青蒿素联合疗法可能更适合疟疾治疗。
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