Electrocardiographic effect of artemisinin-piperaquine, dihydroartemisinin-piperaquine, and artemether-lumefantrine treatment in falciparum malaria patients

Abstract

Introduction: Artemisinin-based combination therapy (ACT), such as artemisinin-piperaquine (AP), dihydroartemisinin-piperaquine (DP), and artemether-lumefantrine (AL), is the first-line treatment for malaria in many malaria-endemic areas. However, we lack a detailed evaluation of the cardiotoxicity of these ACTs. This study aimed to analyze the electrocardiographic effects of these three ACTs in malaria patients. Methods: We analyzed the clinical data of 89 hospitalized patients with falciparum malaria who had received oral doses of three different ACTs. According to the ACTs administered, these patients were divided into three treatment groups: 27 treated with AP (Artequick), 31 with DP (Artekin), and 31 with AL (Coartem). Electrocardiograms and other indicators were recorded before and after the treatment. The QT interval was calculated using Fridericia's formula (QTcF) and Bazett's formula (QTcB). Results: Both QTcF and QTcB interval prolongation occurred in all three groups. The incidence of such prolongation between the three groups was not significantly different. The incidence of both moderate and severe prolongation was not significantly different between the three groups. The ΔQTcF and ΔQTcB of the three groups were not significantly different. The intra-group comparison showed significant prolongation of QTcF after AL treatment. Conclusions: Clinically recommended doses of DP, AL, and AP may cause QT prolongation in some malaria patients but do not cause torsades de pointes ventricular tachycardia or other arrhythmias.

Prolongation of QT Interval as a Result of Combination Therapy of Oral Artemether-Lumefantrine: A Cross-Sectional Study

“…Those ECGs showed that all three regimens had a mild effect on the QT interval. Therefore, they concluded that prolongation of QT interval is seen in all the regimens of malaria, however, this cannot lead to arrhythmias [10].…”

Solidification of Self-Emulsifying Drug Delivery Systems as a Novel Approach to the Management of Uncomplicated Malaria

“…Concurrently, more than 80 countries have applied these treatment regimens where most populations have used them for more than a decade already. Moreover, in 2007, in Côte d'Ivoire, the National Malaria Control Programme (NMCP) undertook to assure provision and distribution of ACTs in all malaria treatment centres throughout this state [24][25][26][27][28]. The reasoning behind the use of ACTs is that it is based on the simultaneous rapid elimination of asexual parasitemia, together with the alteration of the sexual stages of gametophytes, subsequently reducing malaria infectivity [29][30][31].…”

Randomized, placebo‐controlled, double‐blind phase I trial of co‐administered pyronaridine and piperaquine in healthy adults of sub‐Saharan origin

“…Because of a clinically relevant food effect that increases systemic exposure, PQP should be administered in a fasted state to mitigate QTcF prolongation 27,28 . PQP‐induced QTcF prolongation does not appear to translate into an increased risk for torsade de pointes if taken in the fasted state when other QT prolongation risk factors are controlled 29–31 . Conversely, no clinically concerning QTcF prolongation is expected with PYR and there is no clinically relevant food effect with PYR administration 29 .…”

“… 27 , 28 PQP‐induced QTcF prolongation does not appear to translate into an increased risk for torsade de pointes if taken in the fasted state when other QT prolongation risk factors are controlled. 29 , 30 , 31 Conversely, no clinically concerning QTcF prolongation is expected with PYR and there is no clinically relevant food effect with PYR administration. 29 Overall, there are no prohibitive overlaps in the PYR and PQP safety/tolerability profiles preventing further evaluation of this combination for malaria chemoprevention.…”