Effect of artemisinin-piperaquine treatment on the electrocardiogram of malaria patients

Wu, Wanting; Liang, Yuan; Wu, Guangchao; Su, Yinghang; Zhang, Hongying; Zhang, Zhenyan; Deng, Changsheng; Wang, Qi; Huang, Bo; Tan, Bo; Zhou, Chongjun; Song, Jianping

doi:10.1590/0037-8682-0453-2018

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Short Communication • Rev. Soc. Bras. Med. Trop. 52 • 2019 • https://doi.org/10.1590/0037-8682-0453-2018 linkcopy

Effect of artemisinin-piperaquine treatment on the electrocardiogram of malaria patients

Authorship SCIMAGO INSTITUTIONS RANKINGS

INTRODUCTION: Concern regarding the cardiotoxicity of antimalarials has been renewed because of their potential to cause QT/QTc interval prolongation related to torsade de pointes (TdP). Artemisinin-piperaquine (AP) is considered an effective artemisinin-based combination therapy (ACT) for malaria.

METHODS: This study involved a retrospective analysis of clinical data of 93 hospitalized malaria patients who had received AP orally. Electrocardiograms (ECGs) were obtained at specific time points in the original study.

RESULTS: Some cases of QT prolongation were observed. However, no TdP was found.

CONCLUSIONS: AP may cause QT interval prolongation in some malaria patients but may not lead to TdP.

Keywords:
ECG; QT; Artemisinin-piperaquine; Malaria; Cambodia

Characteristics	Frequency (n = 93)	Percentage (%)
Gender
Male	69	74.2
Female	24	25.8
Age (years)
≤20	46	49.5
21-30	18	19.4
31-40	16	17.2
41-50	11	11.8
>50	2	2.2
Symptoms
Fever	91	97.8
Headaches	93	100
Body aches	38	40.9
Malaise	80	86.0
Vomiting	41	44.1
Dyspnea	3	3.2
Convulsions	1	1.1
Diminished consciousness	1	1.1
Other*	22	23.7
Characteristics	Mean	SD
Weight (kg)	46.02	12.59
Body temperature (°C)	38.24	1.19
Fever recovery time (h)	28.27	19.05
Plasmodium removal time (h)	72.98	39.53
QTcF-Before (ms)	389.67	24.83
QTcF-4h-1^st dose (ms)	383.08	26.28
QTcF-4h-2^nd dose (ms)	383.30	24.09
QTcB-Before (ms)	421.21	31.93
QTcB-4h-1^st dose (ms)	401.54	32.56
QTcB-4h-2^nd dose (ms)	396.70	29.78
Characteristics	4h-1 ^st dose	4h-2 ^nd dose
Maximum QTcF prolongation (ms)	58.61	72.18
Maximum QTcB prolongation (ms)	63.36	74.81
QTcF prolongation	38(41.30%)	37(40.22%)
QTcF shortening	54 (58.70%)	55 (59.78%)
QTcB prolongation	24 (26.09%)	21(22.83%)
QTcB shortening	67(72.83%)	71(77.17%)
ΔQTcF > 30 ms	8(8.70%)	12(13.04%)
ΔQTcF > 60 ms	0	1(1.09%)
ΔQTcB > 30 ms	4(4.35%)	3(3.26%)
ΔQTcB > 60 ms	1(1.09%)	3(3.26%)

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Sociedade Brasileira de Medicina Tropical - SBMT Sociedade Brasileira de Medicina Tropical - SBMT, Núcleo de Medicina Tropical UnB, Sala 43C 70904-970, E-mails: rsbmt@sbmt.org.br | artes.rsbmt@gmail.com , WhatsApp: SBMT (61) 9.9192-6496, WhatsApp: RSBMT (34) 3317-5855 - Brasília - DF - Brazil
E-mail: rsbmt@sbmt.org.br

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[TFN1] *mild cough, 1 case; palpitation, 4 cases; nausea, 11 cases; abdominal pain, 5 cases; dizziness, 5 cases; diarrhea, 3 cases. Fever recovery time refers to the time from the start of treatment to the return of body temperature to normal (≤37.3 °C). Seventy-five patients had a fever. The 18 patients who did not have a fever were excluded from this index. Plasmodium removal time refers to the time from the start of treatment to the observation of negative blood smears. All patients had positive smears at enrollment, and blood smears for 81 patients were observed to be negative during hospitalization. The other 12 patients reverted to negative smears at follow-up, so the removal time of these patients could not be accurately calculated. Abbreviations: 4h-1^st dose, 4 hours after the first dose; 4h-2^nd dose, 4 hours after the second dose. ΔQTc was defined as the difference in QTc before and 4 hours after each medication. ΔQTc >30 ms was defined as moderate prolongation, and that >60 ms was defined as severe prolongation.