Chloroquine, but not hydroxychlorquine, prolongs the QT interval in a primary care population
MSc Jonas L Isaksen, MD, PhD b , Anders G Holst, MD d Adrian Pietersen, MD, PhD Jonas B Nielsen, MSc, PhD Claus Graff, MD Jørgen K Kanters
doi:10.1101/2020.06.19.20135475
Background-Chloroquine (CQ) and Hydroxychloroquine (HCQ) have recently been suggested as treatment for the current Corona Virus Disease 2019 (COVID-19) pandemic. However, despite their long-term use and only few case reports on adverse effects, CQ and HCQ are listed as a known risk of the lethal ventricular arrhythmia Torsade de Pointes and their cardiac safety profile is being questioned. Thus, we aimed to investigate the electrocardiographic and mortality effects of CQ and HCQ in a primary care population. Methods-We used Danish health care registers and electrocardiograms (ECGs) from primary care to define three studies. 1) A paired study of subjects with ECGs before and during use of CQ/HCQ, 2) a matched ECG study of subjects taking CQ/HCQ compared to controls, and 3) a mortality study on people taking HCQ matched to control. In both matched studies, we adjusted for connective tissue diseases, use of QT-prolonging drugs, and cardiac disease. We used the QTc interval as the marker for electrocardiographic safety. In the mortality study, cases were followed from first claimed prescription until 300 days after estimated completion of the last prescription. 95% confidence intervals follow estimates in parenthesis. Results-Use of CQ was associated with a 5.5 (0.7;10) ms increase in QTc in the paired study (n=10). In the matched study (n=28, controls=280), QTc was insignificantly increased in subjects taking CQ by 4.7 (-3.4;13) ms. With a ΔQTc of 1.0 (-5.6;7.5), use of HCQ was not associated with an increased QTc in the paired study (n=32). In the matched study (n=172, controls=1,720), QTc also was not different between groups (p=0.5). In the mortality study (n=3,368), use of HCQ was associated with a hazard ratio of 0.67 (0.43;1.05). Conclusions-In subjects free of COVID-19, we found a small increase in QTc associated with use of chloroquine, but not hydroxychloroquine. We found no increased mortality associated with use of hydroxychloroquine. is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
References
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'abstract': '<jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>Chloroquine '
'(CQ) and Hydroxychloroquine (HCQ) have recently been suggested as treatment for the current '
'Corona Virus Disease 2019 (COVID-19) pandemic. However, despite their long-term use and only '
'few case reports on adverse effects, CQ and HCQ are listed as a known risk of the lethal '
'ventricular arrhythmia Torsade de Pointes and their cardiac safety profile is being '
'questioned. Thus, we aimed to investigate the electrocardiographic and mortality effects of '
'CQ and HCQ in a primary care '
'population.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>We used '
'Danish health care registers and electrocardiograms (ECGs) from primary care to define three '
'studies. 1) A paired study of subjects with ECGs before and during use of CQ/HCQ, 2) a '
'matched ECG study of subjects taking CQ/HCQ compared to controls, and 3) a mortality study on '
'people taking HCQ matched to control. In both matched studies, we adjusted for connective '
'tissue diseases, use of QT-prolonging drugs, and cardiac disease. We used the QTc interval as '
'the marker for electrocardiographic safety. In the mortality study, cases were followed from '
'first claimed prescription until 300 days after estimated completion of the last '
'prescription. 95% confidence intervals follow estimates in '
'parenthesis.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Use of CQ '
'was associated with a 5.5 (0.7;10) ms increase in QTc in the paired study (n=10). In the '
'matched study (n=28, controls=280), QTc was insignificantly increased in subjects taking CQ '
'by 4.7 (−3.4;13) ms. With a ΔQTc of 1.0 (−5.6;7.5), use of HCQ was not associated with an '
'increased QTc in the paired study (n=32). In the matched study (n=172, controls=1,720), QTc '
'also was not different between groups (p=0.5). In the mortality study (n=3,368), use of HCQ '
'was associated with a hazard ratio of 0.67 '
'(0.43;1.05).</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>In '
'subjects free of COVID-19, we found a small increase in QTc associated with use of '
'chloroquine, but not hydroxychloroquine. We found no increased mortality associated with use '
'of hydroxychloroquine.</jats:p></jats:sec>',
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