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Published:May 22, 2020DOI:https://doi.org/10.1016/S0140-6736(20)31180-6
Hydroxychloroquine or chloroquine, often in combination with a second-generation macrolide, are being widely used for treatment of COVID-19, despite no conclusive evidence of their benefit.
Although generally safe when used for approved indications such as autoimmune disease or malaria, the safety and benefit of these treatment regimens are poorly evaluated in COVID-19.
We did a multinational registry analysis of the use of hydroxychloroquine or chloroquine with or without a macrolide for treatment of COVID-19. The registry comprised data from 671 hospitals in six continents. We included patients hospitalised between Dec 20, 2019, and April 14, 2020, with a positive laboratory finding for SARS-CoV-2. Patients who received one of the treatments of interest within 48 h of diagnosis were included in one of four treatment groups (chloroquine alone, chloroquine with a macrolide, hydroxychloroquine alone, or hydroxychloroquine with a macrolide), and patients who received none of these treatments formed the control group. Patients for whom one of the treatments of interest was initiated more than 48 h after diagnosis or while they were on mechanical ventilation, as well as patients who received remdesivir, were excluded. The main outcomes of interest were in-hospital mortality and the occurrence of de-novo ventricular arrhythmias (non-sustained or sustained ventricular tachycardia or ventricular fibrillation).
96 032 patients (mean age 53·8 years, 46·3% women) with COVID-19 were hospitalised during the study period and met the inclusion criteria. Of these, 14 888 patients were in the treatment groups (1868 received chloroquine, 3783 received chloroquine with a macrolide, 3016 received hydroxychloroquine, and 6221 received hydroxychloroquine with a macrolide) and 81 144 patients were in the control group. 10 698 (11·1%) patients died in hospital. After controlling for multiple confounding factors (age, sex, race or ethnicity, body-mass index, underlying cardiovascular disease and its risk factors, diabetes, underlying lung disease, smoking, immunosuppressed condition, and baseline disease severity), when compared with mortality in the control group (9·3%), hydroxychloroquine (18·0%; hazard ratio 1·335, 95% CI 1·223–1·457), hydroxychloroquine with a macrolide (23·8%; 1·447, 1·368–1·531), chloroquine (16·4%; 1·365, 1·218–1·531), and chloroquine with a macrolide (22·2%; 1·368, 1·273–1·469) were each independently associated with an increased risk of in-hospital mortality. Compared with the control group (0·3%), hydroxychloroquine (6·1%; 2·369, 1·935–2·900), hydroxychloroquine with a macrolide (8·1%; 5·106, 4·106–5·983), chloroquine (4·3%; 3·561, 2·760–4·596), and chloroquine with a macrolide (6·5%; 4·011, 3·344–4·812) were independently associated with an increased risk of de-novo ventricular arrhythmia during hospitalisation.
We were unable to confirm a benefit of hydroxychloroquine or chloroquine, when used alone or with a macrolide, on in-hospital outcomes for COVID-19. Each of these drug regimens was associated with decreased in-hospital survival and an increased frequency of ventricular arrhythmias when used for treatment of COVID-19.
William Harvey Distinguished Chair in Advanced Cardiovascular Medicine at Brigham and Women's Hospital.
The absence of an effective treatment against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has led clinicians to redirect drugs that are known to be effective for other medical conditions to the treatment of COVID-19. Key among these repurposed therapeutic agents are the antimalarial drug chloroquine and its analogue hydroxychloroquine, which is used for the treatment of autoimmune diseases, such as systemic lupus erythematosus and rheumatoid arthritis.1, 2 These drugs have been shown in laboratory conditions to have antiviral properties as well as immunomodulatory effects.3, 4 However, the use of this class of drugs for COVID-19 is based on a small number of anecdotal experiences that have shown variable responses in uncontrolled observational analyses, and small, open-label, randomised trials that have largely been inconclusive.5, 6 The combination of hydroxychloroquine with a second-generation macrolide, such as azithromycin (or clarithromycin), has also been advocated, despite limited evidence for its effectiveness.7 Previous studies have shown that treatment with chloroquine, hydroxychloroquine, or either drug combined with a macrolide can have the cardiovascular adverse effect of prolongation of the QT interval, which could be a mechanism that predisposes to ventricular arrhythmias.8, 9
Art. 1: « Le Grand Orient de Belgique, obédience masculine, maillon de la franc-maçonnerie universelle, demande à celui qui se présente à l’Initiation d’être honnête homme et d’être capable de comprendre et de propager les principes maçonniques. Il exige de ses membres, la sincérité des convictions, le désir de s’instruire et le dévouement. Il forme une société d’hommes probes et libres qui, liés par des sentiments de liberté, d’égalité et de fraternité, travaillent individuellement et en commun au progrès social, et exercent ainsi la bienveillance dans le sens le plus étendu ».
« La pensée ne doit jamais se soumettre, ni à un dogme, ni à un parti, ni à une passion, ni à un intérêt, ni à une idée préconçue, ni à quoi que ce soit, si ce n'est aux faits eux-mêmes, parce que, pour elle, se soumettre, ce serait cesser d'être. » Henri Poincaré
« Que puis-je savoir ? - Que dois-je faire ? - Que m'est-il permis d'espérer ? » Emmanuel Kant