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Vol. 73. Issue 8.
Pages 693-694 (August 2020)
Letter to the Editor
DOI: 10.1016/j.rec.2020.05.016
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Living evidence in response to controversies about the use of antimalarials in COVID-19
Evidencia viva como respuesta a las controversias en el uso de antimaláricos en COVID-19
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Azucena Santillán-Garcíaa,
Corresponding author
ebevidencia@gmail.com

Corresponding author:
, Rocío Bravo-Jeriab, Francisca Verdugo-Paivab,c, Gabriel Radab,c,d
a Servicio de Cardiología, Hospital Universitario de Burgos, Burgos, Spain
b Centro Evidencia UC, Centro Asociado Cochrane Chile, Pontificia Universidad Católica de Chile, Santiago, Chile
c Fundación Epistemonikos, Santiago, Chile
d Departamento de Medicina Interna, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
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To the Editor,

The health crisis resulting from the SARS-CoV-2 pandemic has created an area of considerable clinical uncertainty. More answers are needed than the scientific knowledge is able to generate at its usual rate. Currently, we find that there are few completed primary studies on COVID-19, and the preliminary data that have been published provide low evidence levels. Faced with this uncertain situation, the most appropriate thing to do is interpret the available evidence with caution and avoid making precipitate decisions that could be more harmful than beneficial.1

In cardiology, several controversial subjects have emerged, such as treatment with angiotensin-converting enzyme inhibitors and angiotensin-receptor blockers used in COVID-192 as well as the open debate on chloroquine and hydroxychloroquine that, alone or in combination with antibiotics such as azithromycin and antivirals, are being used to treat the disease.

The boom in these antimalarial drugs in the management of COVID-19 originated in a scientific meeting in China, in the middle of February 2020, attended by the country's clinical trial authors, government authorities, and representatives from regulatory agencies. During that meeting it was concluded that chloroquine had strong activity against COVID-19 and it was recommended to include it in the guidelines for prevention, diagnosis and treatment of pneumonia caused by COVID-19, issued by the National Health Commission of the People's Republic of China.3

Another key moment in the propagation of this idea was when on 19 March a nonrandomized French study, which supported the Chinese hypothesis, was made public.4 This study was widely shared by unconventional media such as WhatsApp, even before it appeared in the scientific databases. Despite the serious methodological limitations of this study, within hours the message had left its mark. Even the president of the USA stated on the 21 of March on his Twitter account that “Hydroxychloroquine & azithromycin, taken together, have a real chance to be one of the biggest game changers in the history of medicine.”5

In light of this enthusiasm, the cardiovascular effects of these drugs have been reviewed, and it has been found that, although the incidence of cardiac events is low, they may produce adverse effects such as hypotension or tachycardia (mainly with intravenous administration), QT prolongation (greater with concomitant azithromycin treatment), and interactions with amiodarone, digoxin, and beta-blockers. Clinical recommendations are being issued that advise against concomitant use with amiodarone and suggest monitoring digoxin and QT interval in patients taking hydroxychloroquine and azithromycin.6

However, the production of scientific literature regarding COVID-19 is increasing at an incredible, dramatic rate and new publications are appearing rapidly. It is therefore essential that clinicians have tools available that ensure good quality scientific evidence that is updated almost in real time. One such tool is Living Systematic Reviews, in which systematic reviews are conducted leaving open a review window that allows the incorporation of new evidence as it is published and may even result in changes in the recommendations based on emergent data. These are extremely useful and pertinent to the current situation.

There is already a live repository of scientific evidence on the effectiveness of antimalarials against coronavirus infection that currently includes, among many other things, 20 systematic reviews, 4 clinical trials that report results and 115 registered ongoing randomized trials. This facilitates rapid, effective decision-making with the best and most up-to-date data available.7

The COVID-19 pandemic has forced us to adapt our health care and has also shown us that scientific information must be available to clinicians when they need it, which requires an immediate capacity to respond. Meeting this challenge is essential not only for the efficacy of treatments but also for their safety. Live evidence is in the running to be one of great assets of evidence-based practice of our time.

CONFLICTS OF INTEREST

G. Rada and F. Verdugo-Paiva have links with Epistemonikos and the L·OVE database for systematic reviews. All authors are members of the COVID-19 LOVE Working Group.

.

References
[1]
J.P.A. Ioannidis.
Coronavirus disease 2019: the harms of exaggerated information and non-evidence-based measures.
Eur J Clin Invest., (2020),
[2]
F. Soria Arcos, A. Romero-Puche, T. Vicente Vera.
Controversias sobre el tratamiento con IECA/ARA-II y COVID-19.
Rev Esp Cardiol., 73 (2020), pp. 516
[3]
J. Gao, Z. Tian, X. Yang.
Breakthrough: Chloroquine phosphate has shown apparent efficacy in treatment of COVID-19 associated pneumonia in clinical studies.
Biosci Trends., 14 (2020), pp. 72-73
[4]
P. Gautret, J. Lagier, P. Parola, et al.
Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial.
Int J Antimicrob Agents., (2020),
[5]
Twitter. Donald Trump (@realDonaldTrump), 21 mar 2020. Available at: https://twitter.com/realDonaldTrump/status/1241367239900778501. Accessed 4 May 2020.
[6]
E.J. Zaidel, F.S. Wyss Quintana, A. Sosa Liprandi, et al.
Hidroxicloroquina. Mensajes desde la cardiología en tiempos de pandemia por coronavirus. Medicina (Buenos Aires), (2020), pp. 80
[7]
Fundación Epistemonikos. L OVE Platform. Antimalarials for Coronavirus infection. Available at: https://app.iloveevidence.com/loves/5e6fdb9669c00e4ac072701d?question_domain=5b1dcd8ae611de7ae84e8f14&population=5e6fdab269c00e4ac072701c∫ervention=5d168392daeedf730326b7ce. Accessed 4 May 2020.
Copyright © 2020. Sociedad Española de Cardiología
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