Hydroxychloroquine plus azithromycin increases heart risk, finds global
study

Date:
August 25, 2020
Source:
Columbia University Irving Medical Center
Summary:
In the largest observational study of hydroxychloroquine and
azithromycin, the drug combination has been linked to significant
cardiovascular risks, including death.



FULL STORY ==========================================================================
The combination of hydroxychloroquine (HCQ) and azithromycin (AZM) has
been linked to significant cardiovascular risks, including mortality, in
the largest safety study ever performed on both HCQ and HCQ+AZM. This
network study, led by the Observational Health Data Sciences and
Informatics community, was recently published in Lancet Rheumatology.


========================================================================== OHDSI has established an international network of researchers and
observational health databases with a central coordinating center housed
at the Department of Biomedical Informatics at Columbia University.

In patients with rheumatoid arthritis, HCQ treatment in the short term
(30 days) was found to not carry excess risk of complications associated
with its use, but HCQ treatment in the long term had a 65% relative
increase in cardiovascular-related mortality, compared to sulfasalazine.

HCQ + AZM had a cardiovascular mortality risk that was more than twice
(2.19) as high as the comparative treatment even in the short term based
on findings from more than 320,000 users of that combination therapy. This treatment also produced a 15-20% increased rate of angina/chest pain
and heart failure.

This study, first published on MedRxiv, has already made significant
impacts in the healthcare community. On April 23, the European Medicines
Agency (EMA) cited the study in a warning about the risk of serious
side effects with chloroquine and hydroxychloroquine. In July, the
EMA again highlighted the study, among other efforts within the OHDSI community, in its eighth revision of The European Network of Centres
for Pharmacoepidemiology and Pharmacovigilance (ENCePP) Guide on
Methodological Standards in Pharmacoepidemiology.

This is the first published study to be generated from the OHDSI COVID
Study-a- thon, a global effort in March to set the foundation for OHDSI
efforts to design and execute network observational studies around characterization, patient-level prediction and population-level effect estimation to inform decision-making around the global pandemic. Multiple studies, several of which are highlighted later, have been posted to
MedRxiv and are currently under peer review.

HCQ, a drug commonly used in the treatment of malaria, lupus and
rheumatoid arthritis (RA), gained early attention during the pandemic
as a potential COVID-19 treatment. The short-term (<30 days) safety
profile did not identify excess risk in any of 16 severe adverse events
as compared to a similar RA drug, sulfasalazine (SSZ). Long-term HCQ
therapy was associated with a 65% increase in cardiovascular mortality
as compared to SSZ.

"Hydroxychloroquine, both alone and in combination with azithromycin,
gained strong consideration as a potential COVID treatment without
a large-scale study of its overall safety profile," said Daniel Prieto-Alhambra, PhD, co-senior author on this study. "We had
access to an unprecedented amount of data on this drug, and we were
relieved to find no worrying side effects in the short-term use
of hydroxychloroquine. However, when prescribed in combination with azithromycin, it may induce heart failure and cardiovascular mortality and
we would urge caution in using the two together." This study examined
more than 950,000 HCQ users through deidentified electronic health
records and administrative claims data over a 20-year period. Records
were collected from 14 different databases spanning six nations (Germany, Japan, Netherlands, Spain, United Kingdom, United States) and then mapped
to the OMOP Common Data Model to generate this large-scale analysis.

"At medical school we were taught to 'first do no harm' and to me,
our study focuses on this core belief of modern medicine," said
Jennifer Lane, MD, who served as co-lead author on this study along
with Jamie Weaver. "OHDSI has the power to investigate this question in
a very thorough way and to go through rigorous steps. We are looking at patients from the general population, which is why it is so important to
look at data from multiple countries. There are reasons why you may get
bias from one data source, but if we find a signal in the Netherlands,
and we find it in Spain, and we find it in the U.S., then we know we
have something." The study was developed and executed by the OHDSI (Observational Health Data Sciences and Informatics) community, a multi-stakeholder, interdisciplinary collaborative to bring out the
value of health data through large-scale analytics. All solutions are open-source, and links to the study protocol, code and results are posted
at the bottom of this release.

"It required a global effort to generate this level of reproducible,
reliable real-world evidence to inform decision-making around COVID
treatment," said Patrick Ryan, PhD, co-senior author on this study. "Our community collaborated for years to develop the high-level analytics which
set the course for these studies. Standardizing data for nearly 1,000,000 patients on hydroxychloroquine provides confidence in these findings,
and we are pleased to see that this study has already helped make a
positive clinical impact as treatment options continue to be evaluated."

========================================================================== Story Source: Materials provided by
Columbia_University_Irving_Medical_Center. Note: Content may be edited
for style and length.


========================================================================== Journal Reference:
1. Jennifer C E Lane, James Weaver, Kristin Kostka, Talita
Duarte-Salles,
Maria Tereza F Abrahao, Heba Alghoul, Osaid Alser, Thamir M
Alshammari, Patricia Biedermann, Juan M Banda, Edward Burn, Paula
Casajust, Mitchell M Conover, Aedin C Culhane, Alexander Davydov,
Scott L DuVall, Dmitry Dymshyts, Sergio Fernandez-Bertolin,
Kristina Fister, Jill Hardin, Laura Hester, George Hripcsak,
Benjamin Skov Kaas-Hansen, Seamus Kent, Sajan Khosla, Spyros
Kolovos, Christophe G Lambert, Johan van der Lei, Kristine E
Lynch, Rupa Makadia, Andrea V Margulis, Michael E Matheny, Paras
Mehta, Daniel R Morales, Henry Morgan-Stewart, Mees Mosseveld,
Danielle Newby, Fredrik Nyberg, Anna Ostropolets, Rae Woong Park,
Albert Prats-Uribe, Gowtham A Rao, Christian Reich, Jenna Reps,
Peter Rijnbeek, Selva Muthu Kumaran Sathappan, Martijn Schuemie,
Sarah Seager, Anthony G Sena, Azza Shoaibi, Matthew Spotnitz,
Marc A Suchard, Carmen O Torre, David Vizcaya, Haini Wen, Marcel
de Wilde, Junqing Xie, Seng Chan You, Lin Zhang, Oleg Zhuk,
Patrick Ryan, Daniel Prieto-Alhambra. Risk of hydroxychloroquine
alone and in combination with azithromycin in the treatment of
rheumatoid arthritis: a multinational, retrospective study. The
Lancet Rheumatology, 2020; DOI: 10.1016/S2665-9913(20)30276-9 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/08/200825135245.htm

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