Blood-pressure drugs are in the crosshairs of COVID-19 research
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[April 23, 2020]
By Deborah J. Nelson
(Reuters) - Scientists are baffled by how
the coronavirus attacks the body - killing many patients while barely
affecting others.
But some are tantalized by a clue: A disproportionate number of patients
hospitalized by COVID-19, the disease caused by the virus, have high
blood pressure. Theories about why the condition makes them more
vulnerable – and what patients should do about it – have sparked a
fierce debate among scientists over the impact of widely prescribed
blood-pressure drugs.
Researchers agree that the life-saving drugs affect the same pathways
that the novel coronavirus takes to enter the lungs and heart. They
differ on whether those drugs open the door to the virus or protect
against it. Resolving that question has taken on new urgency after an
April 8 report by the U.S. Centers for Disease Control and Prevention
showed that 72% of hospitalized COVID-19 patients 65 or older had
hypertension.
The drugs are known as ACE inhibitors and ARBs, broad categories that
include Vasotec, Valsartan, Irbesartan, as well as their generic
versions. In a recent interview with a medical journal, Anthony Fauci -
the U.S. government’s top infectious disease expert - cited a report
showing similarly high rates of hypertension among COVID-19 patients who
died in Italy and suggested the medicines, rather than the underlying
condition, may act as an accelerant for the virus.
Efforts to understand how the virus uses the pathway to the heart and
lungs, and the role of the medicines, are complicated by a lack of
rigorous studies.
“There are millions of Americans that take an ACE inhibitor or AR
daily,” said Dr Caleb Alexander, co-director of the Johns Hopkins Center
for Drug Safety and Effectiveness in Baltimore. “This is one of the most
important clinical questions.”
An estimated 100 million U.S. residents suffer from high blood pressure,
which increases the risk of heart disease, stroke and kidney failure.
About four-fifths of them need to take prescription drugs to control it,
according to the CDC. ACE inhibitors and ARBs are widely prescribed to
patients with congestive heart failure, diabetes or kidney disease. The
drugs account for billions of dollars in prescription sales worldwide.
![](http://archives.lincolndailynews.com/2020/Apr/23/images/ads/current/graue_sda_2016.png)
The absence of clear answers on how the drugs impact COVID-19 patients
has sparked rampant speculation in correspondence and editorials posted
on medical journal websites and those where scientists share unreviewed,
pre-publication study drafts.
Many patients are agonizing over whether their medicines will help or
hurt them. Doris Kertzner, 88, of Redding, Conn., said she has carefully
followed experts’ guidelines for preventing infection and keeps her
distance from others in her retirement community. Now she has a new
worry: She takes losartan, an ARB, and can’t decide whether to stop.
Dropping the medicine “presents its own problems” in dealing with her
high blood pressure.
“It’s gotten very complicated,” she said.
Dr Carlos M. Ferrario - a researcher at the Wake Forest University
School of Medicine and co-author of widely cited studies on ACE
inhibitors - understands patients’ plight.
“There is a lot of paranoia and a lot of speculation with very little
fundamental, convincing information,” he said.
The National Institutes of Health in the United States has put out a
call seeking proposals for studies into the issue. An independent
consortium of researchers has launched a global study to analyze health
records for thousands of COVID-19 patients in the United States, Europe
and Asia. That project is part of the Observational Health Data Sciences
and Informatics program, an open-source research platform that enables
large-scale studies.
Dr Marc Suchard - a biostatistician at the University of California, Los
Angeles who is leading the study - said that it aims to determine
whether the medicines make infections more likely or more severe - or,
by contrast, whether they help protect against the virus. Suchard said
he expects a preliminary report within two weeks.
![](http://archives.lincolndailynews.com/2020/Apr/23/images/ads/current/topflight_sda_SFARM_2020.png)
MORE TARGETS FOR THE VIRUS
There is evidence that the drugs may increase the presence of an enzyme
- ACE2 - that produces hormones that lower blood pressure by widening
blood vessels. That's normally a good thing. But the coronavirus also
targets ACE2 and has developed spikes that can latch on to the enzyme
and penetrate cells, researchers have found. So more enzymes provide
more targets for the virus, potentially increasing the chance of
infection or making it more severe.
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![](../images/042320pics/news_n23.jpg)
A member of the French Civil Protection service measures blood
pressure of a man suspected of being infected with the coronavirus
disease (COVID-19), as its spread continues, in Paris, France, April
5, 2020. REUTERS/Benoit Tessier/File Photo
![](../images/ads/current/fitzpatrick_lda_SPONSOR_2017.png)
Other evidence, however, suggests the infection's interference with
ACE2 may lead to higher levels of a hormone that causes
inflammation, which can result in acute respiratory distress
syndrome, a dangerous build-up of fluid in the lungs. In that case,
ARBs may be beneficial because they block some of the hormone’s
damaging effects.
Novartis International AG and Sanofi SA are among the major
drugmakers selling ACE inhibitors and ARBs.
![](http://archives.lincolndailynews.com/2020/Apr/23/images/ads/current/Applegate_exc_sda_daily_030415.png)
Sanofi spokesman Nicolas Kressmann said that patients should consult
their doctors on whether to continue taking the drugs but that the
company has found insufficient evidence that they worsen COVID-19
through its own assessment of available scientific data.
The company reviewed several recent studies from China that came to
conflicting conclusions about whether COVID-19 patients with
hypertension fare worse than other patients, he said.
Novartis has not issued any guidance to clinicians or patients and
defers to scientists studying the issue, said spokesman Eric Althoff.
Researchers and doctors generally agree that people with severe
hypertension or heart failure should keep taking the drugs because
of the high risks of stopping. The debate centers on how to advise
the many patients with milder conditions who take the drugs. Two
camps have emerged - one calling for no action unless the drugs are
proven dangerous, the other for some limits on their use until they
are proven safe.
The Centre for Evidence-Based Medicine at University of Oxford in
England has recommended that clinicians consider withdrawing the
medicines in patients with mild hypertension if they are in a high
risk group, such as medical workers - and replacing them with
alternative blood pressure-lowering drugs.
The New England Journal of Medicine (NEJM) took the opposite tack,
highlighting the drugs’ potential in fighting coronavirus and
recommending patients continue taking the drugs until more about the
risks is known. Several of the scientists who co-authored it had
done extensive, industry-supported research on antihypertensive
drugs.
CONFLICTS OF INTEREST
Dr Kevin Kavanagh, founder of Health Watch USA, a patient advocacy
organization, questioned whether scientists who are funded by the
drug industry should be advising clinicians, given the high stakes.
![](http://archives.lincolndailynews.com/2020/Apr/23/images/ads/current/hartsburggrain_sda_2019.png)
“You need to consider stepping back, and let others without a
conflict of interest try to make a call,” Kavanagh said.
His organization recommends that doctors temporarily avoid putting
new patients on the drugs and warn those currently on them to take
extreme precautions to avoid virus exposure.
Dr Scott David Solomon, a co-author of the NEJM article, conducts
industry-financed research but said it has no influence on his
position.
“Not only is there no compelling evidence that we should be
discontinuing those medications, but there's reason to think that
doing so might actually cause harm,” said Solomon, who is the
director of noninvasive cardiology at Brigham and Women’s Hospital
in Boston.
The lack of consensus leaves doctors to navigate the issue patient
by patient. Alexander, of Johns Hopkins, is trying to strike a
balance in his own practice. Patients with more severe
blood-pressure problems may need to keep taking the medicines, he
said, while patients with milder or newly diagnosed cases could
instead take one of the “literally dozens” of alternative
hypertension treatments.
“Rest assured,” he said, “there are dozens of scientific teams
working feverishly to put this question to bed.”
(Reporting by Deborah Nelson; Editing by Brian Thevenot)
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