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 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.
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.
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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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.
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.
“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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