Hypertension drugs are at the center of COVID-19 research

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(Reuters) – Scientists are baffled by the way the coronavirus attacks the body – killing many patients while barely affecting others.

FILE PHOTO: A member of the French Civil Protection measures the blood pressure of a man suspected of being infected with coronavirus disease (COVID-19), while its spread continues, in Paris, France, on April 5 2020. REUTERS / Benoit Tessier / File photo

But some are tempted by a clue: a disproportionate number of patients hospitalized with COVID-19, the disease caused by the virus, have high blood pressure. Theories about why the disease makes them more vulnerable – and what patients should do about it – have sparked a heated debate among scientists about the impact of widely prescribed blood pressure drugs.

Researchers agree that life-saving drugs affect the same pathways that the new coronavirus takes to enter the lungs and heart. They differ depending on whether these drugs open the door to the virus or protect against it. Resolving this issue took on a new urgency after an April 8 report from the United States Centers for Disease Control and Prevention showed that 72% of COVID-19 inpatients 65 years of age or older had hypertension.

The drugs are known as ACE inhibitors and ARB, broad categories that include Vasotec, Valsartan, Irbesartan, as well as their generic versions. In a recent interview with a medical journal, Anthony Fauci – America’s largest infectious disease expert – cited a report showing similar rates of hypertension in COVID-19 patients who died in Italy and suggested the drugs, rather that the underlying condition, can act as an accelerator for the virus.

Efforts to understand how the virus uses the heart and lungs pathway, and the role of drugs, are complicated by the lack of rigorous studies.

“There are millions of Americans who take an ACE inhibitor or AR on a daily basis,” 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.”

It is estimated that 100 million American residents suffer from high blood pressure, which increases the risk of heart disease, stroke and kidney failure. According to the CDC, about four-fifths of them need prescription medication to control it. ACE inhibitors and ARBs are widely prescribed for patients with congestive heart failure, diabetes or kidney disease. Drugs account for billions of dollars in prescription sales worldwide.

The lack of clear answers on the impact of drugs on COVID-19 patients has sparked unrestrained speculation in correspondence and editorials published on medical journal websites and those where scientists share drafts of pre-publication studies. not revised.

Many patients wonder if their medication will help or hurt them. Doris Kertzner, 88, of Redding, Connecticut, said that she carefully followed experts’ directions to prevent infections and keep her distance from other members of her retirement community. Now she has a new worry: she is taking losartan, an ARB, and cannot decide to stop.

Dropping the drug “presents its own problems” in dealing with high blood pressure.

“It has become very complicated,” she said.

Dr. Carlos M. Ferrario – a researcher at Wake Forest University School of Medicine and co-author of widely cited studies on ACE inhibitors – understands the plight of patients.

“There is a lot of paranoia and a lot of speculation with very little basic and convincing information,” he said.

The United States National Institutes of Health has launched a call for research proposals on the issue. An independent consortium of researchers has launched a global study to analyze the health records of thousands of COVID-19 patients in the United States, Europe and Asia. This 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 – biostatistician at the University of California at Los Angeles who is leading the study – said it was aimed at determining whether the drugs make infections more likely or more serious – or, on the other hand, whether they help to protect against the virus. Suchard said he expects a preliminary report within two weeks.

MORE TARGETS FOR VIRUS

There is evidence that drugs can increase the presence of an enzyme – ACE2 – which produces hormones that lower blood pressure by widening blood vessels. This is normally a good thing. But the coronavirus also targets ACE2 and has developed spikes that can cling to the enzyme and enter cells, researchers found. So more enzymes provide more targets for the virus, potentially increasing the risk of infection or making it worse.

Other evidence suggests, however, that interference from infection with ACE2 can lead to increased levels of an inflammation-causing hormone, which can lead to acute respiratory distress syndrome, a dangerous build-up of fluid in lungs. In this case, ARBs can be beneficial because they block some of the harmful effects of the hormone.

Novartis International AG and Sanofi SA are among the leading manufacturers of drugs selling ACE and ARB inhibitors.

Sanofi spokesman Nicolas Kressmann said patients should consult their doctors to find out if they should continue taking the drugs, but the company has found insufficient evidence of worsening COVID-19 due to its own assessment of available scientific data.

The company has reviewed several recent studies from China that have come to conflicting conclusions that COVID-19 hypertension patients fare worse than other patients, he said.

Novartis has not issued any guidelines for clinicians or patients and relies on the scientists studying the matter, said spokesman Eric Althoff.

Researchers and doctors generally agree that people with severe hypertension or heart failure should continue taking the medication because of the high risk of stopping it. The debate centers on how to counsel the many patients with milder conditions who are taking the drugs. Two camps have emerged – one calling for no action unless the drugs are proven to be dangerous, the other with certain limits on their use until proven safe.

The Center for Evidence-Based Medicine at the University of Oxford in England has recommended that clinicians consider withdrawing medication from patients with mild hypertension if they are part of a high-risk group, such as medical workers – and replace them with other antihypertensive drugs. .

The New England Journal of Medicine (NEJM) took the opposite position, highlighting the potential of the drugs in the fight against coronaviruses and recommending that patients continue taking the drugs until the risks are known. Several of the scientists who co-authored it had done extensive and industry-supported research on antihypertensive drugs.

CONFLICTS OF INTEREST

Dr. Kevin Kavanagh, founder of Health Watch USA, a patient advocacy organization, wondered whether scientists funded by the pharmaceutical industry should advise clinicians, given the high stakes.

“You should consider stepping back and letting others without a conflict of interest try to make a call,” said Kavanagh.

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 exposure to the virus.

Dr. Scott David Solomon, co-author of the NEJM article, is conducting industry-funded research, but said it had no influence on his position.

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“Not only is there no convincing evidence that we should stop these drugs, but there is reason to believe that it could actually be harmful,” said Solomon, director of non-invasive cardiology at Brigham and Women’s Hospital at Boston.

The lack of consensus leaves doctors to navigate patient by patient. Alexander, of Johns Hopkins, tries to find a balance in his own practice. Patients with more severe blood pressure problems may need to continue taking the drugs, he said, while patients with milder or newly diagnosed cases may instead take one of the “dozen” alternative treatments for hypertension.

“Rest assured,” he said, “dozens of science teams are working feverishly to resolve this issue. “

Deborah Nelson report; Editing by Brian Thevenot

Our standards:Principles of the Thomson Reuters Trust.

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