Certain widely used medications that treat high blood pressure apparently don’t add to the danger as earlier feared. Recent studies suggest they don’t make people more susceptible to becoming infected with the coronavirus, nor do they exacerbate the disease. As a result, doctors who care for patients with hypertension have urged them to continue taking the drugs.
“I believe these medications do not make covid-19 worse,” says Karan Desai, a cardiology fellow at the University of Maryland Medical Center. “These medications treat hypertension and heart failure. But if these conditions worsen or go untreated, it will likely make covid-19 more severe if a patient contracts the virus.”
These findings are important because earlier reports raised questions about whether two frequently prescribed classes of blood pressure drugs, ACE inhibitors and angiotensin receptor blockers (ARBs), might actually make people more vulnerable to contracting the virus and cause an infection to become more virulent.
Nearly half of all American adults have high blood pressure, according to the Centers for Disease Control and Prevention. Blood pressure is the force of blood as it pushes against the walls of the arteries carrying blood from the heart to the rest of the body. Uncontrolled hypertension can damage vital organs, such as the heart, brain, kidneys and eyes, and lead to heart disease and stroke.
Many people don’t even know they have it, one reason it is known as a “silent killer.” Worldwide, it results in an estimated 10.4 million deaths annually, according to the International Society of Hypertension.
The two groups of drugs lower blood pressure by tinkering with a specific body system that regulates it. But in doing so, they also affect ACE2 enzymes, specific receptors that the virus uses to latch onto cells and infect them, especially in the lungs and gastrointestinal tract. The concern was that the drugs might be causing ACE2 molecules to proliferate, providing the virus with more targets and the opportunity to further spread infection.
The lack of clear answers about a virus that keeps delivering unexpected surprises — prompting ideas about its behavior to constantly change — underscores the plight many doctors have been facing as they try to provide sound advice to their patients about the safety of treatment options.
“The message from doctors and the media regarding these medications over the past few months has not been consistent,” Desai says. Early on, he says, he was haunted by “a nagging feeling that maybe I [was] causing harm. Patience has been hard. We all are hanging onto every piece of information. We all want answers, and we want them fast. The angst that comes with uncertainty and fear is understandable. As providers, we want to provide solutions. But as scientists, we have to be steadfast. We cannot make treatment decisions that are not grounded in science.”
So he and others were relieved at current evidence that shows the drugs do no harm. Some experts also believe ultimately they could prove beneficial.
“It may turn out that these agents may, in fact, even be protective, although we need additional research to confirm this,” says Robert T. Schooley, an infectious-disease specialist at the University of California at San Diego.
Schooley, himself past 60, has suffered from high blood pressure since he was in his 20s. In early April, he briefly stopped taking his ACE inhibitor, alarmed by early suspicions the drugs might worsen an infection.
“The idea that I was trading one danger for another was a frightening prospect,” Schooley says. “Nevertheless, I decided to stop until I had a chance to study all the evidence available. Since the effects of the drugs last for several days, I could allow the increased ACE receptor population to decay while I looked for more rigorous evidence about the potential connection.”
His drug break lasted four days. Schooley, also editor in chief of the journal Clinical Infectious Diseases, routinely reviews countless manuscripts related to the novel coronavirus. After finding no evidence that the drugs increased the risk of infection or severe illness, he resumed taking them.
Researchers continue to study the effect of these drugs on coronavirus infection and disease. But they also want to understand exactly what makes hypertension so dangerous for covid patients, including whether high blood pressure alone — that is, without additional underlying conditions — raises the risk.
People with hypertension have a twofold risk of dying from covid-19, and those with untreated high blood pressure have an even greater risk, according to one study, although experts don’t know why.
Many clinicians point out that patients with high blood pressure also have other factors that put them at risk of severe covid disease, including their age, obesity, diabetes, as well as other conditions in addition to hypertension that contribute to heart disease.
“I think it may be guilt by association,” says Sandra J. Taler, a specialist in hypertension at the Mayo Clinic. “Hypertension is a very common health problem that increases with age. The older you get, the more likely you are to have it. The people who most often get sick and die are those with coexisting conditions, which include hypertension, but I don’t think hypertension per se is the reason they are dying. I believe it’s just a marker of their age, and their health and the presence of other health problems.”
Stanley S. Liu, a cardiologist at the University of Maryland Medical Center, agrees. “Generally, patients with high blood pressure have a handicap anytime they experience serious illness,” he says. “This is because the organs affected by the serious illness already have compromised blood supplies due to long-standing high blood pressure, which makes them more vulnerable to serious damage.”
He believes this explains in part why many people experience severe disease or die, rather than the cause being “something new or different about covid-19 itself.” “I am more worried about the link between hypertension and problems in every organ system with a blood supply than I am about hypertension and covid-19 itself,” says Liu, who is also an assistant professor of medicine at the University of Maryland School of Medicine.
For now, experts agree that hypertension patients should continue with their drug regimens, as the current research concludes they pose no additional harm when it comes to covid-19. Studies have found no link between the medications and the risk of developing covid-19, or experiencing more severe symptoms, or that other blood pressure medications, such as calcium channel blockers, beta blockers and thiazide diuretics, raise the risks.
(The authors of another study that reached similar conclusions recently retracted their research following public concerns about the quality of the database they used.)
Robert Carey, a cardiovascular endocrinologist who is dean emeritus of the University of Virginia’s School of Medicine, says researchers are still studying whether patients on the drugs do fare better than those who don’t take them. He points out that the drugs help reduce chronic inflammation, a condition that can lead to serious health dangers.
“Hypertension is characterized by inflammation in blood vessels,” he says. “A viral infection, of course, also has inflammation as its main manifestation, in this case in the lungs.”
Meanwhile, numerous additional studies are gearing up or are already underway to seek answers to these questions and others. Researchers also are looking at the potential effect on covid-19 of blood thinners, statins, which lower cholesterol, antiplatelets, which prevent blood clots, and medications that lower triglycerides, a type of fat found in the blood that — in excess — can contribute to heart disease.
They also are studying other types of blood pressure drugs.
Researchers at Johns Hopkins’s Sidney Kimmel Comprehensive Cancer Center, for example, recently reported preliminary findings that suggest another blood pressure drug, Prazosin, an alpha blocker that relaxes blood vessels, targets what is known as cytokine storm, a syndrome that involves an extreme inflammatory response that afflicts older covid-19 patients with underlying health conditions.
It is associated with severe disease and an increased risk of death. They plan to conduct a larger clinical trial to determine whether early administration of the drug will reduce deaths among infected patients.
The University of Maryland plans to examine data from patient registries to learn more about the links between severe covid-19 complications, hypertension and diabetes, and also plans to study genetics involved in cardiovascular disease to see whether certain genes predispose a patient to greater risks.
UC San Diego scientists are planning to conduct a study to learn more about whether the drugs have a beneficial effect on patients with the disease.
University of Pennsylvania researchers also recently launched an international, multisite study to find out more about how ACE inhibitors and ARBS affect the covid-19 disease. They are cautious about the drugs’ effects until they finish their research.
“We have reason to think they may be helpful, and we have reason to think they might be harmful,” says Jordana B. Cohen, assistant professor in the University of Pennsylvania’s Perelman School of Medicine, one of the principal investigators. “We really don’t know.”
Her co-principal investigator, Julio Chirinos, agrees.
“They may help the virus. They may help the body. Or they may do nothing at all,” he says. “We need to find the answers. But until we do, there is no reason to stop taking these drugs.”
Carey agrees, saying the most important thing hypertensive patients can do during the pandemic is to keep their blood pressure under control.
“We don’t want people going off their medications because they think doing so might lessen their chances of getting covid-19, or of making it worse,” he says.