Early in the COVID-19 pandemic, there were concerns that a type of drug primarily used for treating hypertension (high blood pressure) might worsen the infection.
The drugs in question are angiotensin-converting enzyme inhibitors (ACE inhibitors) and angiotensin receptor blockers (ARBs).
Both classes of drugs work by interacting with ACE2, a receptor found on the surface of cells involved in regulating blood pressure. These receptors are a common feature on cells throughout both the cardiovascular and respiratory systems.
SARS-CoV-2, the virus that causes COVID-19, uses ACE2 to gain entry to its host cells in the human body. Some scientists speculated that taking ACE inhibitors or ARBs could increase the number of these receptors and therefore exacerbate the infection.
In May 2020, Medical News Today reported a relatively small study that found no link between taking the drugs and the risk of developing COVID-19.
Now, researchers in the United Kingdom have pooled data from 19 studies in the largest meta-analysis to investigate this question. Their work provides further reassurance that the drugs do not increase the risk of severe COVID-19 or death from the infection.
The study suggests that long-term use of the medications — which people with other cardiovascular diseases also take — could reduce infection severity and improve survival.
The study features in the latest issue of Current Atherosclerosis Reports.
Critical events and survival
Researchers at the University of East Anglia (UEA) in Norwich, U.K., collaborated with the Norfolk and Norwich University Hospital to analyze data on 28,872 patients with COVID-19.
They focused on patients admitted to the intestine care unit who experienced “critical events,” such as being on a ventilator.
One-third of the patients had hypertension, and one-quarter of all the patients were taking an ACE inhibitor or an ARB.
These large proportions among patients are likely the result of an increased risk of severe COVID-19 among individuals with cardiovascular disease, hypertension, and diabetes, says lead researcher Dr. Vassilios Vassiliou of UEA’s Norwich Medical School.
“But the really important thing that we showed was that there is no evidence that these medications might increase the severity of COVID-19 or risk of death,” says Dr. Vassiliou.
“On the contrary, we found that there was a significantly lower risk of death and critical outcomes, so they might, in fact, have a protective role — particularly in patients with hypertension.”
Among patients with hypertension who were taking the drugs, the odds of becoming critically ill or dying were 33% lower than patients with hypertension who were not taking them.
The results also suggest that there might be a reduced risk among all patients taking the drugs, including those taking them for other cardiovascular conditions. However, this finding was not statistically significant.
“As the world braces itself for a potential second wave of the infection, it is particularly important that we understand the impact that these medications have in COVID-19 patients. Our research provides substantial evidence to recommend continued use of these medications if the patients were taking them already.” – Dr. Vassilios Vassiliou
However, he emphasizes that the study did not investigate whether giving these drugs to other patients with COVID-19 might improve their outcome. The effects of ACE inhibitors and ARBs in COVID-19 patients who are not already taking them are unknown.
The authors note that early in the pandemic, despite doctors recommending that patients continue to take ACE inhibitors and ARBs for cardiovascular disease, some stopped taking them after reading reports of a possible risk.
“Although cardiovascular diseases in combination with COVID-19 portend increased risk of severity and mortality, the use of [ACE inhibitors and ARBs] is not the likely culprit,” they emphasize.
They acknowledge that a limitation of their analysis was that it looked at data from retrospective, observational studies. To draw definitive conclusions would require clinical trials comparing patients randomly assigned either to take the drugs or to a control group
Stephen Evans, a professor of pharmacoepidemiology at the London School of Hygiene and Tropical Medicine in the U.K., agreed that only clinical trials could provide definitive evidence of the drugs’ effects in COVID-19.
Speaking to the Science Media Centre in London, Prof. Evans said:
“These data do provide some reassurance that those who need these drugs for their high blood pressure should continue using them. COVID-19 is not the only disease that older people will die of during a pandemic, and the benefits of the drugs on other, non-COVID-19, outcomes may be important.”