First Randomized Trial Supports Safety of Antihypertensives in COVID-19 Patients
Tue, April 20, 2021

First Randomized Trial Supports Safety of Antihypertensives in COVID-19 Patients



The first randomized trial of common heart drugs in COVID-19 patients finally presents its data. The trial results support the continuation of these drugs among patients. The results also called immediate guidelines for clinical settings.

The first randomized trial that observed the effects of anti-hypertensive medications in COVID-19 patients was conducted in Brazil. The BRACE CORONA trial found that maintaining these drugs benefited patients, rather than increase their likelihood of fatal outcomes. Investigators considered angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB) safe in mild or moderate COVID-19 cases. They presented their findings at the European Society of Cardiology (ESC) Congress 2020.


The Different Types of Heart Medications

For older adults, high blood pressure is a common chronic illness that needs to be managed. A properly managed hypertension can keep complications, such as heart attack and stroke, at bay. But there are several drugs doctors can prescribe to manage hypertension. The variation offers flexibility to those who are taking other medications for different illnesses. So, patients must understand what they cannot take with prescribed antihypertensive drugs.

According to the American Heart Association, a US-based non-profit organization, there are various classes of antihypertensives available. Diuretics, beta-blockers, ACE inhibitors, ARBs, alpha-blockers, central agonists, and vasodilators are some examples of antihypertensives. ACEi and ARB are highly common drugs prescribed to patients with high blood pressure.

ACEi contains ingredients that counter angiotensin, a chemical that narrows blood vessels. By reducing the production of angiotensin, blood vessels relax and open up that stabilize high blood pressure. ARB also targets angiotensin but in a different way. Instead of reducing the levels of angiotensin, the drug blocks the receptor that can bind to the chemical. This ensures the failure of angiotensin to narrow the blood vessels.

According to Statista, the world consumes lots of antihypertensive doses every year. In 2017, Germany had the highest defined daily dose (DDD) at 593.1 per 1,000 people among member-nations of the Organization for Economic Cooperation and Development (OECD). It was followed by Hungary at 559.7, Czech Republic at 445.6, Finland at 439.1, and Slovenia at 402.8 DDD per 1,000 people. The five countries with the lowest consumption in that year were South Korea at 132, Turkey at 140.6, Latvia at 189.4, Israel at 202.6, and Luxembourg at 208.6 DDD per 1,000 people.


First Randomized Trial of Antihypertensives Among COVID-19 Patients

Research on COVID-19 showed how SARS-CoV-2 infects human cells. The coronavirus uses a lock-and-key mechanism via the ACE2 receptor. This receptor is highly common in human cells that enables the pathogen to infect a wide range of potential targets. But the coronavirus prefers to infect cells in the respiratory system. Because the mechanism is ACE2, many health experts expressed concern in the use of ACEi and ARBs among patients. There has been a conflict in observational evidence: some observed no issues while others identified safety concerns.

Recently, investigators of the BRACE CORONA trial presented their findings at ESC Congress 2020. Their findings might resolve the conflict in previous observational studies. They recommended the use of these medications during COVID-19 treatment, as much as possible. The recommendation was derived from the lack of safety concerns and notable differences in patient outcomes. ACEi and ARB were unlikely to lead COVID-19 patients to critical or fatal outcomes.

"This is the first randomised data assessing the role of continuing versus stopping ACE inhibitors and ARBs in patients with COVID-19. In patients hospitalised with COVID-19, suspending ACE inhibitors and ARBs for 30 days did not impact the number of days alive and out of hospital," said Renato Lopes, principal investigator of the trial and professor at Duke Clinical Research Institute, quoted non-profit organization ESC.

The conflict is centered around the ACE2 expression. Both ACEi and ARB are believed to increase the expression of ACE2. This may promote the ability of SARS-CoV-2 to infect more healthy cells. By discontinuing either antihypertensive, the coronavirus may be hindered with limited ACE2 expression. But there is no enough clinical evidence in previous studies to solidify the idea. Divided, some doctors agreed with discontinuation while others did not.



The BRACE CORONA trial was a randomized study that tested two strategies to get more conclusive evidence. One strategy paused the intake of ACEi or ARB for 30 days. The other strategy sustained the intake of either drug for 30 days. These were done among patients who were regularly taking the drugs, and have been hospitalized and confirmed with COVID-19. The main outcome was: the number of days alive and out of the hospital after 30 days.

A total of 659 patients were enrolled in the trial. They were randomly assigned into two groups: paused and sustained. These patients were obtained from 29 sites in Brazil. After 30 days, investigators assessed patients for the primary outcome and mortality. Results unveiled that the average days of being alive and out of the hospital were 21.9 for the paused group. While the average days of being alive and out of the hospital were 22.9 for the sustained group. There was a difference of 1.1 days between the two groups.

The percentage of patients who were alive and got out of the hospital was 95% in the sustained group and 91.8% in the paused group. The mortality rate after 30 days was 2.8% in the sustained group, compared to 2.7% in the paused group. Though, the difference was not statistically significant.

Lopes said that there is no clear evidence of benefit in discontinuing ACEi or ARB among patients hospitalized for mild or moderate COVID-19. They should continue their medication unless another clinical reason has been found, which may promote adverse outcomes. The study findings only cover patients who have been taking the medications for an indication. The drugs are not proposed as treatment or prevention for COVID-19.

Millions of people worldwide depend on antihypertensive to live a quality life. Hopefully, the findings can convince the medical community to quickly draft new guidelines for those taking ACEi or ARB.