BRACE CORONA advocates continuing ACEis/ARBs in mild-to-moderate COVID-19

Patients hospitalized with mild-to-moderate COVID-19 who are on angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) for hypertension should continue these medications, according to primary results of the BRACE CORONA trial presented at ESC 2020.

“In patients hospitalized with COVID-19, suspending ACE inhibitor/ARB therapy for 30 days did not impact the number of days alive and out of hospital,” presented principal investigator Professor Renato Lopes from the Duke Clinical Research Institute, Durham, North Carolina, US.

“Because these data indicate that there is no clinical benefit from routinely suspending these medications in hospitalized patients with mild-to-moderate COVID-19, they should be generally continued for those with an indication,” said Lopes.

Participants in this multicentre, phase IV Brazil-based trial were 659 adults (mean age 55.7 years, 40.4 percent female, mean BMI 31.0 kg/m²) hospitalized with a confirmed diagnosis of COVID-19 and who were chronic users of ACE inhibitors/ARBs. They were randomized to either temporarily suspend their use of ACE inhibitors/ARBs for 30 days (n=334) or continue with their medications (n=325).

Patients hospitalized for decompensated heart failure in the past year, those on sacubitril/valsartan or >3 antihypertensive medications, and those with haemodynamic instability in the first 24 hours until confirmation of COVID-19 diagnosis were excluded.

About half the patient population was obese (52.2 percent) and 31.9 percent had diabetes, while few patients had heart failure or kidney disease (1.4 percent each). At hospital admission, patients were primarily on ARBs (83.3 percent) and 16.7 percent were on ACE inhibitors. Patients had a median 5 years duration of use of these drugs. Other medications included beta blockers (14.6 percent), calcium channel blockers (18.2 percent), and diuretics (31.1 percent). 

The most common presenting symptoms of COVID-19 were cough (70.3 percent), fever (69.5 percent), and dyspnoea (53.7 percent), with patients experiencing symptoms a median 6 days prior to admission. In the first 24 hours of admission, most patients had either mild (57.1 percent) or moderate (42.9 percent) COVID-19, with no incidence of severe COVID-19 (due to exclusion criteria).

At 30 days, number of days alive and out of hospital was comparable between patients who suspended and continued ACE inhibitors/ARBs (mean 21.9 vs 22.9 days; mean difference -1.1 days; mean ratio, 0.95; p=0.09). [ESC 2020, Hot Line session]

A similar proportion of patients who suspended or continued ACE inhibitors/ARBs were alive and out of hospital at day 30 (91.8 percent vs 95.0 percent). The median number of days alive and out of hospital at 30 days was 25 days in both groups.

There were nine deaths in each group during the trial. All-cause mortality at 30 days did not significantly differ between patients who suspended or continued their ACE inhibitors/ARBs (2.7 percent vs 2.8 percent; hazard ratio, 0.97, 95 percent confidence interval, 0.38–2.52; p=0.95).

 

Implications of BRACE CORONA

“COVID-19 has really changed our lives … and one of the issues raised is what to do with ARBs and ACE inhibitors because most patients are taking these [medications] because of cardiovascular disease,” said discussant Professor Gianfranco Parati from the University of Milan-Bicocca and San Luca Hospital, Milan, Italy. [https://www.youtube.com/watch?v=NqtjzX7iWZs, accessed 3 September 2020]

“There has been conflicting observational evidence about the potential impact of ACE inhibitors/ARBs on patients with COVID-19,” noted Lopes.

“On one hand, renin-angiotensin-aldosterone system (RAAS) inhibition is harmful. ACE inhibitors and ARBs could increase ACE-2 receptor expression and thus, enhance viral entry and binding leading to outcomes in patients with COVID-19,” said Lopes. [https://www.youtube.com/watch?v=z9GxFTBFdPQ, accessed 3 September 2020]

“On the other hand, preliminary data hypothesize that RAAS inhibitors could benefit patients with COVID-19 by decreasing acute lung damage and preventing angiotensin-II-mediated pulmonary inflammation,” he said.

“This is the first randomized data assessing the role of continuing vs stopping ACE inhibitors and ARBs in patients with COVID-19. Our findings constitute contemporary and high-quality randomized evidence to guide the care of patients with COVID-19,” Lopes said.

 

Not the whole story

Despite the positive results, issues remain, and analysing them may help clarify some of the findings, Parati pointed out.

The trial included a relatively young population of patients with mild or moderate COVID-19. “By selecting [patients with] relatively mild or moderate [COVID-19], with such a low mortality rate, in my opinion, the [researchers] could not really solve the issue,” he said.

There might also be differences in the outcomes between ACE inhibitors and ARBs. While the results are important because they were obtained from a randomized trial, they might “not be telling us the last words.”

“It might be nice to consider the interaction between age, comorbidities, and these treatments. That might tell us more,” concluded Parati.