Observational evidence has been conflicting1 and there have been some concerns raised that membrane-bound angiotensin-converting enzyme 2 (ACE2), the functional receptor for SARS-CoV-2,2 may be upregulated in patients using ACEis and ARBs.3 In contrast, other preliminary data suggest that renin-angiotensin-aldosterone system (RAAS) inhibitors may benefit patients with COVID-19 by decreasing acute lung damage and preventing angiotensin-II-mediated pulmonary inflammation. Given their widespread use, definitive evidence was needed to rule out any potential negative effects of ACEis/ARBs in patients hospitalised with COVID-19.
In a Hot Line at ESC Congress 2020 today, Principal Investigator, Professor Renato Lopes (Duke Clinical Research Institute, Durham, NC, USA) presented results from the first randomised trial to address this issue, the BRACE CORONA trial. From 29 sites in Brazil, 659 hospitalised patients with COVID-19 were enrolled who were all chronically using an ACEi or ARB. Patients who were using more than three antihypertensive drugs, or sacubitril/valsartan, or who were haemodynamically unstable at presentation were excluded. Patients were randomised to stopping the ACEi/ARB for 30 days or continuing the ACEi/ARB.
When considering the primary outcome, results were similar between the groups for the average number of days alive and out of hospital: 21.9 days for patients who stopped ACEis/ARBs and 22.9 days for patients who continued these medications (hazard ratio [HR] 0.95; 95% confidence interval [CI] 0.90 to 1.01; p=0.09). The average difference between groups was –1.1 days (95% CI –2.33 to 0.17).
The proportion of patients alive and out of hospital by the end of 30 days in the suspending ACEis/ARBs group was 91.8% vs. 95.0% in the continuing group. A similar 30-day mortality rate was seen for patients who continued vs. those who suspended the ACEis/ARBs (2.8% vs. 2.7%, respectively, with an HR of 0.97).
Prof. Lopes concluded, “Because these data indicate that there is no clinical benefit from routinely interrupting these medications in hospitalised patients with mild to moderate COVID-19, they should generally be continued for those with an indication.”