Discontinuing ACE inhibitor and angiotensin receptor blocker treatment for 30 days was not associated with improved survival among patients hospitalized with mild to moderate Covid-19 in a randomized clinical trial from Brazil.
The BRACE CORONA trial was the first randomized study to compare death and other outcomes among patients hospitalized with Covid-19 who did and did not discontinue the hypertension treatments.
Peer reviewed findings from the trial were published January 19 in JAMA, and they were first reported in early September at the virtual meeting of the European Society of Cardiology Congress.
The findings do not support routinely discontinuing angiotensin-converting enzyme inhibitors (ACE inhibitors) or angiotensin II receptor blockers (ARBs) in patients hospitalized with mild to moderate Covid-19, wrote researcher Renato D. Lopes, MD, PhD, of Duke University, Durham, North Carolina, and colleagues.
“In this pragmatic, registry-based randomized clinical trial, discontinuing ACE inhibitors or ARB therapy for 30 days did not affect the number of days alive and out of the hospital in patients hospitalized with mild to moderate Covid-19,” Lopes and colleagues wrote.
Because the SARS-CoV-2 virus acts through the angiotensin-converting enzyme 2 (ACE2) receptor, there was early speculation that RAAS inhibitors might increase Covid-19 risk or worsen symptoms in those infected.
The researchers noted that preclinical studies have shown up-regulation of ACE2 expression by RAAS inhibitors, while observational studies have largely shown better outcomes among Covid-19 patients taking ACE inhibitors and ARBs, “leading to speculation that ACE inhibitors and ARBs decrease acute lung damage and prevent angiotensin II-mediated pulmonary permeability, inflammation and fibrosis.”
They wrote that while conventional randomized clinical trials are optimal, the urgent need for Covid-19 treatments has necessitated innovative and more efficient research strategies.
“Prospective, registry-based randomized clinical trials are a reliable tool for managing cost-effective and efficient research, and might be an attractive approach in critical circumstances like the current Covid-19 pandemic.”
The study included 659 patients hospitalized for mild to moderate Covid-19 enrolled between April 9 and June 26, 2020. All were taking ACE inhibitors or ARBs prior to hospitalization for established hypertension. More than 50% were also obese.
A total of 334 patients were taken off the hypertension therapies and 325 continued on the drugs during hospitalization.
The primary study outcome was the number of days alive and out of the hospital through 30 days, and secondary outcomes included death, cardiovascular death, and Covid-19 progression. The median age of the patients was 55.1 years, 14.7% were age 70 or older, 40.4% were female and all participants completed the trial.
The median time from symptom onset to hospital admission was 6 days (IQR, 4-9 days) and 27.2% of patients had an oxygen saturation of less than 94% on room air at baseline. In all, 57.1% of patients were considered mild at hospital admission and 42.9% were considered moderate.
Among the main findings:
- No significant difference was observed in the number of days alive and out of the hospital in patients in the discontinuation group (mean, 21.9 days [SD, 8 days]) vs patients in the continuation group (mean, 22.9 days [SD, 7.1 days]) and the mean ratio was 0.95 (95% CI, 0.90-1.01).
- No statistically significant difference was observed in death (2.7% among the discontinuation group vs 2.8% among the continuation group [odds ratio [OR], 0.97; 95% CI, 0.38-2.52), cardiovascular death (0.6% vs 0.3%, respectively; OR, 1.95; 95% CI, 0.19-42.12) or Covid-19 progression (38.3% vs 32.3%; OR, 1.30; 95%CI, 0.95-1.80).
- The most common adverse events were respiratory failure requiring invasive mechanical ventilation (9.6% in the discontinuation group vs 7.7% in the continuation group), shock requiring vasopressors (8.4% vs 7.1%, respectively), acute myocardial infarction (7.5% vs 4.6%), new or worsening heart failure (4.2% vs 4.9%), and acute kidney failure requiring hemodialysis (3.3% vs 2.8%).
Study limitations cited by the researchers included the open-label design, which could lead to treatment bias; and the in-hospital randomization occurring a median of 2 days after admission, which could limit generalizability to Covid-19 patients in other settings. In addition, data on race, ethnicity, COPD, and immunosuppression were limited.
- Discontinuing ACE inhibitor and angiotensin receptor blocker treatment for 30 days was not associated with improved survival among patients hospitalized with mild to moderate Covid-19.
- The findings do not support routinely discontinuing ACE inhibitors or angiotensin II receptor blockers in patients hospitalized with mild-to moderate Covid-19.
Salynn Boyles, Contributing Writer, BreakingMED™
Lead researcher Renato Lopes reported receiving grant support from Bristol-Myers Squibb, GlaxoSmithKline, Medtronic, Sanofi, and Pfizer; and receiving consulting fees from Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi-Sankyo, GlaxoSmithKline, Medtronic, Merck, Pfizer, Sanofi, and Portola.
Cat ID: 125
Topic ID: 79,125,730,3,6,125,190,926,192,927,916,925,934