As part of an ongoing adaptive platform trial, investigators evaluated if initiating angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARB) improved outcomes in patients hospitalized with COVID-19, citing the theory that overactivation of the renin-angiotensin system (RAS) potentially drives worse outcomes.
However, ACE inhibitor or ARB therapy did not improve, and even likely worsened, outcomes in critically-ill patients hospitalized for COVID-19, according to the writing committee. Given the safety risks, the trial was terminated early and findings were not complete for the non-critically-ill and combined ARB and DMX-200 treatment subgroups. Data for this segment of the overarching REMAP-CAP study were presented in JAMA.
RAS Inhibitors Reduce COVID-19 Survival
Between March 2021 and February, 2022, the trial randomized 721 critically-ill and 58 non-critically-ill hospitalized adults with COVID-19 to receive either ACE inhibitor (n=257), ARB (n=248), ARB plus DMX-200 (n=10), or control (n=264).
By the time of enrollment discontinuation, 679 critically-ill patients with COVID-19 (35.2% female; median years of age, 56) were eligible for final analysis: 231 in the ACE group, 217 in the ARB group, and 231 controls. The final follow-up was June, 2022.
The primary end point was organ support-free days, a combination of hospital survival and days alive without cardiovascular or organ support through 21 days. Researchers used a bayesian cumulative logistic model to determine if any interventions improved COVID-19 outcomes.
Median organ support-free days was 10 (interquartile range [IQR], -1 to 16) in the ACE inhibitor group, 8 (IQR, -1 to 17) in the ARB group, and 12 (IQR, 0-17) in the control group. Compared with controls, ACE inhibitors and ARB had median adjusted odds ratios of 0.77 (95% CI, 0.58-1.06) and 0.76 (95% CI, 0.56-1.05), respectively, for improving clinical outcomes.
Researchers reported 166 of 231 (71.9%) critically-ill patients in the ACE group, 152 of 217 (70%) in the ARB group, and 182 of 231 (78.8%) in the control group survived hospitalization. The study estimated ACE inhibitor and ARB therapy worsened survival versus standard care with a posterior probability of 95.3% and 98.1%, respectively.
“In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes,” the authors summarized.