Back to Search
Start Over
Effect of Angiotensin-Converting Enzyme Inhibitor and Angiotensin Receptor Blocker Initiation on Organ Support-Free Days in Patients Hospitalized With COVID-19: A Randomized Clinical Trial.
- Source :
-
JAMA [JAMA] 2023 Apr 11; Vol. 329 (14), pp. 1183-1196. - Publication Year :
- 2023
-
Abstract
- Importance: Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19.<br />Objective: To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19.<br />Design, Setting, and Participants: In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non-critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022).<br />Interventions: Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days.<br />Main Outcomes and Measures: The primary outcome was organ support-free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes.<br />Results: On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support-free days among critically ill patients was 10 (-1 to 16) in the ACE inhibitor group (n = 231), 8 (-1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support-free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively).<br />Conclusions and Relevance: 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.<br />Trial Registration: ClinicalTrials.gov Identifier: NCT02735707.
- Subjects :
- Female
Humans
Male
Middle Aged
Bayes Theorem
Hospitalization
Critical Illness
Receptors, Chemokine antagonists & inhibitors
Angiotensin Receptor Antagonists pharmacology
Angiotensin Receptor Antagonists therapeutic use
Angiotensin-Converting Enzyme Inhibitors pharmacology
Angiotensin-Converting Enzyme Inhibitors therapeutic use
COVID-19 therapy
Renin-Angiotensin System drug effects
COVID-19 Drug Treatment methods
Subjects
Details
- Language :
- English
- ISSN :
- 1538-3598
- Volume :
- 329
- Issue :
- 14
- Database :
- MEDLINE
- Journal :
- JAMA
- Publication Type :
- Academic Journal
- Accession number :
- 37039790
- Full Text :
- https://doi.org/10.1001/jama.2023.4480