Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. 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). 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. 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. 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). 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. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

UAS Literary & Arts Journal

Proof copy provided by Tidal Echoes.Tidal Echoes presents an annual showcase of writers and artists who share one thing in common: a life surrounded by the rainforests and waterways of Southeast Alaska.A Note From Kaleigh Lambert -- A Note From Thomas Bay -- A Note From Andrew Lounsbury -- A Note From Emily Wall -- Another Morning like This -- Hardest to Love -- Reasons Why Pregnancy is Not My Idea of a Good Decision -- This Year in Haiku (a poem for you) -- Clean Get-Away -- Deflection of the Racism Curve -- On Prince of Wales Island -- Frontier Justice -- Researching in the Woods -- Reading the Waves -- Burial at Sea -- Interview with Featured Artist Nicholas Galanin -- Indian River -- Tactical Warfare -- Morning Stories -- Two Times the Girl -- You Bring Out the Korean Adoptee in Me -- The Heritage of Adam -- Search Engine -- Color Guard -- Red Dogs and Onions -- Life Support -- Atonement 2009 -- Ravens Rue The Day -- King -- French Graffiti -- Love and the Immune System -- Interview with Featured Author Heather Lende -- Ruth’s Last Fairy Ride -- Sweet Caroline -- Singing Together With One Voice -- Burying Jack June 2008 -- Brigid’s light: A Break from Rain -- 7 the first time we kissed -- Me and Tui at 13 -- Sunday school -- Amber, Lydia, and John -- My Core -- Cranberry Juice-A Family Ordeal -- Brown Fat Old -- Wait -- Burning Man -- I’m no daddy’s girl -- Paper Doll -- For Poppy -- For Mammy -- Last Days of War -- Act Like a Man -- Shift Change at the Theatre -- Kotzebue Harvest -- Echo Canyon -- Knowledge -- Author & Artist Biographie

Effect of Antiplatelet Therapy on Survival and Organ Support–Free Days in Critically Ill Patients With COVID-19

International audienc