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

The Witan, 1975-1976 Academic Year V. 3 No. 8, April 1976

Advertising in Philadelphia Whither Thou Goest ABA?, Federal Penal Code Proposed, Nursing School, Save Yourself the Trouble, Rehabilitation Examined, New Faculty Appointments, Ascent of Man, One for the Road, Buen Provencho, Academy Lauds Show Zanuck to

The Witan, 1975-1976 Academic Year V. 3 No. 8, April 1976

Advertising in Philadelphia Whither Thou Goest ABA?, Federal Penal Code Proposed, Nursing School, Save Yourself the Trouble, Rehabilitation Examined, New Faculty Appointments, Ascent of Man, One for the Road, Buen Provencho, Academy Lauds Show Zanuck to

The Witan, 1977-1978 Academic Year V. 5 No. 2, September 1977

Nursing Care Abuse, The Lawyer as an Advocate, Viewpoints The Paper Law Student, Panama Canal Treaty, Freshmen Elections, Placement News, Seminar Scheduled, Golden Jubilee Red Mass, Journal Notes, Skinned Knees, Lexis, Looking for Outlines, Uncle Jimmy G

K/DOQI Clinical Practice Guidelines on Hypertension and Antihypertensive Agents in Chronic Kidney Disease

INTRODUCTION: CHRONIC KIDNEY disease (CKD) is a worldwide public health issue. In the United States, there is a rising incidence and prevalence of kidney failure (Fig 1), with poor outcomes and high cost. The prevalence of earlier stages of CKD is approximately 100 times greater than the prevalence of kidney failure, affecting almost 11% of adults in the United States. There is growing evidence that some of the adverse outcomes of CKD can be prevented or delayed by preventive measures, early detection, and treatment. Hypertension is a cause and complication of CKD. Hypertension in CKD increases the risk of important adverse outcomes, including loss of kidney function and kidney failure, early development and accelerated progression of cardiovascular disease (CVD), and premature death. In the ongoing effort to improve outcomes of CKD, the National Kidney Foundation (NKF) Kidney Disease Outcomes Quality Initiative (K/DOQI) appointed a Work Group and an Evidence Review Team in 2001 to develop clinical practice guidelines on hypertension and use of antihypertensive agents in CKD. During this same time, clinical practice guidelines on this topic relevant to CKD were also under development by other organizations, including the Seventh Report of the Joint National Committee on the Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) and the 2003 report of the American Diabetes Association (ADA) on the Treatment of Hypertension in Adults with Diabetes. The Work Group maintained contact with these organizations during development of these guidelines. The purpose of the Executive Summary is to provide a "stand-alone" summary of the background, scope, methods, and key recommendations, as well as the complete text of the guideline statements. Most tables and figures in the Executive Summary are taken from other sections of the document. BACKGROUND: Chronic Kidney Disease: Figure 2 is a conceptual model of CKD, which defines stages of CKD, as well as antecedent conditions, outcomes, risk factors for adverse outcomes, and actions to improve outcomes. CKD is defined as kidney damage, as confirmed by kidney biopsy or markers of damage, or glomerular filtration rate (GFR