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

Heart failure and depression: A perspective from bibliometric analysis

Background: Depression commonly occurs in heart failure patients, and negatively influences quality of life and disease prognosis. This study explored heart failure and depression-related research from a bibliometric perspective. Methods: Relevant publications were searched on June 24, 2022. The Bibliometrix package in R was used to conduct quantitative analyses including the trends in publications, and related countries, articles, authors and keywords. VOSviewer software was used to conduct the visualization map on co-word, co-author, and institution co-authorship analyses. CiteSpace software was used to illustrate the top keywords with citation burst. Results: A total of 8,221 publications in the heart failure and depression related research field were published between 1983 and 2022. In this field, the United States had the most publications (N = 3,013; 36.65%) and highest total citation (N = 149, 376), followed by China, Germany, Italy and Japan. Author Moser and Duke University were the most productive author and institution, respectively. Circulation is the most influential journal. Apart from “heart failure” and “depression,” “quality of life,” “mortality” and “myocardial infarction” were the most frequently used keywords in this research area; whereas more recently, “self care” and “anxiety” have been used more frequently. Conclusion: This bibliometric analysis showed a rapid growth of research related to heart failure and depression from 1989 to 2021, which was mostly led by North America and Europe. Future directions in this research area include issues concerning self-care and anxiety about heart failure. As most of the existing literature were published in English, publications in other languages should be examined in the future