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

Association of plasma biomarkers with cognitive function in persons with dementia and cognitively healthy in the Democratic Republic of Congo

Abstract Introduction This study investigates whether plasma biomarkers (Aβ42/40 and p‐tau 181), APS, as well as apolipoprotein E (APOE) proteotype predict cognitive deficits in elderly adults from the Democratic Republic of Congo. Methods Forty‐four with possible AD (pAD) and 41 healthy control (HC) subjects were screened using CSID and AQ, underwent cognitive assessment with the African Neuropsychology Battery (ANB), and provided blood samples for plasma Aβ42, Aβ40, Aβ42/40, and APOE proteotype. Linear and logistic regression were used to evaluate the associations of plasma biomarkers with ANB tests and the ability of biomarkers to predict cognitive status. Results Patients with pAD had significantly lower plasma Aβ42/40 levels, higher APS, and higher prevalence of APOE E4 allele compared to HC. Groups did not differ in levels of Aβ40, Aβ42, or P‐tau 181. Results showed that Aβ42/40 ratio and APS were significantly associated with African Naming Test (ANT), African List Memory Test (ALMT), and African Visuospatial Memory Test (AVMT) scores, while the presence of APOE E4 allele was associated with ANT, ALMT, AVMT, and APT scores. P‐tau 181 did not show any significant associations while adjusting for age, education, and gender. APS showed the highest area under the curve (AUC) value (AUC = 0.78, 95% confidence interval [CI]: 0.68–0.88) followed by Aβ42/40 (AUC = 0.75, 95% CI: 0.66–0.86) and APOE E4 (AUC = 0.69 (CI 0.57–0.81) in discriminating pAD from HC. Discussion These results demonstrate associations between select plasma biomarker of AD pathology (Aβ42/40), APS, and APOE E4 allele) and ANB test scores and the ability of these biomarkers to differentiate pAD from cognitively normal SSA individuals, consistent with findings reported in other settings

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

International audienc