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

Quantitative analysis of coronary vessels with optimized intracoronary CT number.

BACKGROUND: Variability in intracoronary computed tomography (CT) number may influence vessel quantification. We confirmed the feasibility of a novel method for measuring vessel diameter and area using coronary CT angiography (CCTA) with an optimized intracoronary CT number, 350 HU. METHODS: We performed intravascular ultrasound (IVUS) imaging in 52 patients with significant stenosis detected by coronary CT angiography targeting 350 HU using a CT number-controlling system. We measured 0-to-0 HU distances in the cross-sectional coronary images of 32 patients. We analyzed the ratio of 0-to-0 HU distances in CT images to media-to-media distances in IVUS images (C:I ratio). The area of ≥0 HU for 103 representative points in the remaining 20 patients was compared to the area of the traced external elastic membrane (EEM) in IVUS images. RESULTS: There was a strong correlation between 0-to-0 HU distance in CT images and media-to-media diameter in IVUS images (r = 0.97, p<0.001). The C:I ratio was 1.1. EEM area was estimated by dividing the area of ≥0 HU by the square of C:I. There was also a strong correlation between the estimated EEM area and the EEM area in IVUS images (r = 0.95, p<0.001). CONCLUSIONS: Media-to-media diameter and EEM area can be estimated by CCTA targeting the optimized intracoronary CT number when blood vessel borders are defined at 0 HU

Controlling intracoronary CT number for coronary CT angiography

AbstractBackgroundControlling intracoronary computed tomography (CT) number for coronary CT angiography (CCTA) has been difficult.ObjectiveThe study assessed whether intracoronary CT number of CCTA could be estimated.MethodsOne hundred twenty six patients were randomly assigned to either CCTA with 30mL of contrast media (CM) following 5mL of CM at timing bolus or CCTA with 50mL of CM following 10mL of CM at timing bolus. The relationships between intracoronary CT number and patients’ characteristics and peak time and peak CT number at timing bolus in patients who showed valid time–density curve were analyzed in both groups. Then, the multiple regression equation best described was made. The prediction system was validated by 112 patients randomly targeted between 250HU and 430HU of CT number.ResultsIn group 5/30, intracoronary CT number was positively correlated with peak CT number at timing bolus (correlation coefficient, 1.42, p<0.001), negatively correlated with body surface area (−109.19, p<0.001) and peak time (−6.93, p<0.001). Whereas, intracoronary CT number was positively correlated with only peak CT number at timing bolus (1.33, p<0.001) in group 10/50. Then, CT number-controlling system using the simple equation best described CT number was established for CCTA following 5mL of CM at timing bolus. Of 112 patients, there was good correlation between target CT number and measured CT number (r=0.85, p<0.0001) in 96 patients (85.7%), having valid time–density curve at timing bolus.ConclusionsControlling CT number may be enabled by CT number-controlling system following 5mL of CM at timing bolus

Different traces (A, B), the region (C, D) and the image (E) of of the ≥0 HU.

<p>Different traces (A, B), the region (C, D) and the image (E) of of the ≥0 HU.</p

The correlation between 0-to-0 HU distance on MDCT (x) and media-to-media (IVUS) distance (y).

<p>The correlation between 0-to-0 HU distance on MDCT (x) and media-to-media (IVUS) distance (y).</p

The correlation between the estimated and the measured EEM area (A), and Bland-Altman plot (B).

<p>The correlation between the estimated and the measured EEM area (A), and Bland-Altman plot (B).</p