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

229 The impact of the EIA clinic on early RA care

Background: Trials indicate early intervention and tight disease control in rheumatoid arthritis (RA) associate with improved outcomes. This is reflected in the NICE quality statements for early RA care, and in the Best Practice Tariff for RA. Many service providers have adopted a dedicated early inflammatory arthritis (EIA) clinic to meet national guidance. Uptake of this model is not universal and its impact has not been studied in the real world setting. The aim of this analysis was to assess the impact of an EIA clinic service model on performance, using the National Clinical Audit (NCA) of EIA.Methods: The NCA was conducted to assess early RA care. All NHS providers in England and Wales were required to participate. Follow up data were captured over three months. Trust and patient level variables were collected. Patients with a confirmed diagnosis of inflammatory arthritis were included. The mean times from first presentation with symptoms to rheumatology referral (referral time), and from receipt of referral to first rheumatology clinic visit (rheumatology clinic review time) for each Trust were calculated. The analysis assessed the relationship between the presence of an EIA clinic and referral times. We also examined potential confounding influences of Trust and patient level characteristics through regression modelling.Results: Of 146 eligible Trusts, 137 provided data. 7340 patients were diagnosed with inflammatory arthritis. 7313 were seen at Trusts that provided EIA clinic information. 77/137 (56%) Trusts offered an EIA clinic, and had significantly shorter referral and rheumatology clinic review times (see table). This was maintained after adjustment. Considering case-mix, only deprivation as measured by index of multiple deprivation (IMD) differed between centres (higher average deprivation in centres with no EIA clinic).Tender and swollen joint count at diagnosis didn't correlate with referral time.Conclusion: Access to EIA clinics varies nationally. The presence of an EIA service correlates with reduced delays both in primary and secondary care. Previous work from the NCA has shown that timely rheumatology review associates with improved outcomes. This supports the value of a dedicated early arthritis service model. The factors that constitute a successful EIA clinic require further characterisation