Evolving Real-World Effectiveness of Monoclonal Antibodies for Treatment of COVID-19 : A Cohort Study.

BACKGROUND: Treatment guidelines and U.S. Food and Drug Administration emergency use authorizations (EUAs) of monoclonal antibodies (mAbs) for treatment of high-risk outpatients with mild to moderate COVID-19 changed frequently as different SARS-CoV-2 variants emerged. OBJECTIVE: To evaluate whether early outpatient treatment with mAbs, overall and by mAb product, presumed SARS-CoV-2 variant, and immunocompromised status, is associated with reduced risk for hospitalization or death at 28 days. DESIGN: Hypothetical pragmatic randomized trial from observational data comparing mAb-treated patients with a propensity score-matched, nontreated control group. SETTING: Large U.S. health care system. PARTICIPANTS: High-risk outpatients eligible for mAb treatment under any EUA with a positive SARS-CoV-2 test result from 8 December 2020 to 31 August 2022. INTERVENTION: Single-dose intravenous mAb treatment with bamlanivimab, bamlanivimab-etesevimab, sotrovimab, bebtelovimab, or intravenous or subcutaneous casirivimab-imdevimab administered within 2 days of a positive SARS-CoV-2 test result. MEASUREMENTS: The primary outcome was hospitalization or death at 28 days among treated patients versus a nontreated control group (no treatment or treatment ≥3 days after SARS-CoV-2 test date). RESULTS: The risk for hospitalization or death at 28 days was 4.6% in 2571 treated patients and 7.6% in 5135 nontreated control patients (risk ratio [RR], 0.61 [95% CI, 0.50 to 0.74]). In sensitivity analyses, the corresponding RRs for 1- and 3-day treatment grace periods were 0.59 and 0.49, respectively. In subgroup analyses, those receiving mAbs when the Alpha and Delta variants were presumed to be predominant had estimated RRs of 0.55 and 0.53, respectively, compared with 0.71 for the Omicron variant period. Relative risk estimates for individual mAb products all suggested lower risk for hospitalization or death. Among immunocompromised patients, the RR was 0.45 (CI, 0.28 to 0.71). LIMITATIONS: Observational study design, SARS-CoV-2 variant presumed by date rather than genotyping, no data on symptom severity, and partial data on vaccination status. CONCLUSION: Early mAb treatment among outpatients with COVID-19 is associated with lower risk for hospitalization or death for various mAb products and SARS-CoV-2 variants. PRIMARY FUNDING SOURCE: None.

Outcomes of catheter-directed thrombolysis vs. standard medical therapy in patients with acute submassive pulmonary embolism.

BACKGROUND: Catheter-directed thrombolysis (CDL) is increasingly being used for the treatment of submassive and massive pulmonary embolism. Although this therapy has been shown to be effective at reducing right ventricle strain, the impact on clinical outcomes remains unclear. We therefore aimed to evaluate the outcomes of CDL compared to standard anticoagulation for submassive pulmonary embolism patients in a large cohort. METHODS: We conducted a retrospective observational study of consecutive patients with a primary diagnosis of submassive pulmonary embolism admitted to an intensive care unit within our health system between June 2014 and April 2016. We compared the outcome of patients treated with systemic anticoagulation (medical therapy) vs. catheter-based delivery of tissue plasminogen activator (tPA) (CDL). CDL patients were matched with medical therapy controls using a propensity-score matching algorithm based on the components of the simplified pulmonary embolism severity index (sPESI) score. RESULTS: Unadjusted mortality rates were 3.0% for CDL vs. 10.4% for medical therapy at 30 days and 8.1% for CDL vs. 22.9% for medical therapy at 1 year. In the propensity-score matched cohort, mortality rates were 3.1% for CDL vs. 6.1% for medical therapy at 30 days and 8.2% for CDL vs. 18.2% for medical therapy at 1 year. Length of stay was significantly shorter in the CDL group. The index admission bleeding and transfusion rates were not increased in the CDL group. CONCLUSIONS: In patients presenting with acute submassive pulmonary embolism who are admitted to an intensive care unit, the group treated with CDL experienced reduced mortality at 30 days and 1 year when compared to medical therapy without increase in bleeding. Further randomized studies are required to confirm these findings.

Outcomes of Heart Failure Admissions Under Observation Versus Short Inpatient Stay.

BACKGROUND: Patients with heart failure (HF) are admitted either under observation (OBS) or inpatient stays; however, there is little data on whether this designation reflects the clinical status of a patient, with significant logistical and financial implications. We sought to compare the outcomes of patients with HF admitted OBS versus inpatient stay (≤2 days; INPT). METHODS AND RESULTS: From January 1, 2008 to September 30, 2015, our multisite health system saw 21 339 unique patients totaling 52 493 hospital admissions with a primary diagnosis of HF. Patients were excluded if they underwent cardiac surgery (n=611), heart transplantation (n=187), or left ventricular assist device insertion (n=198), or if they died during hospitalization (n=1839). Of the remaining 50 654 discharges, 2 groups were identified: INPT group and OBS group. Outcomes were HF readmission, all-cause readmission, and all-cause mortality within 1 year of discharge. Hazard ratios were computed using the Andersen-Gill method in the Cox proportional-hazards model. A total of 8709 admissions (17%) occurred in the INPT group and 2648 admissions (5%) occurred in the OBS group. HF readmission rate at 1 year was 55.3% in INPT versus 66.5% in OBS (hazard ratio, 0.75; 95% confidence interval, 0.71-0.80; P<0.01). All-cause readmission rate at 1 year was 70.7% in INPT versus 82.5% in OBS (hazard ratio, 0.74; 95% confidence interval, 0.70-0.78; P<0.01). All-cause mortality at 1 year occurred in 25.2% of INPT versus 24.2% of OBS (hazard ratio, 1.03; 95% confidence interval, 0.95-1.12; P=0.46). CONCLUSIONS: HF admissions designated INPTs were associated with lower readmission rates and equivalent mortality to those designated OBS.