The study included patients that were hospitalized during the Omicron period and showed a significant reduction in mortality rates when treatments were combined across all levels of respiratory support.
Researchers retrospectively analyzed patient-level data from the PINC AI Healthcare Database (formerly known as the Premier Healthcare database), a large multi-center U.S. hospital database representing ~25% of yearly inpatient hospitalization across US, to identify adults hospitalized with a primary diagnosis of COVID-19 between December 2021 and April 2023 (Omicron period) who initiated remdesivir + dexamethasone or dexamethasone alone in the first 2 days of hospitalization.
Patients were matched 1:1 using propensity score matching and stratified by baseline supplemental oxygen requirements. The study’s primary outcome was 14- and 28-day all-cause in-hospital mortality.
The study analyzed 151,215 patients hospitalized for COVID-19 during the Omicron period. After propensity score matching, the cohort included 33,037 patients treated with remdesivir + dexamethasone, matched to 33,037 patients receiving dexamethasone alone.
The study showed significantly lower mortality rates for patients treated with remdesivir + dexamethasone across all oxygen supplemental groups. Among patients without the need of supplemental oxygen, remdesivir with dexamethasone vs dexamethasone alone was associated with a 21% and a 20% reduction in mortality risk at day 14 and 28, respectively (14-days, adjusted HR 0.79 [0.72-0.87], P<0.0001; 28-days, aHR 0.80 [0.74-0.88], P<0.0001). For patients receiving low-flow oxygen (LFO), the combination treatment was associated with a reduction in mortality risk of 30% and 26% at days 14 and 28, respectively, compared to dexamethasone alone (14-days, aHR 0.70 [0.64-0.77], P<0.0001; 28-days, aHR 0.74 [0.68-0.81], P<0.0001).
Similarly, among high-flow oxygen/non-invasive ventilation (HFO/NIV) patients, remdesivir and dexamethasone, compared to dexamethasone monotherapy was associated with a 31% and 29% reduction in the risk of mortality at days 14 and 28, respectively (14-days, aHR 0.69 [0.62-0.76], P<0.0001; 28-days, aHR 0.71 [0.65-0.78], P<0.0001). In the IMV/ECMO group, mortality reduction risk was 22% and 19% at 14 days and at 28 days for those receiving the combination, to dexamethasone alone (14-days, aHR 0.78 [0.64-0.94], P=0.0182; 28-days, aHR 0.81 [0.69-0.97], P=0.0182).
Cox proportional hazard model adjusted for age, admission month, intensive care unit vs general ward, and other COVID-19 medications (baricitinib, tocilizumab, oral antivirals) was used to assess time to 14- and 28-day in-hospital all-cause mortality, and adjusted hazard ratios and 95% confidence intervals were derived:
Additionally, the study highlighted a gap between real-world clinical practice and guideline recommendations. Of the 36,489 patients who started on dexamethasone monotherapy, 90% did not receive remdesivir during hospitalization, even though guidelines recommend its use. This suggests room for improvement in ensuring that more patients receive the recommended combination treatment to reduce mortality risk.
In summary, the study shows that combining remdesivir with dexamethasone significantly improves survival compared to dexamethasone alone. This benefit is observed in both patients who do not require supplemental oxygen and those with hypoxemia, highlighting the importance of including remdesivir in treatment protocols to enhance patient outcomes.
Key points
• The study showed that combining remdesivir with dexamethasone significantly reduces mortality rates in hospitalized COVID-19 patients, especially during the Omicron period, compared to dexamethasone alone.
• This combination therapy is effective across various levels of respiratory support, but many patients are not receiving remdesivir as recommended, highlighting the need for better adherence to treatment guidelines.
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