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0 0.5 1 1.5 2+ Mortality 50% Improvement Relative Risk Death/hospitalization 43% primary Paxlovid  Schwartz et al.  EARLY TREATMENT Is early treatment with paxlovid beneficial for COVID-19? Retrospective 177,545 patients in Canada (April - August 2022) Lower mortality (p<0.0001) and death/hosp. (p<0.0001) Schwartz et al., medRxiv, November 2022 Favors paxlovid Favors control

Real-world effectiveness of nirmatrelvir/ritonavir use for COVID-19: A population-based cohort study in Ontario, Canada

Schwartz et al., medRxiv, doi:10.1101/2022.11.03.22281881
Nov 2022  
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Retrospective 177,545 patients in Canada, 8,876 treated with paxlovid, showing lower mortality and hospitalization with treatment, and declining efficacy over the two time periods analyzed.
Confounding by contraindication. Hoertel et al. find that over 50% of patients that died had a contraindication for the use of Paxlovid Hoertel. Retrospective studies that do not exclude contraindicated patients may significantly overestimate efficacy.
Black box warning. The FDA notes that "severe, life-threatening, and/or fatal adverse reactions due to drug interactions have been reported in patients treated with paxlovid" FDA.
risk of death, 50.2% lower, RR 0.50, p < 0.001, treatment 142 of 8,876 (1.6%), control 5,566 of 168,669 (3.3%), NNT 59, odds ratio converted to relative risk, propensity score weighting.
risk of death/hospitalization, 43.1% lower, RR 0.57, p < 0.001, treatment 186 of 8,876 (2.1%), control 6,241 of 168,669 (3.7%), NNT 62, odds ratio converted to relative risk, propensity score weighting, primary outcome.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Schwartz et al., 5 Nov 2022, retrospective, Canada, preprint, mean age 74.0, 10 authors, study period 4 April, 2022 - 31 August, 2022.
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This PaperPaxlovidAll
Real-world effectiveness of nirmatrelvir/ritonavir use for COVID-19: A population-based cohort study in Ontario, Canada
Kevin L Schwartz, J Wang, M Tadrous, B J Langford, N Daneman, V Leung, T Gomes, L Friedman, P Daley, K A Brown
Background: Our objective was to evaluate the real world effectiveness of nirmatrelvir/ritonavir to prevent severe COVID-19 while Omicron and its subvariants predominate. Methods: We conducted a population based cohort study in Ontario, Canada including all residents >17 years of age who tested positive for SARS-CoV-2 by PCR between 4 April and 31 August 2022. We compared nirmatrelvir/ritonavir treated patients to unexposed patients and measured the primary outcome of hospitalization or death from COVID-19, and a secondary outcome of death 1-30 days. We used weighted logistic regression to calculate weighted odds ratios (wOR) with 95% confidence intervals (CIs) using inverse probability of treatment weighting (IPTW) to control for confounding. Results: The final cohort included 177,545 patients with 8,876 (5.0%) exposed and 168,669 (95.0%) unexposed individuals. The groups were well balanced with respect to demographic and clinical characteristics after applying stabilized IPTW. Hospitalization or death within 30 days was lower in the nirmatrelvir/ritonavir treated group compared to unexposed individuals (2.1% vs 3.7%, wOR 0.56; 95%CI, 0.47-0.67). In the secondary analysis, the relative odds of death was also significantly reduced (1.6% vs 3.3%, wOR 0.49; 95%CI, 0.39-0.62). The number needed to treat to prevent one case of severe COVID-19 was 62 (95%CI 43 to 80). Findings were similar across strata of age, DDIs, vaccination status, and comorbidities. Interpretation: Nirmatrelvir/ritonavir was associated with significantly reduced risk of hospitalization and death from COVID-19 in this observational study, supporting ongoing use of this therapeutic to treat patients with mild COVID-19 at risk for severe disease. .
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