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0 0.5 1 1.5 2+ Death/mechanical ventil.. 84% Improvement Relative Risk Death/mechanical ve.. (b) 89% Death/hospitalization 54% Death/hospitalization (b) 80% Lewnard et al. Paxlovid for COVID-19 EARLY TREATMENT Is early treatment with paxlovid beneficial for COVID-19? Retrospective study in the USA (December 2021 - April 2022) Lower death/ICU (p=0.027) and death/hosp. (p=0.031) Lewnard et al., The Lancet Infectious Diseases, doi:10.1016/S1473-3099(23)00118-4 Favors paxlovid Favors control

Effectiveness of nirmatrelvir–ritonavir in preventing hospital admissions and deaths in people with COVID-19: a cohort study in a large US health-care system

Lewnard et al., The Lancet Infectious Diseases, doi:10.1016/S1473-3099(23)00118-4
Lewnard et al., Effectiveness of nirmatrelvir–ritonavir in preventing hospital admissions and deaths in people with COVID-19:.., The Lancet Infectious Diseases, doi:10.1016/S1473-3099(23)00118-4
Mar 2023   Source   PDF  
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Retrospective 7,274 outpatients in the USA treated with paxlovid and matched controls, showing lower combined hospitalization/death with treatment.
With a small percentage of eligible patients receiving treatment, confounding by indication, healthcare seeking behavior, knowledge of COVID-19 treatments, etc. is likely significant. Authors partially address this in their matching procedure. Notably, authors do not appear to address confounding by contraindication, and matching is unable to find a match for patients that seek adjuvant treatments (e.g., paxlovid + vitamin D). Confounding may be more significant for patients that seek care earlier.
Confounding by treatment propensity. This study analyzes a population where only a fraction of eligible patients received the treatment. Patients receiving treatment may be more likely to follow other recommendations, more likely to receive additional care, and more likely to receive adjuvant treatments that are not tracked in the data (e.g., nasal/oral hygiene [, (B)], vitamin D [ (C)], etc.) — either because the physician recommending paxlovid also recommended them, or because the patient seeking out paxlovid is more likely to be familiar with the efficacy of additional treatments. Therefore, these kind of studies may overestimate the efficacy of treatments.
Confounding by contraindication. [Hoertel] find that over 50% of patients that died had a contraindication for the use of Paxlovid. Retrospective studies that do not exclude contraindicated patients may significantly overestimate efficacy.
death/mechanical ventilation/ICU, 84.1% lower, RR 0.16, p = 0.03.
death/mechanical ventilation/ICU, 89.2% lower, RR 0.11, p = 0.07, within 5 days.
risk of death/hospitalization, 53.6% lower, RR 0.46, p = 0.03.
risk of death/hospitalization, 79.6% lower, RR 0.20, p = 0.008, within 5 days.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Lewnard et al., 15 Mar 2023, retrospective, USA, peer-reviewed, 12 authors, study period 31 December, 2021 - 7 April, 2022.
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Effectiveness of nirmatrelvir–ritonavir in preventing hospital admissions and deaths in people with COVID-19: a cohort study in a large US health-care system
Dr Joseph A Lewnard, PhD John M Mclaughlin, Debbie Malden, Vennis Hong, PhD, L Jodar PhD Laura Puzniak, MD Bradley K Ackerson, Bruno J Lewin, PhD Jeniffer S Kim, Sally F Shaw, Harpreet Takhar, Luis Jodar, Sara Y Tartof
The Lancet Infectious Diseases, doi:10.1016/s1473-3099(23)00118-4
Background In the USA, oral nirmatrelvir-ritonavir is authorised for use in patients aged 12 years or older with mildto-moderate COVID-19 who are at risk of progression to severe disease and hospitalisation. We aimed to establish the effectiveness of nirmatrelvir-ritonavir in preventing hospital admissions and death in people with COVID-19 in an outpatient prescribing context in the USA. Methods In this matched observational outpatient cohort study in the Kaiser Permanente Southern California (CA, USA) health-care system, data were extracted from electronic health records of non-hospitalised patients aged 12 years or older who received a positive SARS-CoV-2 PCR test result (their index test) between April 8 and Oct 7, 2022, and had not received another positive test result within the preceding 90 days. We compared outcomes between people who received nirmatrelvir-ritonavir and those who did not receive nirmatrelvir-ritonavir by matching cases by date, age, sex, clinical status (including care received, the presence or absence of acute COVID-19 symptoms at testing, and time from symptom onset to testing), vaccination history, comorbidities, health-care seeking during the previous year, and BMI. Our primary endpoint was the estimated effectiveness of nirmatrelvir-ritonavir in preventing hospital admissions or death within 30 days of a positive test for SARS-CoV-2. Findings 7274 nirmatrelvir-ritonavir recipients and 126 152 non-recipients with positive SARS-CoV-2 tests were included in our study. 5472 (75•2%) treatment recipients and 84 657 (67•1%) non-recipients were tested within 5 days of symptom onset. Nirmatrelvir-ritonavir had an overall estimated effectiveness of 53•6% (95% CI 6•6-77•0) in preventing hospital admission or death within 30 days of a positive test for SARS-CoV-2, which increased to 79•6% (33•9-93•8) when nirmatrelvir-ritonavir was dispensed within 5 days of symptom onset. Within the subgroup of patients tested within 5 days of symptom onset and whose treatment was dispensed on the day of their test, the estimated effectiveness of nirmatrelvir-ritonavir was 89•6% (50•2-97•8). Interpretation In a setting with high levels of COVID-19 vaccine uptake, nirmatrelvir-ritonavir effectively reduced the risk of hospital admission or death within 30 days of a positive outpatient SARS-CoV-2 test.
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Bmi, None, kg/m²
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Please send us corrections, updates, or comments. Vaccines and treatments are complementary. All practical, effective, and safe means should be used based on risk/benefit analysis. No treatment, vaccine, or intervention is 100% available and effective for all current and future variants. We do not provide medical advice. Before taking any medication, consult a qualified physician who can provide personalized advice and details of risks and benefits based on your medical history and situation. FLCCC and WCH provide treatment protocols.
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