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Proton Pump Inhibitor Use Is Not Strongly Associated With SARS-CoV-2 Related Outcomes: A Nationwide Study and Meta-analysis

Israelsen et al., Clinical Gastroenterology and Hepatology, doi:10.1016/j.cgh.2021.05.011, EUPAS35835
Sep 2021  
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Mortality, all patients 5% Improvement Relative Risk Mortality, within cases 12% Ventilation, all patients -8% Ventilation, within cases 0% ICU admission, all patients -5% ICU admission, within c.. 3% Hospitalization, all patients -22% Hospitalization, within c.. -13% Case -8% PPIs for COVID-19  Israelsen et al.  Prophylaxis Is prophylaxis with PPIs beneficial for COVID-19? Retrospective 322,975 patients in Denmark (February - December 2020) Higher hospitalization (p=0.005) and more cases (p=0.0012) c19early.org Israelsen et al., Clinical Gastroenter.., Sep 2021 FavorsPPI Favorscontrol 0 0.5 1 1.5 2+
PPIs for COVID-19
1st treatment shown to increase risk in September 2020, now with p = 0.00000012 from 39 studies.
5,100+ studies for 109 treatments. c19early.org
Retrospective 83,224 SARS-CoV-2 cases and 332,799 controls in Denmark showing increased risk of infection and hospital admission with proton pump inhibitor (PPI) use, but no significant association with ICU admission or mortality.
risk of death, 5.0% lower, RR 0.95, p = 0.70, treatment 166 of 3,955 (4.2%), control 189 of 3,955 (4.8%), NNT 172, adjusted per study, all patients, propensity score matching, multivariable.
risk of death, 12.0% lower, RR 0.88, p = 0.22, treatment 166 of 3,955 (4.2%), control 189 of 3,955 (4.8%), NNT 172, adjusted per study, within cases, propensity score matching, multivariable.
risk of mechanical ventilation, 8.0% higher, RR 1.08, p = 0.73, treatment 55 of 3,955 (1.4%), control 55 of 3,955 (1.4%), adjusted per study, all patients, propensity score matching, multivariable.
risk of mechanical ventilation, no change, RR 1.00, p = 1.00, treatment 55 of 3,955 (1.4%), control 55 of 3,955 (1.4%), adjusted per study, within cases, propensity score matching, multivariable.
risk of ICU admission, 4.8% higher, RR 1.05, p = 0.80, treatment 92 of 3,955 (2.3%), control 95 of 3,955 (2.4%), NNT 1318, adjusted per study, all patients, propensity score matching, multivariable.
risk of ICU admission, 3.0% lower, RR 0.97, p = 0.84, treatment 92 of 3,955 (2.3%), control 95 of 3,955 (2.4%), NNT 1318, adjusted per study, within cases, propensity score matching, multivariable.
risk of hospitalization, 22.0% higher, RR 1.22, p = 0.005, treatment 734 of 3,955 (18.6%), control 650 of 3,955 (16.4%), adjusted per study, all patients, propensity score matching, multivariable.
risk of hospitalization, 13.0% higher, RR 1.13, p = 0.010, treatment 734 of 3,955 (18.6%), control 650 of 3,955 (16.4%), adjusted per study, within cases, propensity score matching, multivariable.
risk of case, 8.0% higher, OR 1.08, p = 0.001, treatment 4,473 of 63,886 (7.0%) cases, 17,553 of 259,089 (6.8%) controls, adjusted per study, case control OR, current vs. non-use, multivariable.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Israelsen et al., 30 Sep 2021, retrospective, Denmark, peer-reviewed, 7 authors, study period 27 February, 2020 - 1 December, 2020, trial EUPAS35835.
This PaperPPIsAll
Proton Pump Inhibitor Use Is Not Strongly Associated With SARS-CoV-2 Related Outcomes: A Nationwide Study and Meta-analysis
Simone Bastrup Israelsen, Martin Thomsen Ernst, Andreas Lundh, Lene Fogt Lundbo, Håkon Sandholdt, Jesper Hallas, Thomas Benfield
Clinical Gastroenterology and Hepatology, doi:10.1016/j.cgh.2021.05.011
PPI use does not impact SARS-CoV-2 related outcomes No difference -Risk of infection -Severe outcomes
Supplementary Material Note: To access the supplementary material accompanying this article, visit the online version of Clinical Gastroenterology and Hepatology at www.cghjournal.org, and at https://doi.org/10.1016/j.cgh.2021.05.011. Conflicts of interest This author discloses the following: Thomas Benfield reports grants from Novo Nordisk Foundation, grants from Simonsen Foundation, grants and personal fees from GSK, grants and personal fees from Pfizer, personal fees from Boehringer Ingelheim, grants and personal fees from Gilead, personal fees from MSD, grants from Lundbeck Foundation, grants from Kai Hansen Foundation, and personal fees from Pentabase A/S, with no relation to the work reported in this article. The remaining authors disclose no conflicts. Adjusted for age, sex, comorbidities (peptic ulcer, asthma, chronic obstructive pulmonary disease, cirrhosis, ischemic heart disease, diabetes, renal failure, heart failure, stroke, alcohol-related diagnoses, smoking-related diagnoses, major psychiatric disorders), other current medication use (systemic and inhaled corticosteroids, bronchodilators, H2-receptor antagonists, nonsteroidal anti-inflammatory drugs, anticholinergic agents, immunosuppressants, antipsychotic agents, antibiotics, alcohol abstinence treatment, smoking cessation treatment, blood pressure lowering drugs, lipid lowering drugs, glucose lowering drugs, antiplatelets, anticoagulants), Charlson Comorbidity Index (0, 1-2, 3þ), and number of hospital..
References
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Zhou, Wang, Lee, Proton pump inhibitor or famotidine use and severe COVID-19 disease: a propensity scorematched territory-wide study, Gut
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