Paul M McKeigue1,2, Sharon Kennedy3, Amanda Weir4, Jen Bishop4, Stuart J McGurnaghan5, David McAllister4,6, Chris Robertson4,7, Rachael Wood3, Nazir Lone8, Janet Murray4, Thomas M Caparrotta5, Alison Smith-Palmer4, David Goldberg4, Jim McMenamin4, Bruce Guthrie8, Sharon Hutchinson4,9, Helen M Colhoun4,5. 1. Usher Institute, College of Medicine and Veterinary Medicine, University of Edinburgh, Teviot Place, Edinburgh, EH8 9AG, Scotland. paul.mckeigue@ed.ac.uk. 2. Public Health Scotland, Meridian Court, 5 Cadogan Street, Glasgow, G2 6QE, Scotland. paul.mckeigue@ed.ac.uk. 3. NHS Information Services Division (Public Health Scotland), Gyle Square, 1 South Gyle Crescent, Edinburgh, EH12 9EB, Scotland. 4. Public Health Scotland, Meridian Court, 5 Cadogan Street, Glasgow, G2 6QE, Scotland. 5. Institute of Genetics and Molecular Medicine, College of Medicine and Veterinary Medicine, University of Edinburgh, Western General Hospital Campus, Crewe Road, Edinburgh, EH4 2XUC, Scotland. 6. Institute of Health and Wellbeing, University of Glasgow, 1 Lilybank Gardens, Glasgow, G12 8RZ, Scotland. 7. Department of Mathematics and Statistics, University of Strathclyde, 16 Richmond Street, Glasgow, G1 1XQ, Scotland. 8. Usher Institute, College of Medicine and Veterinary Medicine, University of Edinburgh, Teviot Place, Edinburgh, EH8 9AG, Scotland. 9. School of Health and Life Sciences, Glasgow Caledonian University, Glasgow, Scotland.
Abstract
BACKGROUND: The objective of this study was to investigate the relation of severe COVID-19 to prior drug prescribing. METHODS: Severe cases were defined by entry to critical care or fatal outcome. For this matched case-control study (REACT-SCOT), all 4251 cases of severe COVID-19 in Scotland since the start of the epidemic were matched for age, sex and primary care practice to 36,738 controls from the population register. Records were linked to hospital discharges since June 2015 and dispensed prescriptions issued in primary care during the last 240 days. RESULTS: Severe COVID-19 was strongly associated with the number of non-cardiovascular drug classes dispensed. This association was strongest in those not resident in a care home, in whom the rate ratio (95% CI) associated with dispensing of 12 or more drug classes versus none was 10.8 (8.8, 13.3), and in those without any of the conditions designated as conferring increased risk of COVID-19. Of 17 drug classes postulated at the start of the epidemic to be "medications compromising COVID", all were associated with increased risk of severe COVID-19 and these associations were present in those without any of the designated risk conditions. The fraction of cases in the population attributable to exposure to these drug classes was 38%. The largest effect was for antipsychotic agents: rate ratio 4.18 (3.42, 5.11). Other drug classes with large effects included proton pump inhibitors (rate ratio 2.20 (1.72, 2.83) for = 2 defined daily doses/day), opioids (3.66 (2.68, 5.01) for = 50 mg morphine equivalent/day) and gabapentinoids. These associations persisted after adjusting for covariates and were stronger with recent than with non-recent exposure. CONCLUSIONS: Severe COVID-19 is associated with polypharmacy and with drugs that cause sedation, respiratory depression, or dyskinesia; have anticholinergic effects; or affect the gastrointestinal system. These associations are not easily explained by co-morbidity. Measures to reduce the burden of mortality and morbidity from COVID-19 should include reinforcing existing guidance on reducing overprescribing of these drug classes and limiting inappropriate polypharmacy. REGISTRATION: ENCEPP number EUPAS35558.
BACKGROUND: The objective of this study was to investigate the relation of severe COVID-19 to prior drug prescribing. METHODS: Severe cases were defined by entry to critical care or fatal outcome. For this matched case-control study (REACT-SCOT), all 4251 cases of severe COVID-19 in Scotland since the start of the epidemic were matched for age, sex and primary care practice to 36,738 controls from the population register. Records were linked to hospital discharges since June 2015 and dispensed prescriptions issued in primary care during the last 240 days. RESULTS: Severe COVID-19 was strongly associated with the number of non-cardiovascular drug classes dispensed. This association was strongest in those not resident in a care home, in whom the rate ratio (95% CI) associated with dispensing of 12 or more drug classes versus none was 10.8 (8.8, 13.3), and in those without any of the conditions designated as conferring increased risk of COVID-19. Of 17 drug classes postulated at the start of the epidemic to be "medications compromising COVID", all were associated with increased risk of severe COVID-19 and these associations were present in those without any of the designated risk conditions. The fraction of cases in the population attributable to exposure to these drug classes was 38%. The largest effect was for antipsychotic agents: rate ratio 4.18 (3.42, 5.11). Other drug classes with large effects included proton pump inhibitors (rate ratio 2.20 (1.72, 2.83) for = 2 defined daily doses/day), opioids (3.66 (2.68, 5.01) for = 50 mg morphine equivalent/day) and gabapentinoids. These associations persisted after adjusting for covariates and were stronger with recent than with non-recent exposure. CONCLUSIONS: Severe COVID-19 is associated with polypharmacy and with drugs that cause sedation, respiratory depression, or dyskinesia; have anticholinergic effects; or affect the gastrointestinal system. These associations are not easily explained by co-morbidity. Measures to reduce the burden of mortality and morbidity from COVID-19 should include reinforcing existing guidance on reducing overprescribing of these drug classes and limiting inappropriate polypharmacy. REGISTRATION: ENCEPP number EUPAS35558.
Authors: Paul M McKeigue; David A McAllister; Sharon J Hutchinson; Chris Robertson; Diane Stockton; Helen M Colhoun Journal: Lancet Respir Med Date: 2022-02-25 Impact factor: 102.642