International cohort study indicates no association between alpha-1 blockers and susceptibility to COVID-19 in benign prostatic hyperplasia patients
Purpose: Alpha-1 blockers, often used to treat benign prostatic hyperplasia (BPH), have been hypothesized to prevent COVID-19 complications by minimising cytokine storm release. The proposed treatment based on this hypothesis currently lacks support from reliable real-world evidence, however. We lev...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2022-09-01
|
| Series: | Frontiers in Pharmacology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2022.945592/full |
| _version_ | 1828404889804341248 |
|---|---|
| author | Akihiko Nishimura Junqing Xie Kristin Kostka Kristin Kostka Talita Duarte-Salles Sergio Fernández Bertolín María Aragón Clair Blacketer Azza Shoaibi Scott L. DuVall Scott L. DuVall Kristine Lynch Kristine Lynch Michael E. Matheny Michael E. Matheny Thomas Falconer Daniel R. Morales Daniel R. Morales Mitchell M. Conover Seng Chan You Nicole Pratt James Weaver Anthony G. Sena Anthony G. Sena Martijn J. Schuemie Martijn J. Schuemie Jenna Reps Christian Reich Peter R. Rijnbeek Patrick B. Ryan George Hripcsak Daniel Prieto-Alhambra Marc A. Suchard Marc A. Suchard Marc A. Suchard |
| author_facet | Akihiko Nishimura Junqing Xie Kristin Kostka Kristin Kostka Talita Duarte-Salles Sergio Fernández Bertolín María Aragón Clair Blacketer Azza Shoaibi Scott L. DuVall Scott L. DuVall Kristine Lynch Kristine Lynch Michael E. Matheny Michael E. Matheny Thomas Falconer Daniel R. Morales Daniel R. Morales Mitchell M. Conover Seng Chan You Nicole Pratt James Weaver Anthony G. Sena Anthony G. Sena Martijn J. Schuemie Martijn J. Schuemie Jenna Reps Christian Reich Peter R. Rijnbeek Patrick B. Ryan George Hripcsak Daniel Prieto-Alhambra Marc A. Suchard Marc A. Suchard Marc A. Suchard |
| author_sort | Akihiko Nishimura |
| collection | DOAJ |
| description | Purpose: Alpha-1 blockers, often used to treat benign prostatic hyperplasia (BPH), have been hypothesized to prevent COVID-19 complications by minimising cytokine storm release. The proposed treatment based on this hypothesis currently lacks support from reliable real-world evidence, however. We leverage an international network of large-scale healthcare databases to generate comprehensive evidence in a transparent and reproducible manner.Methods: In this international cohort study, we deployed electronic health records from Spain (SIDIAP) and the United States (Department of Veterans Affairs, Columbia University Irving Medical Center, IQVIA OpenClaims, Optum DOD, Optum EHR). We assessed association between alpha-1 blocker use and risks of three COVID-19 outcomes—diagnosis, hospitalization, and hospitalization requiring intensive services—using a prevalent-user active-comparator design. We estimated hazard ratios using state-of-the-art techniques to minimize potential confounding, including large-scale propensity score matching/stratification and negative control calibration. We pooled database-specific estimates through random effects meta-analysis.Results: Our study overall included 2.6 and 0.46 million users of alpha-1 blockers and of alternative BPH medications. We observed no significant difference in their risks for any of the COVID-19 outcomes, with our meta-analytic HR estimates being 1.02 (95% CI: 0.92–1.13) for diagnosis, 1.00 (95% CI: 0.89–1.13) for hospitalization, and 1.15 (95% CI: 0.71–1.88) for hospitalization requiring intensive services.Conclusion: We found no evidence of the hypothesized reduction in risks of the COVID-19 outcomes from the prevalent-use of alpha-1 blockers—further research is needed to identify effective therapies for this novel disease. |
| first_indexed | 2024-12-10T10:43:45Z |
| format | Article |
| id | doaj.art-76b6ba2dc8174d1a836be00e2db65f87 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-12-10T10:43:45Z |
| publishDate | 2022-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-76b6ba2dc8174d1a836be00e2db65f872022-12-22T01:52:13ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122022-09-011310.3389/fphar.2022.945592945592International cohort study indicates no association between alpha-1 blockers and susceptibility to COVID-19 in benign prostatic hyperplasia patientsAkihiko Nishimura0Junqing Xie1Kristin Kostka2Kristin Kostka3Talita Duarte-Salles4Sergio Fernández Bertolín5María Aragón6Clair Blacketer7Azza Shoaibi8Scott L. DuVall9Scott L. DuVall10Kristine Lynch11Kristine Lynch12Michael E. Matheny13Michael E. Matheny14Thomas Falconer15Daniel R. Morales16Daniel R. Morales17Mitchell M. Conover18Seng Chan You19Nicole Pratt20James Weaver21Anthony G. Sena22Anthony G. Sena23Martijn J. Schuemie24Martijn J. Schuemie25Jenna Reps26Christian Reich27Peter R. Rijnbeek28Patrick B. Ryan29George Hripcsak30Daniel Prieto-Alhambra31Marc A. Suchard32Marc A. Suchard33Marc A. Suchard34Department of Biostatistics, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, United StatesCentre for Statistics in Medicine, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Oxford University, Oxford, United KingdomReal World Solutions, IQVIA, Cambridge, MA, United StatesThe OHDSI Center at The Roux Institute, Northeastern University, Portland, ME, United StatesFundació Institut Universitari Per a la Recerca a l'Atenció Primària de Salut Jordi Gol i Gurina (IDIAPJGol), Barcelona, SpainFundació Institut Universitari Per a la Recerca a l'Atenció Primària de Salut Jordi Gol i Gurina (IDIAPJGol), Barcelona, SpainFundació Institut Universitari Per a la Recerca a l'Atenció Primària de Salut Jordi Gol i Gurina (IDIAPJGol), Barcelona, SpainObservational Health Data Analytics, Janssen Research and Development, Titusville, NJ, United StatesObservational Health Data Analytics, Janssen Research and Development, Titusville, NJ, United StatesVA Informatics and Computing Infrastructure, VA Salt Lake City Health Care System, Salt Lake City, UT, United StatesDepartment of Internal Medicine, University of Utah School of Medicine, Salt Lake City, UT, United StatesVA Informatics and Computing Infrastructure, VA Salt Lake City Health Care System, Salt Lake City, UT, United StatesDepartment of Internal Medicine, University of Utah School of Medicine, Salt Lake City, UT, United StatesTennessee Valley Healthcare System, Veterans Affairs Medical Center, Nashville, TN, United States0Department of Biomedical Informatics, Vanderbilt University Medical Center, Nashville, TN, United States1Department of Biomedical Informatics, Columbia University, New York, NY, United States2Division of Population Health and Genomics, University of Dundee, Dundee, United Kingdom3Department of Public Health, University of Southern Denmark, Southern Denmark, DenmarkObservational Health Data Analytics, Janssen Research and Development, Titusville, NJ, United States4Department of Preventive Medicine and Public Health, Yonsei University College of Medicine, Seoul, South Korea5Quality Use of Medicines and Pharmacy Research Centre, Clinical and Health Sciences, University of South Australia, Adelaide, AustraliaObservational Health Data Analytics, Janssen Research and Development, Titusville, NJ, United StatesObservational Health Data Analytics, Janssen Research and Development, Titusville, NJ, United States6Department of Medical Informatics, Erasmus University Medical Center, Rotterdam, NetherlandsObservational Health Data Analytics, Janssen Research and Development, Titusville, NJ, United States7Department of Biostatistics, UCLA Fielding School of Public Health, University of California, Los Angeles, Los Angeles, CA, United StatesObservational Health Data Analytics, Janssen Research and Development, Titusville, NJ, United StatesReal World Solutions, IQVIA, Cambridge, MA, United States6Department of Medical Informatics, Erasmus University Medical Center, Rotterdam, NetherlandsObservational Health Data Analytics, Janssen Research and Development, Titusville, NJ, United States1Department of Biomedical Informatics, Columbia University, New York, NY, United StatesCentre for Statistics in Medicine, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Oxford University, Oxford, United Kingdom7Department of Biostatistics, UCLA Fielding School of Public Health, University of California, Los Angeles, Los Angeles, CA, United States8Department of Computational Medicine, David Geffen School of Medicine at UCLA, University of California, Los Angeles, Los Angeles, CA, United States9Department of Human Genetics, David Geffen School of Medicine at UCLA, University of California, Los Angeles, Los Angeles, CA, United StatesPurpose: Alpha-1 blockers, often used to treat benign prostatic hyperplasia (BPH), have been hypothesized to prevent COVID-19 complications by minimising cytokine storm release. The proposed treatment based on this hypothesis currently lacks support from reliable real-world evidence, however. We leverage an international network of large-scale healthcare databases to generate comprehensive evidence in a transparent and reproducible manner.Methods: In this international cohort study, we deployed electronic health records from Spain (SIDIAP) and the United States (Department of Veterans Affairs, Columbia University Irving Medical Center, IQVIA OpenClaims, Optum DOD, Optum EHR). We assessed association between alpha-1 blocker use and risks of three COVID-19 outcomes—diagnosis, hospitalization, and hospitalization requiring intensive services—using a prevalent-user active-comparator design. We estimated hazard ratios using state-of-the-art techniques to minimize potential confounding, including large-scale propensity score matching/stratification and negative control calibration. We pooled database-specific estimates through random effects meta-analysis.Results: Our study overall included 2.6 and 0.46 million users of alpha-1 blockers and of alternative BPH medications. We observed no significant difference in their risks for any of the COVID-19 outcomes, with our meta-analytic HR estimates being 1.02 (95% CI: 0.92–1.13) for diagnosis, 1.00 (95% CI: 0.89–1.13) for hospitalization, and 1.15 (95% CI: 0.71–1.88) for hospitalization requiring intensive services.Conclusion: We found no evidence of the hypothesized reduction in risks of the COVID-19 outcomes from the prevalent-use of alpha-1 blockers—further research is needed to identify effective therapies for this novel disease.https://www.frontiersin.org/articles/10.3389/fphar.2022.945592/fulltreatment for SARS CoV-2observational studyelectronic health recordsfederated data modelcausal inferenceopen science |
| spellingShingle | Akihiko Nishimura Junqing Xie Kristin Kostka Kristin Kostka Talita Duarte-Salles Sergio Fernández Bertolín María Aragón Clair Blacketer Azza Shoaibi Scott L. DuVall Scott L. DuVall Kristine Lynch Kristine Lynch Michael E. Matheny Michael E. Matheny Thomas Falconer Daniel R. Morales Daniel R. Morales Mitchell M. Conover Seng Chan You Nicole Pratt James Weaver Anthony G. Sena Anthony G. Sena Martijn J. Schuemie Martijn J. Schuemie Jenna Reps Christian Reich Peter R. Rijnbeek Patrick B. Ryan George Hripcsak Daniel Prieto-Alhambra Marc A. Suchard Marc A. Suchard Marc A. Suchard International cohort study indicates no association between alpha-1 blockers and susceptibility to COVID-19 in benign prostatic hyperplasia patients Frontiers in Pharmacology treatment for SARS CoV-2 observational study electronic health records federated data model causal inference open science |
| title | International cohort study indicates no association between alpha-1 blockers and susceptibility to COVID-19 in benign prostatic hyperplasia patients |
| title_full | International cohort study indicates no association between alpha-1 blockers and susceptibility to COVID-19 in benign prostatic hyperplasia patients |
| title_fullStr | International cohort study indicates no association between alpha-1 blockers and susceptibility to COVID-19 in benign prostatic hyperplasia patients |
| title_full_unstemmed | International cohort study indicates no association between alpha-1 blockers and susceptibility to COVID-19 in benign prostatic hyperplasia patients |
| title_short | International cohort study indicates no association between alpha-1 blockers and susceptibility to COVID-19 in benign prostatic hyperplasia patients |
| title_sort | international cohort study indicates no association between alpha 1 blockers and susceptibility to covid 19 in benign prostatic hyperplasia patients |
| topic | treatment for SARS CoV-2 observational study electronic health records federated data model causal inference open science |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2022.945592/full |
| work_keys_str_mv | AT akihikonishimura internationalcohortstudyindicatesnoassociationbetweenalpha1blockersandsusceptibilitytocovid19inbenignprostatichyperplasiapatients AT junqingxie internationalcohortstudyindicatesnoassociationbetweenalpha1blockersandsusceptibilitytocovid19inbenignprostatichyperplasiapatients AT kristinkostka internationalcohortstudyindicatesnoassociationbetweenalpha1blockersandsusceptibilitytocovid19inbenignprostatichyperplasiapatients AT kristinkostka internationalcohortstudyindicatesnoassociationbetweenalpha1blockersandsusceptibilitytocovid19inbenignprostatichyperplasiapatients AT talitaduartesalles internationalcohortstudyindicatesnoassociationbetweenalpha1blockersandsusceptibilitytocovid19inbenignprostatichyperplasiapatients AT sergiofernandezbertolin internationalcohortstudyindicatesnoassociationbetweenalpha1blockersandsusceptibilitytocovid19inbenignprostatichyperplasiapatients AT mariaaragon internationalcohortstudyindicatesnoassociationbetweenalpha1blockersandsusceptibilitytocovid19inbenignprostatichyperplasiapatients AT clairblacketer internationalcohortstudyindicatesnoassociationbetweenalpha1blockersandsusceptibilitytocovid19inbenignprostatichyperplasiapatients AT azzashoaibi internationalcohortstudyindicatesnoassociationbetweenalpha1blockersandsusceptibilitytocovid19inbenignprostatichyperplasiapatients AT scottlduvall internationalcohortstudyindicatesnoassociationbetweenalpha1blockersandsusceptibilitytocovid19inbenignprostatichyperplasiapatients AT scottlduvall internationalcohortstudyindicatesnoassociationbetweenalpha1blockersandsusceptibilitytocovid19inbenignprostatichyperplasiapatients AT kristinelynch internationalcohortstudyindicatesnoassociationbetweenalpha1blockersandsusceptibilitytocovid19inbenignprostatichyperplasiapatients AT kristinelynch internationalcohortstudyindicatesnoassociationbetweenalpha1blockersandsusceptibilitytocovid19inbenignprostatichyperplasiapatients AT michaelematheny internationalcohortstudyindicatesnoassociationbetweenalpha1blockersandsusceptibilitytocovid19inbenignprostatichyperplasiapatients AT michaelematheny internationalcohortstudyindicatesnoassociationbetweenalpha1blockersandsusceptibilitytocovid19inbenignprostatichyperplasiapatients AT thomasfalconer internationalcohortstudyindicatesnoassociationbetweenalpha1blockersandsusceptibilitytocovid19inbenignprostatichyperplasiapatients AT danielrmorales internationalcohortstudyindicatesnoassociationbetweenalpha1blockersandsusceptibilitytocovid19inbenignprostatichyperplasiapatients AT danielrmorales internationalcohortstudyindicatesnoassociationbetweenalpha1blockersandsusceptibilitytocovid19inbenignprostatichyperplasiapatients AT mitchellmconover internationalcohortstudyindicatesnoassociationbetweenalpha1blockersandsusceptibilitytocovid19inbenignprostatichyperplasiapatients AT sengchanyou internationalcohortstudyindicatesnoassociationbetweenalpha1blockersandsusceptibilitytocovid19inbenignprostatichyperplasiapatients AT nicolepratt internationalcohortstudyindicatesnoassociationbetweenalpha1blockersandsusceptibilitytocovid19inbenignprostatichyperplasiapatients AT jamesweaver internationalcohortstudyindicatesnoassociationbetweenalpha1blockersandsusceptibilitytocovid19inbenignprostatichyperplasiapatients AT anthonygsena internationalcohortstudyindicatesnoassociationbetweenalpha1blockersandsusceptibilitytocovid19inbenignprostatichyperplasiapatients AT anthonygsena internationalcohortstudyindicatesnoassociationbetweenalpha1blockersandsusceptibilitytocovid19inbenignprostatichyperplasiapatients AT martijnjschuemie internationalcohortstudyindicatesnoassociationbetweenalpha1blockersandsusceptibilitytocovid19inbenignprostatichyperplasiapatients AT martijnjschuemie internationalcohortstudyindicatesnoassociationbetweenalpha1blockersandsusceptibilitytocovid19inbenignprostatichyperplasiapatients AT jennareps internationalcohortstudyindicatesnoassociationbetweenalpha1blockersandsusceptibilitytocovid19inbenignprostatichyperplasiapatients AT christianreich internationalcohortstudyindicatesnoassociationbetweenalpha1blockersandsusceptibilitytocovid19inbenignprostatichyperplasiapatients AT peterrrijnbeek internationalcohortstudyindicatesnoassociationbetweenalpha1blockersandsusceptibilitytocovid19inbenignprostatichyperplasiapatients AT patrickbryan internationalcohortstudyindicatesnoassociationbetweenalpha1blockersandsusceptibilitytocovid19inbenignprostatichyperplasiapatients AT georgehripcsak internationalcohortstudyindicatesnoassociationbetweenalpha1blockersandsusceptibilitytocovid19inbenignprostatichyperplasiapatients AT danielprietoalhambra internationalcohortstudyindicatesnoassociationbetweenalpha1blockersandsusceptibilitytocovid19inbenignprostatichyperplasiapatients AT marcasuchard internationalcohortstudyindicatesnoassociationbetweenalpha1blockersandsusceptibilitytocovid19inbenignprostatichyperplasiapatients AT marcasuchard internationalcohortstudyindicatesnoassociationbetweenalpha1blockersandsusceptibilitytocovid19inbenignprostatichyperplasiapatients AT marcasuchard internationalcohortstudyindicatesnoassociationbetweenalpha1blockersandsusceptibilitytocovid19inbenignprostatichyperplasiapatients |