International cohort study indicates no association between alpha-1 blockers and susceptibility to COVID-19 in benign prostatic hyperplasia patients

Akihiko Nishimura; Junqing Xie; Kristin Kostka; Talita Duarte-Salles; Sergio Fernández Bertolín; María Aragón; Clair Blacketer; Azza Shoaibi; Scott L, DuVall; Kristine Lynch; Michael E. Matheny; Thomas Falconer; Daniel R. Morales; Mitchell M. Conover; Seng Chan You; Nicole Pratt; James Weaver; Anthony G. Sena; Martijn J. Schuemie; Jenna Reps; Christian Reich; Peter R. Rijnbeek; Patrick B. Ryan; George Hripcsak; Daniel Prieto-Alhambra; Marc A. Suchard

doi:10.3389/fphar.2022.945592

International cohort study indicates no association between alpha-1 blockers and susceptibility to COVID-19 in benign prostatic hyperplasia patients

Akihiko Nishimura, Junqing Xie, Kristin Kostka, Talita Duarte-Salles, Sergio Fernández Bertolín, María Aragón, Clair Blacketer, Azza Shoaibi, Scott L, DuVall, Kristine Lynch, Michael E. Matheny, Thomas Falconer, Daniel R. Morales, Mitchell M. Conover, Seng Chan You, Nicole Pratt, James Weaver, Anthony G. Sena, Martijn J. Schuemie, Jenna RepsChristian Reich, Peter R. Rijnbeek, Patrick B. Ryan, George Hripcsak, Daniel Prieto-Alhambra (Lead / Corresponding author), Marc A. Suchard

Population Health and Genomics

Research output: Contribution to journal › Article › peer-review

4 Citations (Scopus)

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Abstract

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.

Original language	English
Article number	945592
Number of pages	14
Journal	Frontiers in Pharmacology
Volume	13
DOIs	https://doi.org/10.3389/fphar.2022.945592
Publication status	Published - 14 Sept 2022

Keywords

treatment for SARS CoV-2
observational study
electronic health records
federated data model
causal inference
open science

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10.3389/fphar.2022.945592Licence: CC BY

Final published versionFinal published version, 1.79 MBLicence: CC BY

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Nishimura, A., Xie, J., Kostka, K., Duarte-Salles, T., Fernández Bertolín, S., Aragón, M., Blacketer, C., Shoaibi, A., DuVall, S. L., Lynch, K., Matheny, M. E., Falconer, T., Morales, D. R., Conover, M. M., Chan You, S., Pratt, N., Weaver, J., Sena, A. G., Schuemie, M. J., ... Suchard, M. A. (2022). International cohort study indicates no association between alpha-1 blockers and susceptibility to COVID-19 in benign prostatic hyperplasia patients. Frontiers in Pharmacology, 13, Article 945592. https://doi.org/10.3389/fphar.2022.945592

@article{d8d3f9b7087b4504987c54d5d0ea1383,

title = "International cohort study indicates no association between alpha-1 blockers and susceptibility to COVID-19 in benign prostatic hyperplasia patients",

abstract = "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.",

keywords = "treatment for SARS CoV-2, observational study, electronic health records, federated data model, causal inference, open science",

author = "Akihiko Nishimura and Junqing Xie and Kristin Kostka and Talita Duarte-Salles and {Fern{\'a}ndez Bertol{\'i}n}, Sergio and Mar{\'i}a Arag{\'o}n and Clair Blacketer and Azza Shoaibi and DuVall, {Scott L,} and Kristine Lynch and Matheny, {Michael E.} and Thomas Falconer and Morales, {Daniel R.} and Conover, {Mitchell M.} and {Chan You}, Seng and Nicole Pratt and James Weaver and Sena, {Anthony G.} and Schuemie, {Martijn J.} and Jenna Reps and Christian Reich and Rijnbeek, {Peter R.} and Ryan, {Patrick B.} and George Hripcsak and Daniel Prieto-Alhambra and Suchard, {Marc A.}",

note = "Funding Information: AN receives contract support from the US Food and Drug Administration (HHS-FDA 75F40120D00039) and also receives grant support from the National Institute of Health (R01 AG068002). JX receives scholarship from the Clarendon Fund and Jardine Foundation. KK and CR are employees of IQVIA. TD-S and DP-A received support for this project from the European Health Data and Evidence Network (EHDEN) project. EHDEN received funding from the Innovative Medicines Initiative 2 Joint Undertaking (JU) under grant agreement No 806968. The JU receives support from the European Union{\textquoteright}s Horizon 2020 research and innovation programme and EFPIA. This project is funded by the Health Department from the Generalitat de Catalunya with a grant for research projects on SARS-CoV-2 and COVID-19 disease organized by the Direcci{\'o} General de Recerca i Innovaci{\'o} en Salut. CB, AS, MC, JW, AS, MS, JR, and PR are employees of Janssen Research and Development. SD, KL, and MM are employees of the US Department of Veterans Affairs (VA) and report funding from the VA Informatics and Computing Infrastructure (VA HSR RES 13-457). SD reports research grants from the following for-profit organizations: AbbVie Inc., Alnylam Pharmaceuticals Inc., Astellas Pharma Inc., AstraZeneca Pharmaceuticals LP, Biodesix, Inc., Boehringer Ingelheim International GmbH, Celgene Corporation, Eli Lilly and Company, Genentech Inc., Gilead Sciences Inc., GlaxoSmithKline PLC, Innocrin Pharmaceuticals Inc., Janssen Pharmaceuticals, Inc., Kantar Health, Myriad Genetic Laboratories, Inc., Novartis International AG, and Parexel International Corporation through the University of Utah or Western Institute for Veteran Research outside the submitted work. DM is funded by a Wellcome Trust Clinical Research Career Development Fellowship (Grant 214588/Z/18/Z) and has received support from the National Institute for Health Research, Scottish Chief Scientist Office and Tenovus Scotland unrelated to this work. NP received grants from the Australian National Health and Medical Research Council GNT1157506. PR received support for this project from the EHDEN project. GH receives a grant for this work from the US National Institutes of Health (R01 LM006910). DP-A receives support from NIHR Senior Research Fellowship (SRF-2018-11-ST2-004), and from the Bill and Melinda Gates Foundation (INV016201). The University of Oxford also received partial support from the UK National Institute for Health Research (NIHR) Oxford Biomedical Research Centre. MS receives grants from the National Institutes of Health and IQVIA and contracts from the US Food and Drug Administration, US Department of Veterans Affairs, Janssen Research and Development and Private Health Management all outside the scope of this work. The views and opinions expressed are those of the authors and do not necessarily reflect those of the NIHR Academy programme, NIHR, Bill and Melinda Gates Foundation, US Department of Veterans Affairs, United States Government, NHS, National Institutes of Health or the Department of Health, England. Copyright Information: {\textcopyright} 2022 Nishimura, Xie, Kostka, Duarte-Salles, Fern{\'a}ndez Bertol{\'i}n, Arag{\'o}n, Blacketer, Shoaibi, DuVall, Lynch, Matheny, Falconer, Morales, Conover, Chan You, Pratt, Weaver, Sena, Schuemie, Reps, Reich, Rijnbeek, Ryan, Hripcsak, Prieto-Alhambra and Suchard.",

year = "2022",

month = sep,

day = "14",

doi = "10.3389/fphar.2022.945592",

language = "English",

volume = "13",

journal = "Frontiers in Pharmacology",

issn = "1663-9812",

publisher = "Frontiers Media",

}

Nishimura, A, Xie, J, Kostka, K, Duarte-Salles, T, Fernández Bertolín, S, Aragón, M, Blacketer, C, Shoaibi, A, DuVall, SL, Lynch, K, Matheny, ME, Falconer, T, Morales, DR, Conover, MM, Chan You, S, Pratt, N, Weaver, J, Sena, AG, Schuemie, MJ, Reps, J, Reich, C, Rijnbeek, PR, Ryan, PB, Hripcsak, G, Prieto-Alhambra, D & Suchard, MA 2022, 'International cohort study indicates no association between alpha-1 blockers and susceptibility to COVID-19 in benign prostatic hyperplasia patients', Frontiers in Pharmacology, vol. 13, 945592. https://doi.org/10.3389/fphar.2022.945592

TY - JOUR

T1 - International cohort study indicates no association between alpha-1 blockers and susceptibility to COVID-19 in benign prostatic hyperplasia patients

AU - Nishimura, Akihiko

AU - Xie, Junqing

AU - Kostka, Kristin

AU - Duarte-Salles, Talita

AU - Fernández Bertolín, Sergio

AU - Aragón, María

AU - Blacketer, Clair

AU - Shoaibi, Azza

AU - DuVall, Scott L,

AU - Lynch, Kristine

AU - Matheny, Michael E.

AU - Falconer, Thomas

AU - Morales, Daniel R.

AU - Conover, Mitchell M.

AU - Chan You, Seng

AU - Pratt, Nicole

AU - Weaver, James

AU - Sena, Anthony G.

AU - Schuemie, Martijn J.

AU - Reps, Jenna

AU - Reich, Christian

AU - Rijnbeek, Peter R.

AU - Ryan, Patrick B.

AU - Hripcsak, George

AU - Prieto-Alhambra, Daniel

AU - Suchard, Marc A.

N1 - Funding Information: AN receives contract support from the US Food and Drug Administration (HHS-FDA 75F40120D00039) and also receives grant support from the National Institute of Health (R01 AG068002). JX receives scholarship from the Clarendon Fund and Jardine Foundation. KK and CR are employees of IQVIA. TD-S and DP-A received support for this project from the European Health Data and Evidence Network (EHDEN) project. EHDEN received funding from the Innovative Medicines Initiative 2 Joint Undertaking (JU) under grant agreement No 806968. The JU receives support from the European Union’s Horizon 2020 research and innovation programme and EFPIA. This project is funded by the Health Department from the Generalitat de Catalunya with a grant for research projects on SARS-CoV-2 and COVID-19 disease organized by the Direcció General de Recerca i Innovació en Salut. CB, AS, MC, JW, AS, MS, JR, and PR are employees of Janssen Research and Development. SD, KL, and MM are employees of the US Department of Veterans Affairs (VA) and report funding from the VA Informatics and Computing Infrastructure (VA HSR RES 13-457). SD reports research grants from the following for-profit organizations: AbbVie Inc., Alnylam Pharmaceuticals Inc., Astellas Pharma Inc., AstraZeneca Pharmaceuticals LP, Biodesix, Inc., Boehringer Ingelheim International GmbH, Celgene Corporation, Eli Lilly and Company, Genentech Inc., Gilead Sciences Inc., GlaxoSmithKline PLC, Innocrin Pharmaceuticals Inc., Janssen Pharmaceuticals, Inc., Kantar Health, Myriad Genetic Laboratories, Inc., Novartis International AG, and Parexel International Corporation through the University of Utah or Western Institute for Veteran Research outside the submitted work. DM is funded by a Wellcome Trust Clinical Research Career Development Fellowship (Grant 214588/Z/18/Z) and has received support from the National Institute for Health Research, Scottish Chief Scientist Office and Tenovus Scotland unrelated to this work. NP received grants from the Australian National Health and Medical Research Council GNT1157506. PR received support for this project from the EHDEN project. GH receives a grant for this work from the US National Institutes of Health (R01 LM006910). DP-A receives support from NIHR Senior Research Fellowship (SRF-2018-11-ST2-004), and from the Bill and Melinda Gates Foundation (INV016201). The University of Oxford also received partial support from the UK National Institute for Health Research (NIHR) Oxford Biomedical Research Centre. MS receives grants from the National Institutes of Health and IQVIA and contracts from the US Food and Drug Administration, US Department of Veterans Affairs, Janssen Research and Development and Private Health Management all outside the scope of this work. The views and opinions expressed are those of the authors and do not necessarily reflect those of the NIHR Academy programme, NIHR, Bill and Melinda Gates Foundation, US Department of Veterans Affairs, United States Government, NHS, National Institutes of Health or the Department of Health, England. Copyright Information: © 2022 Nishimura, Xie, Kostka, Duarte-Salles, Fernández Bertolín, Aragón, Blacketer, Shoaibi, DuVall, Lynch, Matheny, Falconer, Morales, Conover, Chan You, Pratt, Weaver, Sena, Schuemie, Reps, Reich, Rijnbeek, Ryan, Hripcsak, Prieto-Alhambra and Suchard.

PY - 2022/9/14

Y1 - 2022/9/14

N2 - 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.

AB - 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.

KW - treatment for SARS CoV-2

KW - observational study

KW - electronic health records

KW - federated data model

KW - causal inference

KW - open science

UR - http://www.scopus.com/inward/record.url?scp=85138931864&partnerID=8YFLogxK

U2 - 10.3389/fphar.2022.945592

DO - 10.3389/fphar.2022.945592

M3 - Article

C2 - 36188566

SN - 1663-9812

VL - 13

JO - Frontiers in Pharmacology

JF - Frontiers in Pharmacology

M1 - 945592

ER -

International cohort study indicates no association between alpha-1 blockers and susceptibility to COVID-19 in benign prostatic hyperplasia patients

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Approaches for Creating Clinical Evidence of Treatment Effects in Routine Populations Excluded from Trials (ACCEPT) (Clinical Research Career Development Fellowship)

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International cohort study indicates no association between alpha-1 blockers and susceptibility to COVID-19 in benign prostatic hyperplasia patients

Abstract

Keywords

Access to Document

Other files and links

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Approaches for Creating Clinical Evidence of Treatment Effects in Routine Populations Excluded from Trials (ACCEPT) (Clinical Research Career Development Fellowship)

Cite this