Frontiers in Pharmacology (Sep 2022)
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,
- 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
Affiliations
- Akihiko Nishimura
- Department of Biostatistics, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, United States
- Junqing Xie
- Centre for Statistics in Medicine, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Oxford University, Oxford, United Kingdom
- Kristin Kostka
- Real World Solutions, IQVIA, Cambridge, MA, United States
- Kristin Kostka
- The OHDSI Center at The Roux Institute, Northeastern University, Portland, ME, United States
- Talita Duarte-Salles
- Fundació Institut Universitari Per a la Recerca a l'Atenció Primària de Salut Jordi Gol i Gurina (IDIAPJGol), Barcelona, Spain
- Sergio Fernández Bertolín
- Fundació Institut Universitari Per a la Recerca a l'Atenció Primària de Salut Jordi Gol i Gurina (IDIAPJGol), Barcelona, Spain
- María Aragón
- Fundació Institut Universitari Per a la Recerca a l'Atenció Primària de Salut Jordi Gol i Gurina (IDIAPJGol), Barcelona, Spain
- Clair Blacketer
- Observational Health Data Analytics, Janssen Research and Development, Titusville, NJ, United States
- Azza Shoaibi
- Observational Health Data Analytics, Janssen Research and Development, Titusville, NJ, United States
- Scott L. DuVall
- VA Informatics and Computing Infrastructure, VA Salt Lake City Health Care System, Salt Lake City, UT, United States
- Scott L. DuVall
- Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, UT, United States
- Kristine Lynch
- VA Informatics and Computing Infrastructure, VA Salt Lake City Health Care System, Salt Lake City, UT, United States
- Kristine Lynch
- Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, UT, United States
- Michael E. Matheny
- Tennessee Valley Healthcare System, Veterans Affairs Medical Center, Nashville, TN, United States
- Michael E. Matheny
- 0Department of Biomedical Informatics, Vanderbilt University Medical Center, Nashville, TN, United States
- Thomas Falconer
- 1Department of Biomedical Informatics, Columbia University, New York, NY, United States
- Daniel R. Morales
- 2Division of Population Health and Genomics, University of Dundee, Dundee, United Kingdom
- Daniel R. Morales
- 3Department of Public Health, University of Southern Denmark, Southern Denmark, Denmark
- Mitchell M. Conover
- Observational Health Data Analytics, Janssen Research and Development, Titusville, NJ, United States
- Seng Chan You
- 4Department of Preventive Medicine and Public Health, Yonsei University College of Medicine, Seoul, South Korea
- Nicole Pratt
- 5Quality Use of Medicines and Pharmacy Research Centre, Clinical and Health Sciences, University of South Australia, Adelaide, Australia
- James Weaver
- Observational Health Data Analytics, Janssen Research and Development, Titusville, NJ, United States
- Anthony G. Sena
- Observational Health Data Analytics, Janssen Research and Development, Titusville, NJ, United States
- Anthony G. Sena
- 6Department of Medical Informatics, Erasmus University Medical Center, Rotterdam, Netherlands
- Martijn J. Schuemie
- Observational Health Data Analytics, Janssen Research and Development, Titusville, NJ, United States
- Martijn J. Schuemie
- 7Department of Biostatistics, UCLA Fielding School of Public Health, University of California, Los Angeles, Los Angeles, CA, United States
- Jenna Reps
- Observational Health Data Analytics, Janssen Research and Development, Titusville, NJ, United States
- Christian Reich
- Real World Solutions, IQVIA, Cambridge, MA, United States
- Peter R. Rijnbeek
- 6Department of Medical Informatics, Erasmus University Medical Center, Rotterdam, Netherlands
- Patrick B. Ryan
- Observational Health Data Analytics, Janssen Research and Development, Titusville, NJ, United States
- George Hripcsak
- 1Department of Biomedical Informatics, Columbia University, New York, NY, United States
- Daniel Prieto-Alhambra
- Centre for Statistics in Medicine, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Oxford University, Oxford, United Kingdom
- Marc A. Suchard
- 7Department of Biostatistics, UCLA Fielding School of Public Health, University of California, Los Angeles, Los Angeles, CA, United States
- Marc A. Suchard
- 8Department of Computational Medicine, David Geffen School of Medicine at UCLA, University of California, Los Angeles, Los Angeles, CA, United States
- Marc A. Suchard
- 9Department of Human Genetics, David Geffen School of Medicine at UCLA, University of California, Los Angeles, Los Angeles, CA, United States
- DOI
- https://doi.org/10.3389/fphar.2022.945592
- Journal volume & issue
-
Vol. 13
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