Metoprolol for the Prevention of Acute Exacerbations of COPD
Mark T Dransfield, Helen Voelker, Surya P Bhatt, Keith Brenner, Richard Casaburi, Carolyn E Come, J Allen D Cooper, Gerard J Criner, Jeffrey L Curtis, MeiLan K Han, Umur Hatipoğlu, Erika S Helgeson, Vipul V Jain, Ravi Kalhan, David Kaminsky, Robert Kaner, Ken M Kunisaki, Allison A Lambert, Matthew R Lammi, Sarah Lindberg, Barry J Make, Fernando J Martinez, Charlene McEvoy, Ralph J Panos, Robert M Reed, Paul D Scanlon, Frank C Sciurba, Anthony Smith, Peruvemba S Sriram, William W Stringer, Jeremy A Weingarten, J Michael Wells, Elizabeth Westfall, Stephen C Lazarus, John E Connett, BLOCK COPD Trial Group, Allen Cooper, Patti Smith, Carolyn E Come, Christina M Mercugliano, Erick S MacLean, Emily A Holmes, Kevin M Zinchuk, Ralph Panos, Kimberly Kersey, Laura Lach, Umur Hatipoglu, Amy Attaway, Anu Suri, Mohammed Al-Jaghbeer, Sudhir Dudekonda, Muhammad Raza, Richard Rice, Jenna Brinker, Keith Brenner, Immani Easthausen, M Atif Choudhury, Maahika Srinivasan, Sana Sajjad, Onumara Opara, Charlene E McEvoy, Pamela J Neuenfeldt, Cheryl Sasse, W Stringer, R Casaburi, H Rossiter, J Porszasz, L Diaz, R Indelicato, C Lopez-Garcia, R Calmelat, D Cavanaugh, Matthew R Lammi, Connie Romaine, Marie Sandi, Paula Lauto, Paul D Scanlon, Jeremy Clain, Alexander Niven, Megan Dulohery Scrodin, Boleyn Andrist, Alana English, Tami S Krpata, Ken Kunisaki, Megan Campbell, Miranda DeConcini, Anne Melzer, Chris Wendt, Erin Wetherbee, Doug DeCarolis, Barry Make, Steven Lommatzsch, Amen Sergew, Jennifer Underwood, Robert J Kaner, Fernando J Martinez, Ben-Gary Harvey, Daniel Libby, Laura Libby, Brian Gelbman, David Chappell Weir, Andrea Shioleno, Jamuna Krishnan, William Zhengyang Zhang, Elizabeth Peters, Alicia J Morris, Matthew Marcelino, Jeremy Weingarten, Anthony Saleh, Saleem Shahzad, Liziamma George, Liam Gross, Puja Chadha, Christina Edwards, Anthony Smith, Susan Ingenito, Ravi Kalhan, Sharon Rosenberg, Lewis Smith, Jenny Hixon, Allison Rogowski, Alyssa Frederick, Allison A Lambert, Radica Alicic, Thomas DeCato, Lisa Davis, David Lebo, Michael Jacobs, Gerard Criner, Nathaniel Marchetti, Helga Criner, Dee Fehrle, Joseph Lambert, Mark Dransfield, Surya Bhatt, J Michael Wells, Anand Iyer, Trisha Parekh, Steven Lloyd, Gregory Payne, Samuel McElwee, Elizabeth Westfall, Keenya Mathews, Renita Holmes, Vipul Jain, Dennis Richard Allison, John McClain, Janna Blaauw, Griselda Aguilar, Alexa Lopez, Stephen C Lazarus, Prescott G Woodruff, Julian Silva, Robert Reed, Giora Netzer, Archana Patel, Maura Deeley, Saif M Borgan, Sadam Haddadin, Hasan Radhi, Hassan A Haji, Nirali Marvania, MeiLan K Han, Wassim Labaki, Mary Kay Hamby, John E Connett, Chris Wendt, Sarah Lindberg, Helen Voelker, Irene Olson, Frank Sciurba, Divay Chandra, Jessica Bon Field, Michael Emmet O'Brien, Craig Riley, Paula Consolaro, Megan D'Innocenzo, Kelsey Elliott, Christina Ledezma, Jenna Smith, Elizabeth Stempkowski, Daniel Arminavage, Robert Wilson, Rhonda Lincoln, David A Kaminsky, Erika Gonyaw, Chloe Housenger, Kevin Hodgdon, Heidi Pecott-Grimm, Jeffrey L Curtis, Lisa McCloskey, Nadia Hansel, Vera Bittner, James Tonascia, Sandy Snyder, Usamah Kayyali, Mark T Dransfield, Helen Voelker, Surya P Bhatt, Keith Brenner, Richard Casaburi, Carolyn E Come, J Allen D Cooper, Gerard J Criner, Jeffrey L Curtis, MeiLan K Han, Umur Hatipoğlu, Erika S Helgeson, Vipul V Jain, Ravi Kalhan, David Kaminsky, Robert Kaner, Ken M Kunisaki, Allison A Lambert, Matthew R Lammi, Sarah Lindberg, Barry J Make, Fernando J Martinez, Charlene McEvoy, Ralph J Panos, Robert M Reed, Paul D Scanlon, Frank C Sciurba, Anthony Smith, Peruvemba S Sriram, William W Stringer, Jeremy A Weingarten, J Michael Wells, Elizabeth Westfall, Stephen C Lazarus, John E Connett, BLOCK COPD Trial Group, Allen Cooper, Patti Smith, Carolyn E Come, Christina M Mercugliano, Erick S MacLean, Emily A Holmes, Kevin M Zinchuk, Ralph Panos, Kimberly Kersey, Laura Lach, Umur Hatipoglu, Amy Attaway, Anu Suri, Mohammed Al-Jaghbeer, Sudhir Dudekonda, Muhammad Raza, Richard Rice, Jenna Brinker, Keith Brenner, Immani Easthausen, M Atif Choudhury, Maahika Srinivasan, Sana Sajjad, Onumara Opara, Charlene E McEvoy, Pamela J Neuenfeldt, Cheryl Sasse, W Stringer, R Casaburi, H Rossiter, J Porszasz, L Diaz, R Indelicato, C Lopez-Garcia, R Calmelat, D Cavanaugh, Matthew R Lammi, Connie Romaine, Marie Sandi, Paula Lauto, Paul D Scanlon, Jeremy Clain, Alexander Niven, Megan Dulohery Scrodin, Boleyn Andrist, Alana English, Tami S Krpata, Ken Kunisaki, Megan Campbell, Miranda DeConcini, Anne Melzer, Chris Wendt, Erin Wetherbee, Doug DeCarolis, Barry Make, Steven Lommatzsch, Amen Sergew, Jennifer Underwood, Robert J Kaner, Fernando J Martinez, Ben-Gary Harvey, Daniel Libby, Laura Libby, Brian Gelbman, David Chappell Weir, Andrea Shioleno, Jamuna Krishnan, William Zhengyang Zhang, Elizabeth Peters, Alicia J Morris, Matthew Marcelino, Jeremy Weingarten, Anthony Saleh, Saleem Shahzad, Liziamma George, Liam Gross, Puja Chadha, Christina Edwards, Anthony Smith, Susan Ingenito, Ravi Kalhan, Sharon Rosenberg, Lewis Smith, Jenny Hixon, Allison Rogowski, Alyssa Frederick, Allison A Lambert, Radica Alicic, Thomas DeCato, Lisa Davis, David Lebo, Michael Jacobs, Gerard Criner, Nathaniel Marchetti, Helga Criner, Dee Fehrle, Joseph Lambert, Mark Dransfield, Surya Bhatt, J Michael Wells, Anand Iyer, Trisha Parekh, Steven Lloyd, Gregory Payne, Samuel McElwee, Elizabeth Westfall, Keenya Mathews, Renita Holmes, Vipul Jain, Dennis Richard Allison, John McClain, Janna Blaauw, Griselda Aguilar, Alexa Lopez, Stephen C Lazarus, Prescott G Woodruff, Julian Silva, Robert Reed, Giora Netzer, Archana Patel, Maura Deeley, Saif M Borgan, Sadam Haddadin, Hasan Radhi, Hassan A Haji, Nirali Marvania, MeiLan K Han, Wassim Labaki, Mary Kay Hamby, John E Connett, Chris Wendt, Sarah Lindberg, Helen Voelker, Irene Olson, Frank Sciurba, Divay Chandra, Jessica Bon Field, Michael Emmet O'Brien, Craig Riley, Paula Consolaro, Megan D'Innocenzo, Kelsey Elliott, Christina Ledezma, Jenna Smith, Elizabeth Stempkowski, Daniel Arminavage, Robert Wilson, Rhonda Lincoln, David A Kaminsky, Erika Gonyaw, Chloe Housenger, Kevin Hodgdon, Heidi Pecott-Grimm, Jeffrey L Curtis, Lisa McCloskey, Nadia Hansel, Vera Bittner, James Tonascia, Sandy Snyder, Usamah Kayyali
Abstract
Background: Observational studies suggest that beta-blockers may reduce the risk of exacerbations and death in patients with moderate or severe chronic obstructive pulmonary disease (COPD), but these findings have not been confirmed in randomized trials.
Methods: In this prospective, randomized trial, we assigned patients between the ages of 40 and 85 years who had COPD to receive either a beta-blocker (extended-release metoprolol) or placebo. All the patients had a clinical history of COPD, along with moderate airflow limitation and an increased risk of exacerbations, as evidenced by a history of exacerbations during the previous year or the prescribed use of supplemental oxygen. We excluded patients who were already taking a beta-blocker or who had an established indication for the use of such drugs. The primary end point was the time until the first exacerbation of COPD during the treatment period, which ranged from 336 to 350 days, depending on the adjusted dose of metoprolol.
Results: A total of 532 patients underwent randomization. The mean (±SD) age of the patients was 65.0±7.8 years; the mean forced expiratory volume in 1 second (FEV1) was 41.1±16.3% of the predicted value. The trial was stopped early because of futility with respect to the primary end point and safety concerns. There was no significant between-group difference in the median time until the first exacerbation, which was 202 days in the metoprolol group and 222 days in the placebo group (hazard ratio for metoprolol vs. placebo, 1.05; 95% confidence interval [CI], 0.84 to 1.32; P = 0.66). Metoprolol was associated with a higher risk of exacerbation leading to hospitalization (hazard ratio, 1.91; 95% CI, 1.29 to 2.83). The frequency of side effects that were possibly related to metoprolol was similar in the two groups, as was the overall rate of nonrespiratory serious adverse events. During the treatment period, there were 11 deaths in the metoprolol group and 5 in the placebo group.
Conclusions: Among patients with moderate or severe COPD who did not have an established indication for beta-blocker use, the time until the first COPD exacerbation was similar in the metoprolol group and the placebo group. Hospitalization for exacerbation was more common among the patients treated with metoprolol. (Funded by the Department of Defense; BLOCK COPD ClinicalTrials.gov number, NCT02587351.).
Copyright © 2019 Massachusetts Medical Society.
Figures
Source: PubMed