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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 2304-2314 |
| Number of pages | 11 |
| Journal | New England Journal of Medicine |
| Volume | 381 |
| Issue number | 24 |
| DOIs | |
| State | Published - Dec 12 2019 |
Bibliographical note
Funding Information:Supported by a grant (W81XWH-15-1-0705) from the Department of Defense.
Funding Information:
Dr. Dransfield reports receiving consulting fees and serving on clinical trials for Boehringer Ingelheim, GlaxoSmithKline, AstraZeneca, and PneumRx/BTG, serving on clinical trials for Novartis, Yungjin, Boston Scientific, Gala Therapeutics, and Nuvaira, receiving travel support and serving on clinical trials for Pulmonx, and receiving consulting fees from Quark Pharmaceuticals and Mereo; Dr. Bhatt, receiving advisory board fees from Sunovion and GlaxoSmithKline and research funding, paid to his institution, from ProterixBio; Dr. Casaburi, receiving grant support, advisory board fees, and lecture fees from Glaxo-SmithKline, Boehringer Ingelheim, and AstraZeneca, consulting fees from Regeneron and Genentech, and owning stock in Inogen; Dr. Come, receiving clinical trial support from Sunovion Pharmaceuticals; Dr. Criner, receiving grant support and consulting fees from Boehringer Ingelheim, grant support from Novartis, AstraZeneca, Respironics, MedImmune, Actelion, Forest, Pearl, Ikaria, Aeris, PneumRx, and Pulmonx, having an equity interest in Healthcare Solutions, receiving consulting fees from Amirall and Holaira, and receiving grant support and serving as a consultant for GlaxoSmithKline; Dr. Han, receiving consulting fees and honoraria from GlaxoSmithKline, AstraZeneca, and Boehringer Ingelheim, consulting fees from Mylan, and research support from Sunovion and Novartis; Dr. Jain, receiving consulting fees, advisory fees, and lecture fees from AstraZeneca Pharmaceuticals, Boehringer Ingelheim Pharmaceuticals, Genentech, Mallinckrodt, and GlaxoSmithKline; Dr. Kalhan, receiving grant support, consulting fees, and lecture fees from Boehringer Ingel-heim and GlaxoSmithKline, grant support from PneumRx/BTG and Spiration, grant support and consulting fees from Astra-Zeneca, and consulting fees from CVS Caremark, Aptus Health, Boston Scientific, and Boston Consulting Group; Dr. Kaminsky, receiving lecture fees from MGC Diagnostics; Dr. Kaner, receiving grant support, consulting fees, and lecture fees from Genen-tech and Boehringer Ingelheim, fees for serving on an adjudication committee from MedImmune and Gilead, and grant support from Bristol-Myers Squibb, Afferent, Respivant, and Toray; Dr. Kunisaki, receiving consulting fees from GlaxoSmith-Kline and Nuvaira; Dr. Make, receiving grant support, paid to National Jewish Health, fees for serving as an international principal investigator on a clinical trial, advisory board fees, and presentation fees from AstraZeneca, serving as a reviewer and serving on a data and safety monitoring board for Spiration, grant support, paid to National Jewish Health, advisory board fees, and presentation fees from GlaxoSmithKline, grant support, paid to National Jewish Health, and medical board fees from Sunovion, participating in CME activities for WebMD, Up-To-Date, Projects in Knowledge, Hybrid Communications, Med-scape, and Catamount Medical, serving as a consultant and on an advisory board for Novartis, receiving grant support, paid to National Jewish Health, from Pearl Therapeutics, advisory board fees from Verona, Boehringer Ingelheim, Theravance, Circassia, Phillips, and Science 24/7, consulting fees from Third Pole, and fees for serving on a data safety and monitoring board from Shire; Dr. Martinez, receiving advisory board fees, fees for serving on a steering committee, presentation fees, and travel support from AstraZeneca, advisory board fees, presentation fees, fees for serving on a data and safety monitoring board, and travel support from Boehringer Ingelheim, advisory board fees and trial support from ProterixBio, advisory board fees, fees for serving on a data and safety monitoring board, and travel sup-
Funding Information:
travel support from Canadian Respiratory Network, serving on a steering committee for Promedior, advisory board fees and travel support from Teva, and serving on an advisory board for Gala Therapeutics; Dr. McEvoy, receiving grant support from GlaxoSmithKline and consulting fees from Respirtech; Dr. Reed, receiving grant support from Janssen Research and Development; Dr. Scanlon, receiving grant support from AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, and Sanofi; Dr. Sciurba, receiving grant support from Astellas, AstraZeneca, PneumRx/ BTG, Pulmonx, Nuvaira, and Gala Therapeutics and advisory board fees from GlaxoSmithKline, Verona, and Theravance; Dr. Sriram, receiving grant support from AstraZeneca and Glaxo-SmithKline; Dr. Stringer, receiving grant support from Astra-Zeneca and Boehringer Ingelheim, consulting fees and fees for serving on a data and safety monitoring board from Allergan, and fees for serving on a data and safety monitoring board from Syneos Health; Dr. Wells, receiving grant support from Bayer, grant support and advisory board fees from GlaxoSmithKline and Mereo BioPharma, advisory board fees from Boehringer In-gelheim, and serving as end-point adjudicator for Quintiles and PRA Health Sciences; and Dr. Lazarus, receiving fees for education from Boehringer Ingelheim. No other potential conflict of interest relevant to this article was reported.
Publisher Copyright:
Copyright © 2019 Massachusetts Medical Society.
PubMed: MeSH publication types
- Journal Article
- Multicenter Study
- Randomized Controlled Trial
- Research Support, U.S. Gov't, Non-P.H.S.
