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. D.Allen Cooper, Gerard J. Criner, Jeffrey L. Curtis, Mei Lan 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 LindbergBarry 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

Research output: Contribution to journalArticle

2 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)2304-2314
Number of pages11
JournalNew England Journal of Medicine
Volume381
Issue number24
DOIs
StatePublished - Dec 12 2019

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Metoprolol
Chronic Obstructive Pulmonary Disease
Placebos
Hospitalization
Confidence Intervals
Medical Futility
Forced Expiratory Volume
Random Allocation
Observational Studies
Disease Progression
Oxygen
Safety

PubMed: MeSH publication types

  • Journal Article
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, U.S. Gov't, Non-P.H.S.

Cite this

Dransfield, M. T., Voelker, H., Bhatt, S. P., Brenner, K., Casaburi, R., Come, C. E., ... Connett, J. E. (2019). Metoprolol for the prevention of acute exacerbations of COPD. New England Journal of Medicine, 381(24), 2304-2314. https://doi.org/10.1056/NEJMoa1908142

Metoprolol for the prevention of acute exacerbations of COPD. / Dransfield, Mark T.; Voelker, Helen; Bhatt, Surya P.; Brenner, Keith; Casaburi, Richard; Come, Carolyn E.; Cooper, J. D.Allen; Criner, Gerard J.; Curtis, Jeffrey L.; Han, Mei Lan K.; Hatipoğlu, Umur; Helgeson, Erika S.; Jain, Vipul V.; Kalhan, Ravi; Kaminsky, David; Kaner, Robert; Kunisaki, Ken M.; Lambert, Allison A.; Lammi, Matthew R.; Lindberg, Sarah; Make, Barry J.; Martinez, Fernando J.; McEvoy, Charlene; Panos, Ralph J.; Reed, Robert M.; Scanlon, Paul D.; Sciurba, Frank C.; Smith, Anthony; Sriram, Peruvemba S.; Stringer, William W.; Weingarten, Jeremy A.; Wells, J. Michael; Westfall, Elizabeth; Lazarus, Stephen C.; Connett, John E.

In: New England Journal of Medicine, Vol. 381, No. 24, 12.12.2019, p. 2304-2314.

Research output: Contribution to journalArticle

Dransfield, MT, Voelker, H, Bhatt, SP, Brenner, K, Casaburi, R, Come, CE, Cooper, JDA, Criner, GJ, Curtis, JL, Han, MLK, Hatipoğlu, U, Helgeson, ES, Jain, VV, Kalhan, R, Kaminsky, D, Kaner, R, Kunisaki, KM, Lambert, AA, Lammi, MR, Lindberg, S, Make, BJ, Martinez, FJ, McEvoy, C, Panos, RJ, Reed, RM, Scanlon, PD, Sciurba, FC, Smith, A, Sriram, PS, Stringer, WW, Weingarten, JA, Wells, JM, Westfall, E, Lazarus, SC & Connett, JE 2019, 'Metoprolol for the prevention of acute exacerbations of COPD', New England Journal of Medicine, vol. 381, no. 24, pp. 2304-2314. https://doi.org/10.1056/NEJMoa1908142
Dransfield MT, Voelker H, Bhatt SP, Brenner K, Casaburi R, Come CE et al. Metoprolol for the prevention of acute exacerbations of COPD. New England Journal of Medicine. 2019 Dec 12;381(24):2304-2314. https://doi.org/10.1056/NEJMoa1908142
Dransfield, Mark T. ; Voelker, Helen ; Bhatt, Surya P. ; Brenner, Keith ; Casaburi, Richard ; Come, Carolyn E. ; Cooper, J. D.Allen ; Criner, Gerard J. ; Curtis, Jeffrey L. ; Han, Mei Lan K. ; Hatipoğlu, Umur ; Helgeson, Erika S. ; Jain, Vipul V. ; Kalhan, Ravi ; Kaminsky, David ; Kaner, Robert ; Kunisaki, Ken M. ; Lambert, Allison A. ; Lammi, Matthew R. ; Lindberg, Sarah ; Make, Barry J. ; Martinez, Fernando J. ; McEvoy, Charlene ; Panos, Ralph J. ; Reed, Robert M. ; Scanlon, Paul D. ; Sciurba, Frank C. ; Smith, Anthony ; Sriram, Peruvemba S. ; Stringer, William W. ; Weingarten, Jeremy A. ; Wells, J. Michael ; Westfall, Elizabeth ; Lazarus, Stephen C. ; Connett, John E. / Metoprolol for the prevention of acute exacerbations of COPD. In: New England Journal of Medicine. 2019 ; Vol. 381, No. 24. pp. 2304-2314.
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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.",
author = "Dransfield, {Mark T.} and Helen Voelker and Bhatt, {Surya P.} and Keith Brenner and Richard Casaburi and Come, {Carolyn E.} and Cooper, {J. D.Allen} and Criner, {Gerard J.} and Curtis, {Jeffrey L.} and Han, {Mei Lan K.} and Umur Hatipoğlu and Helgeson, {Erika S.} and Jain, {Vipul V.} and Ravi Kalhan and David Kaminsky and Robert Kaner and Kunisaki, {Ken M.} and Lambert, {Allison A.} and Lammi, {Matthew R.} and Sarah Lindberg and Make, {Barry J.} and Martinez, {Fernando J.} and Charlene McEvoy and Panos, {Ralph J.} and Reed, {Robert M.} and Scanlon, {Paul D.} and Sciurba, {Frank C.} and Anthony Smith and Sriram, {Peruvemba S.} and Stringer, {William W.} and Weingarten, {Jeremy A.} and Wells, {J. Michael} and Elizabeth Westfall and Lazarus, {Stephen C.} and Connett, {John E.}",
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TY - JOUR

T1 - Metoprolol for the prevention of acute exacerbations of COPD

AU - Dransfield, Mark T.

AU - Voelker, Helen

AU - Bhatt, Surya P.

AU - Brenner, Keith

AU - Casaburi, Richard

AU - Come, Carolyn E.

AU - Cooper, J. D.Allen

AU - Criner, Gerard J.

AU - Curtis, Jeffrey L.

AU - Han, Mei Lan K.

AU - Hatipoğlu, Umur

AU - Helgeson, Erika S.

AU - Jain, Vipul V.

AU - Kalhan, Ravi

AU - Kaminsky, David

AU - Kaner, Robert

AU - Kunisaki, Ken M.

AU - Lambert, Allison A.

AU - Lammi, Matthew R.

AU - Lindberg, Sarah

AU - Make, Barry J.

AU - Martinez, Fernando J.

AU - McEvoy, Charlene

AU - Panos, Ralph J.

AU - Reed, Robert M.

AU - Scanlon, Paul D.

AU - Sciurba, Frank C.

AU - Smith, Anthony

AU - Sriram, Peruvemba S.

AU - Stringer, William W.

AU - Weingarten, Jeremy A.

AU - Wells, J. Michael

AU - Westfall, Elizabeth

AU - Lazarus, Stephen C.

AU - Connett, John E.

PY - 2019/12/12

Y1 - 2019/12/12

N2 - 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.

AB - 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.

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