CHEST 2019 — Trial stopped early: higher risk of severe COPD exacerbations with metoprolol


  • Keren Landman, MD
  • Conference Reports
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Takeaway

  • Metoprolol increased the risk of severe exacerbations in patients with at least moderate COPD.

Why this matters

  • These findings contradict the results of observational studies suggesting beta-blockers may reduce risk of exacerbation and death in COPD patients.

Study design

  • Placebo-controlled, double-blinded, prospective, randomized, multicenter trial of 532 patients with COPD, at least moderate airflow limitation, and at increased risk for exacerbation based on past-year exacerbations or supplemental oxygen prescription.  
  • Patients taking or with indications to take a beta-blocker were excluded.
  • Patients randomly assigned to receive 50 mg metoprolol (later dose-adjusted) or placebo for 336 days.
  • The primary outcome assessed was time to first COPD exacerbation.
  • Funding: US Department of Defense.

Key results

  • Although there was no difference in time to first exacerbation, patients in the metoprolol group had increased risk of severe or very severe exacerbation (HR, 2.08 [95% CI, 1.37-3.14]).
  • The trial was terminated early due to safety concerns.

Limitations

  • Not possible to fully blind study due to expected physical effects of beta-blockade.
  • Results may not be generalizable to patients with less severe COPD or with indications to take a beta-blocker. 
  • Results may not be generalizable to all beta-blockers.
  • Power to identify high-risk groups limited due to early termination.

Expert commentary

  • Jean Bourbeau, senior scientist in the Translational Research in Respiratory Diseases Program at McGill University in Montreal, said the study's results should motivate clinicians to reconsider starting COPD patients on beta-blockers for preventive purposes. "It's a little bit more complicated to decide [whether to] stop patients that you have already started," he said, but suggested clinicians consider stopping the medication in patients who "have had any increase in their exacerbations, increase in their dyspnea, or any major complication in relation to their COPD," unless they have an indication for beta-blockade.