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N Engl J Med. 2019 Oct 20. doi: 10.1056/NEJMoa1908142. [Epub ahead of print]

Metoprolol for the Prevention of Acute Exacerbations of COPD.

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From the Lung Health Center, University of Alabama at Birmingham (M.T.D., S.P.B., J.M.W., E.W.), and Birmingham Veterans Affairs (VA) Medical Center (M.T.D., J.A.D.C., J.M.W.) - both in Birmingham; the University of Minnesota (H.V., E.S.H., S.L., J.E.C.) and the Minneapolis VA Medical Center (K.M.K.), Minneapolis, HealthPartners Minnesota, Bloomington (C.M.), and Mayo Clinic, Rochester (P.D.S.) - all in Minnesota; New York-Presbyterian (NYP)-Columbia University Medical Center (K.B.), NYP-Weill Cornell Medical Center (R. Kaner, F.J.M.), NYP-Queens Medical Center (A.S.), and NYP-Brooklyn Methodist Medical Center (J.A.W.) - all in New York; Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Los Angeles (R.C., W.W.S.), the University of California, San Francisco-Fresno, Fresno (V.V.J.), and the University of California, San Francisco, San Francisco (S.C.L.) - all in California; Brigham and Women's Hospital, Boston (C.E.C.); Temple University School of Medicine, Philadelphia (G.J.C.); the Ann Arbor VA Medical Center (J.L.C.) and the University of Michigan Health System (M.K.H.) - both in Ann Arbor; the Cleveland Clinic, Cleveland (U.H.); Northwestern University, Chicago (R. Kalhan); the University of Vermont, Burlington (D.K.); the University of Washington, Seattle (A.A.L.); Louisiana State University, New Orleans (M.R.L.); National Jewish Health, Denver (B.J.M.); the Cincinnati VA Medical Center, Cincinnati (R.J.P.); the University of Maryland, Baltimore (R.M.R.); the University of Pittsburgh, Pittsburgh (F.C.S.); and North Florida-South Georgia Veterans Health System, Gainesville (P.S.S.).



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.


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.


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.


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 number, NCT02587351.).


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