Metoprolol in Chronic Obstructive Pulmonary Disease without Cardiovascular Disease

BACKGROUND: Beta-blockers may improve outcomes in patients with chronic obstructive pulmonary disease (COPD) without cardiovascular disease, but randomized trials have been inconclusive. METHODS: This was a multicenter, open-label, pragmatic, phase 4 randomized trial. Patients 40 years of age or older with COPD, sinus rhythm, and no cardiovascular disease were randomly assigned in a 1:1 ratio to receive metoprolol, at a target dose of 100 mg daily, in addition to standard care or to receive standard care alone. The primary end point was the time to the first occurrence of a COPD exacerbation, cardiovascular event, or death during 1 year of follow-up. RESULTS: A total of 1695 patients underwent random assignment; their mean age was 70 years, and 62% were female. The primary end point occurred in 27% of patients assigned to receive metoprolol and in 30% assigned to receive standard care (hazard ratio, 0.87; 95% confidence interval [CI], 0.73 to 1.05; P=0.14). The corresponding hazard ratios were 0.88 (95% CI, 0.72 to 1.06) for COPD exacerbations, 0.73 (95% CI, 0.48 to 1.11) for cardiovascular events, 0.92 (95% CI, 0.48 to 1.77) for death, and 0.87 (95% CI, 0.58 to 1.28) for exacerbations requiring hospitalization. Serious adverse events occurred in 80 (9.4%) of 848 participants in the metoprolol group and 66 (7.8%) of 847 participants in the standard care group. Nonserious adverse events occurred in 293 (34.6%) of 848 patients in the metoprolol group and 247 (29.2%) of 847 in the standard care group. CONCLUSIONS: Among patients with COPD and no cardiovascular disease, metoprolol did not significantly improve the time to a composite of exacerbations, cardiovascular events, or death. (Funded by research grants from the Swedish Research Council and others; ClinicalTrials.gov number, NCT03566667.).