Bisoprolol in Patients With COPD at High Risk of Exacerbation

Importance: Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide. Observational studies report that β-blocker use may be associated with reduced risk of COPD exacerbations. However, a recent trial reported that metoprolol did not reduce COPD exacerbations and increased COPD exacerbations requiring hospital admission.

Objective: To test whether bisoprolol decreased COPD exacerbations in people with COPD at high risk of exacerbations.

Design, Setting and Participants: The Bisoprolol in COPD Study (BICS) was a double-blind placebo-controlled randomized clinical trial conducted in 76 UK sites (45 primary care clinics and 31 secondary clinics). Patients with COPD who had at least moderate airflow obstruction on spirometry (FEV1/FVC <0.7, FEV1 <80% predicted) and ≥2 COPD exacerbations treated with oral corticosteroids and/or antibiotics in the prior 12 months were enrolled from October 17, 2018, to May 31, 2022. Follow-up concluded on April 18, 2023.

Interventions: Patients were randomly assigned to bisoprolol (n=261) or placebo (n=258). Bisoprolol was started at 1.25 mg orally daily and was titrated as tolerated over 4 sessions to a maximum dose of 5 mg/d using a standardized protocol.

Main outcomes and Measures: The primary clinical outcome was the number of patient reported COPD exacerbations treated with oral corticosteroids and/or antibiotics over the 1- year treatment period. Safety outcomes included serious adverse events and adverse reactions.

Results: Although the trial planned to enroll 1574 patients, recruitment was suspended from March, 16, 2020, to July 31, 2021, due to the COVID-19 pandemic. Two patients in each group were excluded post randomization. Among the 515 patients (mean age, 68 years; men, 274 [53%]; mean FEV1, 50.1%, primary outcome data were available for 514 (99.8%) and 371 (72%) remained on study drug. The primary outcome of patient-reported COPD exacerbations treated with oral corticosteroids and/or antibiotics was 526 in bisoprolol group, with a mean exacerbation rate of 2.03/year vs 513 exacerbations in the placebo group with a mean exacerbation rate of 2.01/year, adjusted incidence rate ratio (IRR) [95% CI, 0.97 (0.84, 1.13), p=0.72]. Serious adverse events occurred in 37 (14.5%) of the bisoprolol group vs 36 (14.3%) in the placebo group, [relative risk 1.01 95% CI, 0.62, 1.66), p=0.96].

Conclusions and Relevance: Among people with COPD at high risk of exacerbation, treatment with bisoprolol did not reduce the number of self-reported COPD exacerbations requiring treatment with oral corticosteroids and/or antibiotics.