β-Blockers are associated with a reduction in COPD exacerbations

Abstract

Background: While some retrospective studies have suggested that β-blocker use in patients with COPD is associated with a reduction in the frequency of acute exacerbations and lower mortality, there is concern that their use in patients with severe COPD on home oxygen may be harmful.

Methods: Subjects with Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage 2-4 COPD participating in a prospective follow-up of the COPDGene cohort, a multicentre observational cohort of current and former smokers were recruited. Total and severe exacerbation rates were compared between groups categorised by β-blocker use on longitudinal follow-up using negative binomial regression analyses, after adjustment for demographics, airflow obstruction, %emphysema on CT, respiratory medications, presence of coronary artery disease, congestive heart failure and coronary artery calcification, and after adjustment for propensity to prescribe β-blockers.

Results: 3464 subjects were included. During a median of 2.1 years of follow-up, β-blocker use was associated with a significantly lower rate of total (incidence risk ratio (IRR) 0.73, 95% CI 0.60 to 0.90; p=0.003) and severe exacerbations (IRR 0.67, 95% CI 0.48 to 0.93; p=0.016). In those with GOLD stage 3 and 4 and on home oxygen, use of β-blockers was again associated with a reduction in the rate of total (IRR 0.33, 95% CI 0.19 to 0.58; p<0.001) and severe exacerbations (IRR 0.35, 95% CI 0.16 to 0.76; p=0.008). Exacerbation reduction was greatest in GOLD stage B. There was no difference in all-cause mortality with β-blocker use.

Conclusions: β-Blockers are associated with a significant reduction in COPD exacerbations regardless of severity of airflow obstruction. The findings of this study should be tested in a randomised, placebo-controlled trial.

Trial registration number: (ClinicalTrials.gov NCT00608764).

Keywords: COPD Exacerbations.

Conflict of interest statement

SPB has grant support from the American Heart Association. He has no conflicts of interest relevant to this manuscript. JMW’s institution has contracts with GSK and Forest. Dr. Wells has no conflicts of interest relevant to this manuscript. JEH receives grant support from the National Health Lung and Blood Institute and from the American Diabetes Association. Dr. Hokanson has no conflicts of interest relevant to this manuscript. In the past three years, EKS received honoraria and consulting fees from Merck and grant support and consulting fees from GSK. GRW reports receiving consulting fees from Merck and GSK. His spouse works for Merck. WCB has received personal fees from DLA Piper. MTD has served as a consultant for GSK, BI, Boston Scientific and Ikaria. His institution has received research grant support from AHA, NHLBI, GSK and Forest and has received contracted support for enrolment in clinical trials from Aeris, AstraZeneca, BI, Boston Scientific, Centocor, GSK, Forest, Otsuka, Pearl, Pfizer, PneumRx, and Pulmonx. GLK, YK, JC and HN have no conflicts of interest to declare.

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Figures

Figure 1

shows comparison of adjusted Incidence Risk Ratios (IRR) for total and severe exacerbations occurring during long term follow-up in patients with chronic obstructive pulmonary disease (COPD) who are on or not on β-blocker therapy. These rates were adjusted for total exacerbations by age, gender, race, smoking burden, body mass index, forced expiratory volume in the first second (FEV1), %emphysema on computed tomography, coronary artery calcification, presence of congestive heart failure and coronary artery disease, long acting respiratory medications, and for the propensity to prescribe β-blockers based on demographics, coronary artery disease, congestive heart failure and severity of airflow obstruction. Rates were adjusted for severe exacerbations by age, race, forced expiratory volume in the first second (FEV1), %emphysema on computed tomography, coronary artery calcification, presence of congestive heart failure, long acting respiratory medications, and for the propensity to prescribe β-blockers. All values expressed as Odds Ratios (95% Confidence Intervals). SQRQ = St. George’s Respiratory Questionnaire. MMRC = Modified Medical Research Council Dyspnea Scale. Prescription adj = adjusted for propensity to prescribe β-blockers based on demographics, coronary artery disease, congestive heart failure and severity of airflow obstruction. SGRQ and MMRC adj = adjusted for propensity to prescribe β-blockers based on demographics, coronary artery disease, congestive heart failure and severity of airflow obstruction, as well as respiratory quality of life using SGRQ and dyspnea per MMRC score. **p