Chronic Obstructive Pulmonary Disease (COPD) is a lung disease characterized by increasing breathlessness that worsens over time. COPD is a major cause of disability and has become the third cause of death globally. Treatments attempt to prevent or delay acute exacerbations of COPD that contribute to worsen the disease over time and are associated with increased mortality. There is no cure and treatments revolve around symptom relief and controlling the inflammation from the disease. The current treatments, that include bronchodilators and inhaled corticosteroids, have been available for a long time with no new effective treatments. A large proportion of patients with COPD also have cardiovascular disease (CVD), such as myocardial infarction, stroke, or heart failure, etc. Both diseases share common risk factors such as smoking, increased age and decreased physical activity. Beta-blockers are old drugs that are effective for cardiovascular disease and have been suggested as potentially useful to improve outcomes in patients with COPD. A large trial found that this was not the case and suggested a possible increased mortality with beta-blockers in these patients. Our study will investigate whether beta-blockers used in patients with COPD increases the risk of death. This study will inform clinical recommendations on how to reduce harm and improve major outcomes for COPD patients worldwide.
The objective of this study is to evaluate the safety of beta-blocker use on the risk of death in patients with COPD. We will use the Clinical Practice Research Datalink (CPRD) to form a base cohort of patients with a COPD diagnosis, aged 55 or over, and treated with long-acting bronchodilators. We will use a prevalent new-user design to define the study cohort, whereby for each patient who initiates beta-blockers during follow-up, a time-conditional propensity score-matched reference subject, unexposed to beta-blockers, will be selected from the corresponding exposure set of patients with the same time since cohort entry, with the same indication for the beta-blocker, and with a visit to a physician at the time of the exposure set. Thus, the time span between base cohort entry and study cohort entry is inherently a matching covariate. Time-conditional propensity scores will be estimated using all relevant covariates, measured from diagnoses, procedures, and medications in the one-year period prior to the date of the matched set and applying conditional logistic regression. The matched subjects in the study cohort will be followed for one year from cohort entry, date of death, September 2023, or the end of coverage in the practice, whichever is first. The primary outcome is all-cause mortality while the secondary outcome is the first severe COPD exacerbation to occur after cohort entry, defined as a hospitalization for COPD as primary cause. For secondary outcome of severe COPD exacerbation, follow-up will end in March 2021, last date of availability (HES database). The comparative analysis of time to death and time to the first severe exacerbation within one year will use a Cox proportional hazard regression model to perform an as-treated analysis to estimate the hazard ratio of COPD exacerbation and mortality with current use of beta-blocker, also according to indication.
All-cause mortality; Severe COPD exacerbation
Samy Suissa - Chief Investigator - Sir Mortimer B Davis Jewish General Hospital
Samy Suissa - Corresponding Applicant - Sir Mortimer B Davis Jewish General Hospital
Pierre Ernst - Collaborator - McGill University
Sophie Dell'Aniello - Collaborator - McGill University
HES Admitted Patient Care