Combined Bronchodilators in Chronic Obstructive Pulmonary Disease and the Risk of Adverse Cardio-pulmonary Events

Study Overview
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Brief Summary
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Background: Recent observational studies have reported possible arrhythmogenic effects with long-acting beta-agonists (LABA), while the long-acting anticholinergic tiotropium has been associated with cardiovascular and cerebrovascular events. Finally, pneumonia was the object of a recent signal in trials of LABAs submitted for marketing approval. Aim: To assess the potential cardio-pulmonary risk arising from the concurrent use of two long-acting bronchodilators as well as from monotherapy use of each of the long-acting bronchodilators. Methods: A series of population-based cohort studies, using both cohort and nested case-control analyses will be conducted using data from the United Kingdom's Clinical Practice Research Datalink (CPRD). The base cohort will consist of new users of long-acting bronchodilators from Jan 2002 until Aug 2012, age >= 55 with chronic obstructive pulmonary disease (COPD) and at least two years of baseline medical history information. The high-dimensional propensity score technique will be used to match new users of each long-acting bronchodilator and new users of two bronchodilators with comparable subjects from the base cohort, with one-year follow-up for outcomes of acute myocardial infarction, stroke, heart failure, arrhythmia and community acquired pneumonia. Data will be analysed using time-dependent Cox proportional hazard regression models and conditional logistic regression models.

Detailed Description
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Purpose:

Official Title
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Combined Bronchodilators in Chronic Obstructive Pulmonary Disease and the Risk of Adverse Cardio-pulmonary Events: A Population-based Observational Study

Conditions
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Pulmonary Disease, Chronic Obstructive

Participation Criteria
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Eligibility Criteria
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Inclusion criteria: New users of long-acting bronchodilators, either a LABA or tiotropium, between January 2002 and August 2012 Age >= 55 years Exclusion criteria: - Use of LABA or tiotropium in the two years prior to cohort entry

Ages Eligible for Study
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Minimum Age: 55 Years
Maximum Age: 100 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| LABA + tiotropium<br> | |
| LABA mono<br> | |
| neither tiotropium nor LABA<br> | |
| tiotropium + LABA<br> | |
| tiotropium mono<br> | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Myocardial Infarction | The acute myocardial infarction (MI) rate per 1000 patients per year after matching on high-dimensional propensity score and inhaled corticosteroid (ICS) use in the year prior to cohort entry. No. = Number | Up to 12 months | 
| Stroke | The stroke rate per 1000 patients per year after matching on high-dimensional propensity score and inhaled corticosteroid (ICS) use in the year prior to cohort entry. | Up to 12 months | 
| Heart Failure | The heart failure (HF) rate per 1000 patients per year after matching on high-dimensional propensity score and inhaled corticosteroid (ICS) use in the year prior to cohort entry. | Up to 12 months | 
| Cardiac Arrhythmia | The cardiac arrhythmia (CA) rate per 1000 patients per year after matching on high-dimensional propensity score and inhaled corticosteroid (ICS) use in the year prior to cohort entry. | Up to 12 months | 
| Community Acquired Pneumonia | The community acquired pneumonia rate per 1000 patients per year after matching on high-dimensional propensity score and inhaled corticosteroid (ICS) use in the year prior to cohort entry. Pt. = Patient | Up to 12 months |