Pulmonary Disease, Chronic Obstructive
Conditions
Brief summary
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
Purpose:
Interventions
None listed
Sponsors
Boehringer Ingelheim
Study design
Observational model
COHORT
Time perspective
RETROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
55 Years to 100 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Myocardial Infarction | Up to 12 months | 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 |
| Stroke | Up to 12 months | 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. |
| Heart Failure | Up to 12 months | 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. |
| Cardiac Arrhythmia | Up to 12 months | 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. |
| Community Acquired Pneumonia | Up to 12 months | 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 |
Countries
Canada
Participant flow
Recruitment details
The base cohort included 115,397 new users of tiotropium or a LABA (+/- ICS) between 01Jan2002 & 31Aug2013.These patients included 26,442 new users of tiotropium & 88,955 new users of LABA.Patients initiating treatment with both bronchodilators on the same date were excluded.
Pre-assignment details
Patients receiving combination therapy were those who either added tiotropium to LABA, or added LABA to tiotropium. In the Participant Flow & Baseline Characteristics modules, no participants were represented in both the Tiotropium & the LABA Arms/Groups.
Participants by arm
| Arm | Count |
|---|---|
| Tiotropium Participants who were new users of tiotropium. | 26,442 |
| LABA Participants who were new users of a long-acting beta2 agonist (LABA) with or without inhaled corticosteroid (ICS). | 88,955 |
| Total | 115,397 |
Baseline characteristics
| Characteristic | Tiotropium | LABA | Total |
|---|---|---|---|
| Age, Continuous | 71.5 Years STANDARD_DEVIATION 9 | 69.4 Years STANDARD_DEVIATION 9.4 | 69.9 Years STANDARD_DEVIATION 9.3 |
| Gender Female | 11741 Participants | 48912 Participants | 60653 Participants |
| Gender Male | 14701 Participants | 40043 Participants | 54744 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 0 / 0 | 0 / 0 |
Outcome results
Primary
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.
Time frame: Up to 12 months
Population: The subset of patients from the base cohort who were either on monotherapy (who stayed on monotherapy) or combination therapy (who added tiotropium to LABA or added LABA to tiotropium), who can be linked to the Hospital Episode Statistics database, and were matched via propensity score.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Monotherapy | Cardiac Arrhythmia | 10.0 No. of incident CA/1000patients /year |
| Combination Therapy | Cardiac Arrhythmia | 10.7 No. of incident CA/1000patients /year |
95% CI: [0.81, 1.36]
Primary
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
Time frame: Up to 12 months
Population: The subset of patients from the base cohort who were either on monotherapy (who stayed on monotherapy) or combination therapy (who added tiotropium to LABA or added LABA to tiotropium), who can be linked to the Hospital Episode Statistics database, and were matched via propensity score.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Monotherapy | Community Acquired Pneumonia | 63.0 No.of incident Pneumonia/1000 pt./year |
| Combination Therapy | Community Acquired Pneumonia | 84.6 No.of incident Pneumonia/1000 pt./year |
95% CI: [1.23, 1.5]
Primary
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.
Time frame: Up to 12 months
Population: The subset of patients from the base cohort who were either on monotherapy (who stayed on monotherapy) or combination therapy (who added tiotropium to LABA or added LABA to tiotropium) and were matched via propensity score.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Monotherapy | Heart Failure | 29.3 No. of incident HF/1000patients/year |
| Combination Therapy | Heart Failure | 33.9 No. of incident HF/1000patients/year |
95% CI: [1.03, 1.3]
Primary
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
Time frame: Up to 12 months
Population: The subset of patients from the base cohort who were either on monotherapy (who stayed on monotherapy) or combination therapy (who added tiotropium to LABA or added LABA to tiotropium) and were matched via propensity score.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Monotherapy | Myocardial Infarction | 10.1 No. of incident MI/1000patients/ year |
| Combination Therapy | Myocardial Infarction | 11.3 No. of incident MI/1000patients/ year |
95% CI: [0.92, 1.37]
Primary
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.
Time frame: Up to 12 months
Population: The subset of patients from the base cohort who were either on monotherapy (who stayed on monotherapy) or combination therapy (who added tiotropium to LABA or added LABA to tiotropium) and were matched via propensity score.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Monotherapy | Stroke | 8.3 No. of incident stroke/1000patients/year |
| Combination Therapy | Stroke | 7.0 No. of incident stroke/1000patients/year |
95% CI: [0.69, 1.1]