Pulmonary Disease, Chronic Obstructive
Conditions
Brief summary
Examine the risk of cardiovascular events (cardiac arrhythmia or myocardial ischemia) or all-cause mortality in Chronic Obstructive Pulmonary Disease (COPD) patients who are new users of Olodaterol or other LABAs available for the treatment of COPD.
Detailed description
Purpose: Time Perspective:
Interventions
None listed
Sponsors
Boehringer Ingelheim
Study design
Observational model
COHORT
Time perspective
OTHER
Eligibility
Sex/Gender
ALL
Age
40 Years to 100 Years
Healthy volunteers
No
Inclusion criteria
* COPD diagnosis * aged 40 years or older (to minimise the likelihood of including individuals who have asthma only) * New user of olodaterol or a new user of indacaterol, salmeterol, or formoterol (not in fixed-dose combination with an inhaled corticosteroid) and have no dispensing of any LABA in the 6 months before the index date * at least 1 year of enrolment in the electronic database before their first LABA dispensing (defined as the index LABA) * Complete data on sex
Exclusion criteria
none
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Occurrence of First Hospitalisation or Hospital Outpatient Clinic Visit for Atrial Fibrillation or Flutter (AF) | Up to 4 years and 11 months | Cases of AF were ascertained by at least one (=first occurrence) International Statistical Classification of Diseases and Related Health Problems, 10th Revision (ICD-10) code for primary hospital inpatient discharge diagnosis or as a diagnosis code in a hospital outpatient specialist visit in the Danish National Patient Registry while being new users of olodaterol or of any Long-Acting Beta2-Agonist (LABA) other than olodaterol. The exposure window considered only the first episode of continuous use, defined as the time comprising consecutive dispensing's separated by up to 14 days. Termination dates of the follow up: date of outcome of interest, disenrollment from the database, 14 days after estimated discontinuation of the last dispensing for index LABA, the date the patient switched to another LABA, dispensing of a second LABA, death, end of study period (= 31 January 2019). |
| Occurrence of First Hospitalisation or Hospital Outpatient Clinic Visit for Supraventricular Tachycardia (SVT) (Other Than Atrial Fibrillation/Flutter) | Up to 4 years and 11 months | Cases of SVT were ascertained by at least one (=first occurrence) ICD-10 code for primary hospital inpatient discharge diagnosis or as a diagnosis code in a hospital outpatient specialist visit in the Danish National Patient Registry while being new users of olodaterol or of any Long-Acting Beta2-Agonist (LABA) other than olodaterol. The exposure window considered only the first episode of continuous use, defined as the time comprising consecutive dispensing's separated by up to 14 days. Termination dates of the follow up: date of outcome of interest, disenrollment from the database, 14 days after estimated discontinuation of the last dispensing for index LABA, the date the patient switched to another LABA, dispensing of a second LABA, death, end of study period (= 31 January 2019). |
| Occurrence of First Hospitalisation for Ventricular Tachycardia (VT), Including Ventricular Fibrillation/Flutter and Cardiac Arrest | Up to 4 years and 11 months | Cases of VT were ascertained by at least one (=first occurrence) ICD-10 code for primary hospital inpatient discharge diagnosis in the Danish National Patient Registry while being exposed to olodaterol and other LABA monotherapy or in free or fixed-dose combination with long-acting muscarinic antagonist (LAMA). The exposure window considered only the first episode of continuous use, defined as the time comprising consecutive dispensing's separated by up to 14 days. Termination dates of the follow up: date of outcome of interest, disenrollment from the database, 14 days after estimated discontinuation of the last dispensing for index LABA, the date the patient switched to another LABA, dispensing of a second LABA, death, end of study period (= 31 January 2019). |
| Occurrence of First Hospitalisation for Acute Myocardial Infarction (AMI) | Up to 4 years and 11 months | Cases of AMI were ascertained by at least one (=first occurrence) ICD-10 code for primary hospital inpatient discharge diagnosis in the Danish National Patient Registry while being new users of olodaterol or of any Long-Acting Beta2-Agonist (LABA) other than olodaterol. The exposure window considered only the first episode of continuous use, defined as the time comprising consecutive dispensing's separated by up to 14 days. Termination dates of the follow up: date of outcome of interest, disenrollment from the database, 14 days after estimated discontinuation of the last dispensing for index LABA, the date the patient switched to another LABA, dispensing of a second LABA, death, end of study period (= 31 January 2019). |
| Occurrence of First Hospitalisation for Serious Acute Coronary Heart Disease (SACHD), Including Angina and Other Acute Ischaemic Heart Disease Events | Up to 4 years and 11 months. | Cases of SACHD were ascertained by at least one (=first occurrence) ICD-10 code for primary hospital inpatient discharge diagnosis in the Danish National Patient Registry while being new users of olodaterol or of any Long-Acting Beta2-Agonist (LABA) other than olodaterol. The exposure window considered only the first episode of continuous use, defined as the time comprising consecutive dispensing's separated by up to 14 days. Termination dates of the follow up: date of outcome of interest, disenrollment from the database, 14 days after estimated discontinuation of the last dispensing for index LABA, the date the patient switched to another LABA, dispensing of a second LABA, death, end of study period (= 31 January 2019). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| All-cause Mortality. | Up to 4 years and 11 months. | Death ascertained from Danish Civil Registration System (fact and date of death, but not cause of death) while being new users of olodaterol or any Long-Acting Beta2-Agonist (LABA) other than olodaterol. Exposure window: first episode of continuous use (= time comprising consecutive dispensing's separated by up to 14 days). Termination dates of the follow up: date of outcome of interest, disenrollment from database, 14 days after estimated discontinuation of last dispensing for index LABA, date patient switched to another LABA, dispensing of a second LABA, death, end of study period (= 31 January 2019). To assess possible impact of imbalanced baseline characteristics, all-cause mortality was further assessed in two post-hoc analyses with restricted populations that would be more similar at baseline, post-hoc population 1 and post-hoc population 2. |
Countries
Denmark
Participant flow
Recruitment details
This cohort study, used data from the Danish National Patient Registry (diagnoses), Danish Prescription Database (dispensings), and Danish Register of Causes of Death (cause of death information) to examine the risk of cardiovascular events in patients with chronic obstructive pulmonary disease (COPD) exposed to olodaterol compared to other long-acting beta2-agonists (LABAs) between 01 March 2014 and 31 January 2019.
Pre-assignment details
Only subjects that met all inclusion and none of the exclusion criteria were included. The matched cohort study design and propensity score methodology were used to establish two comparable treatment cohorts, the Olodaterol cohort and the other LABA cohort.
Participants by arm
| Arm | Count |
|---|---|
| Olodaterol Cohort of patients with Obstructive Pulmonary Disease (COPD) derived from the Danish Patient Registry initiating olodaterol (either alone or in free- or fixed-dose combination with a Long-Acting Muscarinic Antagonist (LAMA)), with first dispensing as index date occurred from 01 March 2014 (launch of olodaterol in Denmark) to 31 January 2019 (last date with data available for the final data cut).
Participants were matched 1:4 ('olodaterol' : 'other LABAs') by age, sex, and calendar year. | 14,239 |
| Other Long-acting beta2-agonist (LABAs) Cohort of patients with Obstructive Pulmonary Disease (COPD) derived from the Danish Patient Registry (March 2014 to January 2019) initiating LABA (alone or in a free- or fixed-dose combination with a LAMA), with first dispensing as index date occurred from 01 March 2014 (launch of olodaterol in Denmark) to 31 January 2019 (last date with data available for the final data cut).
Participants were matched 1:4 ('olodaterol' : 'other LABAs') by age, sex, and calendar year. | 51,167 |
| Total | 65,406 |
Baseline characteristics
| Characteristic | Olodaterol | Other Long-acting beta2-agonist (LABAs) | Total |
|---|---|---|---|
| Age, Continuous | 72.7 Years STANDARD_DEVIATION 10 | 72.7 Years STANDARD_DEVIATION 10 | 72.7 Years STANDARD_DEVIATION 10 |
| Race and Ethnicity Not Collected | — | — | 0 Participants |
| Sex: Female, Male Female | 7649 Participants | 27253 Participants | 34902 Participants |
| Sex: Female, Male Male | 6590 Participants | 23914 Participants | 30504 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 859 / 14,239 | 1,872 / 51,167 |
| other Total, other adverse events | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 0 / 0 | 0 / 0 |
Outcome results
Primary
Occurrence of First Hospitalisation for Acute Myocardial Infarction (AMI)
Cases of AMI were ascertained by at least one (=first occurrence) ICD-10 code for primary hospital inpatient discharge diagnosis in the Danish National Patient Registry while being new users of olodaterol or of any Long-Acting Beta2-Agonist (LABA) other than olodaterol. The exposure window considered only the first episode of continuous use, defined as the time comprising consecutive dispensing's separated by up to 14 days. Termination dates of the follow up: date of outcome of interest, disenrollment from the database, 14 days after estimated discontinuation of the last dispensing for index LABA, the date the patient switched to another LABA, dispensing of a second LABA, death, end of study period (= 31 January 2019).
Time frame: Up to 4 years and 11 months
Population: Propensity score-trimmed population of patients with Chronic Obstructive Pulmonary Disease (COPD) derived from the Danish Patient Registry.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Olodaterol | Occurrence of First Hospitalisation for Acute Myocardial Infarction (AMI) | 56 Events |
| Other Long-acting beta2-agonist (LABAs) | Occurrence of First Hospitalisation for Acute Myocardial Infarction (AMI) | 137 Events |
Comparison: No formal hypotheses were tested.95% CI: [0.79, 1.87]Poisson regression model
Primary
Occurrence of First Hospitalisation for Serious Acute Coronary Heart Disease (SACHD), Including Angina and Other Acute Ischaemic Heart Disease Events
Cases of SACHD were ascertained by at least one (=first occurrence) ICD-10 code for primary hospital inpatient discharge diagnosis in the Danish National Patient Registry while being new users of olodaterol or of any Long-Acting Beta2-Agonist (LABA) other than olodaterol. The exposure window considered only the first episode of continuous use, defined as the time comprising consecutive dispensing's separated by up to 14 days. Termination dates of the follow up: date of outcome of interest, disenrollment from the database, 14 days after estimated discontinuation of the last dispensing for index LABA, the date the patient switched to another LABA, dispensing of a second LABA, death, end of study period (= 31 January 2019).
Time frame: Up to 4 years and 11 months.
Population: Propensity score-trimmed population of patients with Chronic Obstructive Pulmonary Disease (COPD) derived from the Danish Patient Registry.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Olodaterol | Occurrence of First Hospitalisation for Serious Acute Coronary Heart Disease (SACHD), Including Angina and Other Acute Ischaemic Heart Disease Events | 41 Events |
| Other Long-acting beta2-agonist (LABAs) | Occurrence of First Hospitalisation for Serious Acute Coronary Heart Disease (SACHD), Including Angina and Other Acute Ischaemic Heart Disease Events | 147 Events |
Comparison: No formal hypotheses were tested.95% CI: [0.64, 1.56]Poisson regression model
Primary
Occurrence of First Hospitalisation for Ventricular Tachycardia (VT), Including Ventricular Fibrillation/Flutter and Cardiac Arrest
Cases of VT were ascertained by at least one (=first occurrence) ICD-10 code for primary hospital inpatient discharge diagnosis in the Danish National Patient Registry while being exposed to olodaterol and other LABA monotherapy or in free or fixed-dose combination with long-acting muscarinic antagonist (LAMA). The exposure window considered only the first episode of continuous use, defined as the time comprising consecutive dispensing's separated by up to 14 days. Termination dates of the follow up: date of outcome of interest, disenrollment from the database, 14 days after estimated discontinuation of the last dispensing for index LABA, the date the patient switched to another LABA, dispensing of a second LABA, death, end of study period (= 31 January 2019).
Time frame: Up to 4 years and 11 months
Population: Propensity score-trimmed population of patients with Chronic Obstructive Pulmonary Disease (COPD) derived from the Danish Patient Registry.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Olodaterol | Occurrence of First Hospitalisation for Ventricular Tachycardia (VT), Including Ventricular Fibrillation/Flutter and Cardiac Arrest | 29 Events |
| Other Long-acting beta2-agonist (LABAs) | Occurrence of First Hospitalisation for Ventricular Tachycardia (VT), Including Ventricular Fibrillation/Flutter and Cardiac Arrest | 80 Events |
Comparison: No formal hypotheses were tested.95% CI: [0.71, 2.36]Poisson regression model
Primary
Occurrence of First Hospitalisation or Hospital Outpatient Clinic Visit for Atrial Fibrillation or Flutter (AF)
Cases of AF were ascertained by at least one (=first occurrence) International Statistical Classification of Diseases and Related Health Problems, 10th Revision (ICD-10) code for primary hospital inpatient discharge diagnosis or as a diagnosis code in a hospital outpatient specialist visit in the Danish National Patient Registry while being new users of olodaterol or of any Long-Acting Beta2-Agonist (LABA) other than olodaterol. The exposure window considered only the first episode of continuous use, defined as the time comprising consecutive dispensing's separated by up to 14 days. Termination dates of the follow up: date of outcome of interest, disenrollment from the database, 14 days after estimated discontinuation of the last dispensing for index LABA, the date the patient switched to another LABA, dispensing of a second LABA, death, end of study period (= 31 January 2019).
Time frame: Up to 4 years and 11 months
Population: Propensity score-trimmed population of patients with Chronic Obstructive Pulmonary Disease (COPD) derived from the Danish Patient Registry
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Olodaterol | Occurrence of First Hospitalisation or Hospital Outpatient Clinic Visit for Atrial Fibrillation or Flutter (AF) | 246 Events |
| Other Long-acting beta2-agonist (LABAs) | Occurrence of First Hospitalisation or Hospital Outpatient Clinic Visit for Atrial Fibrillation or Flutter (AF) | 725 Events |
95% CI: [0.98, 1.47]Poisson regression model
Primary
Occurrence of First Hospitalisation or Hospital Outpatient Clinic Visit for Supraventricular Tachycardia (SVT) (Other Than Atrial Fibrillation/Flutter)
Cases of SVT were ascertained by at least one (=first occurrence) ICD-10 code for primary hospital inpatient discharge diagnosis or as a diagnosis code in a hospital outpatient specialist visit in the Danish National Patient Registry while being new users of olodaterol or of any Long-Acting Beta2-Agonist (LABA) other than olodaterol. The exposure window considered only the first episode of continuous use, defined as the time comprising consecutive dispensing's separated by up to 14 days. Termination dates of the follow up: date of outcome of interest, disenrollment from the database, 14 days after estimated discontinuation of the last dispensing for index LABA, the date the patient switched to another LABA, dispensing of a second LABA, death, end of study period (= 31 January 2019).
Time frame: Up to 4 years and 11 months
Population: Propensity score-trimmed population of patients with Chronic Obstructive Pulmonary Disease (COPD) derived from the Danish Patient Registry.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Olodaterol | Occurrence of First Hospitalisation or Hospital Outpatient Clinic Visit for Supraventricular Tachycardia (SVT) (Other Than Atrial Fibrillation/Flutter) | 19 Events |
| Other Long-acting beta2-agonist (LABAs) | Occurrence of First Hospitalisation or Hospital Outpatient Clinic Visit for Supraventricular Tachycardia (SVT) (Other Than Atrial Fibrillation/Flutter) | 38 Events |
Comparison: No formal hypotheses were tested.95% CI: [0.9, 3.74]Poisson regression model
Secondary
All-cause Mortality.
Death ascertained from Danish Civil Registration System (fact and date of death, but not cause of death) while being new users of olodaterol or any Long-Acting Beta2-Agonist (LABA) other than olodaterol. Exposure window: first episode of continuous use (= time comprising consecutive dispensing's separated by up to 14 days). Termination dates of the follow up: date of outcome of interest, disenrollment from database, 14 days after estimated discontinuation of last dispensing for index LABA, date patient switched to another LABA, dispensing of a second LABA, death, end of study period (= 31 January 2019). To assess possible impact of imbalanced baseline characteristics, all-cause mortality was further assessed in two post-hoc analyses with restricted populations that would be more similar at baseline, post-hoc population 1 and post-hoc population 2.
Time frame: Up to 4 years and 11 months.
Population: Propensity score-trimmed population of patients with Chronic Obstructive Pulmonary Disease (COPD) derived from the Danish Patient Registry. Post-hoc population 1 was based on propensity score-trimmed population restricted to users of fixed-dose combination of LABA/LAMA who were LABA-treatment naïve (= no LABA dispensing in the 180 days before cohort entry). Post-hoc population 2 was post-hoc population 1 further restricted to users without hospitalizations for COPD in the last 90 days.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Olodaterol | All-cause Mortality. | 859 Events |
| Other Long-acting beta2-agonist (LABAs) | All-cause Mortality. | 1872 Events |
Comparison: Analysis was based on Propensity score-trimmed population of patients with Chronic Obstructive Pulmonary Disease (COPD) derived from the Danish Patient Registry.95% CI: [1.44, 1.84]Poisson regression model
Comparison: Analysis based on post-hoc population 1.~Adjustments: propensity score decile, previous use of: LAMA, oxygen, inhaled glucocorticoid, respiratory medications, fixed-dose combinations of Short-Acting Beta2- Agonist and Short-Acting Muscarinic Antagonist and systemic antibacterials. COPD severity, number of: all-cause hospitalisations 365 and 180 days, COPD exacerbations 180 and 90 days, COPD hospitalisations 180 and 90 days, and COPD exacerbations 90 days before index date.95% CI: [1.23, 1.78]Poisson regression model
Comparison: Analysis based on post-hoc population 2. Adjustments: propensity score decile, previous use of: LAMA, oxygen, inhaled glucocorticoid, respiratory medications. COPD severity, number of all-cause hospitalisations 180 days, COPD exacerbations 180 days before cohort entry.95% CI: [0.97, 1.64]Poisson regression model