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

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

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.

Study Overview

• Status: Completed
• Conditions: Pulmonary Disease, Chronic Obstructive

Detailed Description

Purpose:

• Study Type: Observational
• Enrollment (Actual): 115397

Contacts and Locations

Study Locations

• Canada
  • Quebec
    • Montreal, Quebec, Canada
      • Boehringer Ingelheim Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 55 years to 100 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Users of tiotropium or long-acting beta agonists

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

5

Cohorts and Interventions

Group / Cohort
LABA + tiotropium
LABA mono
neither tiotropium nor LABA
tiotropium + LABA
tiotropium mono

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: March 1, 2014
• Primary Completion (Actual): August 1, 2015
• Study Completion (Actual): August 1, 2015

Study Registration Dates

• First Submitted: March 24, 2014
• First Submitted That Met QC Criteria: March 24, 2014
• First Posted (Estimate): March 26, 2014

Study Record Updates

• Last Update Posted (Actual): February 15, 2017
• Last Update Submitted That Met QC Criteria: December 22, 2016
• Last Verified: December 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive
• Other Study ID Numbers: 205.526