Chronic obstructive pulmonary disease, or COPD for short is a disease that people get either due to smoking or air pollution and is also known as chronic bronchitis or emphysema. People with chronic obstructive pulmonary disease (COPD) are treated with inhalers to alleviate symptoms and ease breathing. Inhaled corticosteroids are one type of inhaler and have been shown to improve lung function and reduce chest infections (also called exacerbations), which are episodes where symptoms become worse (often trigged by a respiratory infection). On the other hand, inhaled corticosteroids have been found to increase the chance of pneumonia. It has since been recommended that people who don’t have lots of infections can stop their inhaled corticosteroids (if they are also on other inhalers). However, inhaled corticosteroids have been shown to have a potential protective effect on developing heart disease, so research is needed to better understand whether stopping inhaled corticosteroids will increase the chance of someone developing heart disease. Studies that have already investigated the relationship between inhaled corticosteroids and heart disease have mostly been randomised control trials which include very specific populations of people with COPD and have a very short follow-up period. In this study, we will use routine data to investigate the association between using inhaled corticosteroids and developing heart disease and what happens to heart disease risk when inhaled corticosteroids are stopped.
Chronic Obstructive Pulmonary Disease (COPD) patients are treated with short/long-acting bronchodilator inhalers. If symptoms persist or patients experience exacerbations of COPD, they are prescribed inhaled corticosteroids (ICS). The risks and benefits of ICS in the treatment of COPD are debated as whilst ICS has been shown to improve lung function (forced expiratory volume in 1 second (FEV1)) and reduce the risk of exacerbations, they have also been associated with increased risk of pneumonia. The WISDOM trial found that patients withdrawing from ICS but remaining on long-acting bronchodilators, had a similar risk of exacerbations to those who remained on triple therapy. It is now recommended that patients should be withdrawn from ICS if they are not frequent exacerbators and if they have low blood eosinophils. Despite this, evidence suggests that ICS may be protective of developing cardiovascular disease (CVD). CVD is important to investigate as it is the most common comorbidity in people with COPD due to shared risk factors and increased inflammation associated with COPD. Most studies that have investigated the association between ICS and CVD have been randomised control trials with short follow-up periods and specific populations of COPD patients. With this in mind, we aim to investigate the association between ICS use (both prevalent and incident use) and time to CVD event in a CVD naive populations of COPD patients over a 10 year follow up and investigate the association between ICS withdrawal and time to CVD. This will use CPRD Aurum data linked with HES and ONS to investigate GP recorded events, hospitalisations, and deaths from CVD causes. We plan to use Cox regression to investigate the association between ICS and time to first CVD event in a COPD population who do not have a history of CVD.
The primary outcome of interest is time to first cardiovascular disease event. This will include any of the following events: myocardial infarction, heart failure, ischemic stroke, arrythmia, and coronary heart disease (excluding MI). This outcome has been used before when investigating lung function decline and time to first CVD [1]. Composite CVD will be the first cardiovascular event during follow-up. Specifically, cardiovascular disease events will include GP recorded events (using CPRD Aurum data), hospitalised events (using HES), and mortality events (ONS).
Secondary outcomes will investigate each component of the composite CVD outcome separately if the data allow. We will not report any results where there are less than 5 events in a cell.
Jennifer Quint - Chief Investigator - Imperial College London
Hannah Whittaker - Corresponding Applicant - Imperial College London
Anne Ioannides - Collaborator - Imperial College London
Constantinos Kallis - Collaborator - Imperial College London
HES Admitted Patient Care;ONS Death Registration Data;Patient Level Index of Multiple Deprivation