Chronic Obstructive Pulmonary Disease (COPD) is a lung disease where people experience symptoms such as cough, sputum and breathlessness. People with the condition are advised to stop smoking and are also sometimes given inhalers that help to open the airways and decrease inflammation. These inhalers can help to reduce symptoms and disease flare ups, known as exacerbations.
We know that people with COPD often have cardiovascular diseases such as heart attacks, and heart failure. What we do not know is that if by using some inhalers, we can decrease the risk of a person with COPD having a heart attack or heart failure for example. Using routinely collected electronic healthcare records we wish to understand whether some inhalers used to treat COPD reduce heart attacks and heart failure for example directly, or if the reason the heart attacks and heart failure are reduced is because the inhalers reduce the inflammation and disease flare ups that people with COPD get. This is really important to understand as it may change the way in which we prescribe inhalers for people with COPD.
Chronic Obstructive Pulmonary Disease (COPD) is a progressive respiratory disease, characterised by airway obstruction. People with COPD exist as a spectrum of traits and phenotypes, and they are not all alike in their disease characteristics or disease severity. COPD is treated (in addition to lifestyle interventions) using inhalers, namely bronchodilators (long-acting beta agonists [LABA] and long-acting muscarinic antagonists [LAMA]), and inhaled corticosteroids (ICS).
There is a well-established association between COPD and cardiovascular disease, include major adverse cardiovascular events (MACE). There is mixed evidence, however, to suggest that ICS may reduce MACE risk due to a reduction in the inflammatory mechanistic pathways that co-exist between COPD and cardiovascular disease. Whilst some post hoc analyses have found a cardioprotective effect of ICS, most observational research (and most meta-analyses and systematic reviews of all study types) have concluded that there is largely no association between ICS and MACE. It is possible that the mixed evidence is due to the heterogeneity in the COPD population, indicating that any relationship between ICS and MACE is indirect, and potentially mediated by respiratory factors.
Therefore, using Clinical Practice Research Datalink (CPRD) Aurum primary care data, linked with Hospital Episode Statistics (HES) secondary care data and Office of National Statistics (ONS) death data, we will conduct a cohort study between 1 January 2012 and up to the latest HES linkage availability, on people with a COPD diagnosis, prescribed some sort of LABA, LAMA, or ICS. We will compare MACE outcomes (including acute coronary syndrome, arrhythmia, ischaemic stroke, heart failure, or cardiovascular-specific death) between people prescribed ICS with people prescribed a long-acting bronchodilator in the absence of ICS directly, as well as indirectly through stratification and mediation analysis. We will consider mediators directly pertaining to COPD disease severity and phenotype, infection profile, and inflammatory burden.
Major adverse cardiovascular events (MACE) as a composite, as well as the individual subtypes thereof. MACE subtypes include:
- Acute coronary syndrome (ACS, including myocardial infarction),
- Ischaemic stroke (henceforth stroke),
- Arrhythmia,
- Heart failure (HF) hospitalisation, and
- Cardiovascular-specific death (CV-death).
Jennifer Quint - Chief Investigator - Imperial College London
Anne Ioannides - Corresponding Applicant - Imperial College London
Alex Bottle - Collaborator - Imperial College London
HES Admitted Patient Care;ONS Death Registration Data;Patient Level Index of Multiple Deprivation