Chronic obstructive pulmonary disease (COPD) is a respiratory condition in which there is long-term decline in lung function. Symptoms are cough and breathlessness, with flare-ups during which symptoms become much worse. Many COPD patients already take statins for prevention of heart disease. Statins may have other beneficial uses as well as their main one to lower cholesterol. Some studies have found that statins might reduce the frequency and severity of COPD flare-ups, but a recent trial was stopped because there was no evidence of any benefit. These conflicting results may be because the trial only included patients with moderate-severe COPD and no pre-existing heart disease. Further, there may be problems with the design of some of the other studies. We will use data from the Clinical Practice Research datalink (CPRD) to investigate whether statins can reduce the severity and frequency of flare-ups. We will define statin use carefully so as not to bias our study. We will investigate the effects of statin use overall, by severity of COPD, and by pre-existing heart disease. If our results suggest that statin use reduces number or severity of COPD flare-ups, then they can be used to justify and plan new trials of statins for COPD.
Statins are widely used for prevention of cardiovascular disease (CVD), a significant comorbidity in COPD. There is increasing evidence that COPD is a systemic inflammatory disease and that statins have anti-inflammatory properties. Therefore, statins might reduce the severity/frequency of COPD exacerbations. Several observational studies have found statin use to be associated with lower exacerbation rates. However, a trial of simvastatin for preventing exacerbations was stopped early due to lack of benefit. It has been hypothesised that this was due to restriction of the trial population to people without CVD who would have lower levels of inflammation and therefore be least likely to benefit. Furthermore, the observational studies may have been subject to biases e.g. immortal-time or prevalent-user bias.
Given the high burden of exacerbations to the NHS and to individuals, and that statins are inexpensive and widely accepted, the possibility of statins having a direct role in COPD management should be investigated further. We will design a historical cohort study using the CPRD. Our population will include different severities of COPD. We will use a new-user design with propensity score matching to minimise bias. Our results would be used to justify (or not) and design another trial, including selection of subgroups most likely to benefit.
Primary outcome: Time to first exacerbation and exacerbation rate.
- Primary outcome: Severe exacerbation requiring hospitalisation
- Secondary outcome: all-cause mortality
- Secondary outcome: Urinary tract infection (negative control)
Margaret Smith - Chief Investigator - University of Oxford
Margaret Smith - Corresponding Applicant - University of Oxford
Christopher Butler - Collaborator - University of Oxford
Clare Bankhead - Collaborator - University of Oxford
Helen Ashdown - Collaborator - University of Oxford
James Sheppard - Collaborator - University of Oxford
HES Admitted Patient Care;ONS Death Registration Data;Patient Level Index of Multiple Deprivation