Atrial fibrillation (AF) is a heart condition that promotes the formation of blood clumps which can block blood supply to the brain causing stroke, a serious and life-threatening condition. Oral anticoagulants, also known as blood thinners, are often offered to patients with AF to prevent stroke. Historically, oral anticoagulants called warfarin were commonly used, but newer and safer types of blood thinners called direct oral anticoagulants (DOACs), are now recommended over warfarin. Despite DOACs superior safety compared to warfarin, recent studies have linked DOACs to interstitial lung disease (ILD), a group of rare conditions which often cause serious complications in the lungs such as scarring. These complications can lead to breathing difficulties and death. Limited research has investigated this important safety concern; it is uncertain whether DOACs may increase the risk of ILD, or which patient groups may be most at risk of ILD with DOACs.
This study will use de-identified electronic databases to assess whether DOACs may increase the risk of ILD compared to warfarin in patients with AF. We will also compare the risk of ILD between DOACs. Furthermore, we will explore if certain patient groups may be more at risk of ILD with DOACs. These findings can inform whether guidelines should be aware for ILDs in patients with AF using DOACs. This would help prevent potentially DOAC-induced ILDs and allow timelier medical intervention.
Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia which increases the risk of embolic events such as ischaemic stroke. Direct oral anticoagulants (DOACs), which are at least as effective as warfarin with superior safety regarding adverse bleeding events, are recommended as the choice of oral anticoagulation for patients with AF. However, case reports, pharmacovigilance data and a recent observational study have linked DOACs, specifically FXa inhibitors, to an increased risk of interstitial lung disease (ILD). We will use the Clinical Practice Research Datalink, linked with Hospital Episode Statistics and Office of National Statistics, to investigate the association between DOACs and ILD.
This is a retrospective cohort study designed using the target trial framework. Patients with AF who initiated oral anticoagulants between 1 January 2012 and 31 December 2022 will be included in the study. We will compare the risk of ILD with DOAC vs warfarin as well as between DOACs. To control for confounding, we will use inverse probability treatment weights (IPTW). Propensity scores will be calculated using generalised boosted models, an iterative machine-learning algorithm. For each pairwise comparison, we will fit IPTW weighted Cox Proportional Hazards models to obtain adjusted hazard ratios. IPTW weighted pooled logistic regressions will be used to compute standardised risk curves for ILD at monthly intervals. Subgroup analyses will be performed to observe if certain patient groups may have increased ILD risk associated with DOACs. These findings can help inform whether guidelines should promote vigilance in monitoring for ILDs among patients with AF using DOACs, helping prevent DOAC-induced ILDs.
Interstitial Lung Disease
Wallis Lau - Chief Investigator - University College London ( UCL )
Jan Chobanov - Corresponding Applicant - University College London ( UCL )
Ian Wong - Collaborator - University College London ( UCL )
Kenneth Man - Collaborator - University College London ( UCL )
Olivia Bryant - Collaborator - University College London ( UCL )
HES Accident and Emergency;HES Admitted Patient Care;HES Diagnostic Imaging Dataset;HES Outpatient;ONS Death Registration Data;Patient Level Index of Multiple Deprivation;Practice Level Index of Multiple Deprivation;CPRD Aurum Ethnicity Record;CPRD GOLD Ethnicity Record