Direct oral anticoagulants (DOACs), a drug class of oral anticoagulant (OACs) to thin the blood in people with heart diseases are increasingly used compared with the older alternative, warfarin. As many people taking blood thinning treatment may also take many different medications, it may increase the risk of interactions between medications. Some studies suggested how drugs interact with OACs but need further investigation. Whether DOACs have lower risk of interactions with drugs than warfarin is also uncertain. Further, proton pump inhibitors (PPIs) is a group of medications used to treat digestive disorders. There is a need to understand whether the treatment effects of OACs would be compromised and the risk of bleeding in stomach and intestines would be lowered by concurrently taking PPIs and OACs.
This project will study the health consequence after concurrently taking OACs and other drugs in the UK. Using anonymised electronic health records, we will study whether there is higher risk of adverse outcomes when concurrently taking OACs and these medications. We will also compare the impact of concurrently taking DOAC and those drugs with that of concurrently taking warfarin and those drugs.
We will also compare the results using different study methods. These analyses can facilitate the method development to study drug-drug interactions.
We aim to quantify the health consequences of co-prescription of oral anticoagulants (OACs) and a range of commonly used drugs including cardiovascular drugs, cyclosporine, antibiotics, antifungal treatment, selective serotonin reuptake inhibitors, phenytoin and proton pump inhibitors.
We will identify new DOACs and warfarin users, aged 18 or above during 1/1/2011-31/03/2021 using the data from the Clinical Practice Research Datalink. We will use a cohort study with propensity score and case-crossover study design to investigate if 1) concomitant use of DOACs and other drugs are associated with a higher risk of clinical outcomes, compared with DOAC alone; 2) concomitant use of warfarin and other drugs are associated with a higher risk of clinical outcomes, compared with warfarin alone; 3) concomitant use of DOACs and other drugs have a lower risk of clinical outcomes compared with concomitant use of warfarin and other drugs. Outcomes will include cardiovascular events, bleeding and mortality.
Using cohort study, we will identify four exposure groups (DOAC plus concomitant drug, DOAC alone, warfarin plus concomitant drug and warfarin alone). We will compare the hazards of each outcome among the exposed group with each comparison group using inverse probability treatment weighting Cox proportional-hazard models.
Using case-crossover study, we will compare each individual’s exposure in a time period prior to the outcome to that during a control period within an individual using conditional logistic regression.
To investigate the impact of using different approaches for case-crossover study, we will repeat the analyses limiting to people with both OAC exposures and outcomes. In the main analysis, we will use 1/1/2011-09/12/2019 as the study period to avoid the impact of change in exposure/outcome recording due to lockdown during COVID pandemic. We will repeat all analyses including recent data (study period: 1/1/2011-31/03/2021) to evaluate the impact of misclassification bias of exposure/outcome on the findings.
Effectiveness outcomes: ischaemic stroke, myocardial infarction, venous thromboembolism and cardiovascular death and all-cause mortality.
Safety outcomes: intracranial and/or gastrointestinal bleeding, other-bleeding
Yun "Angel" Wong - Chief Investigator - London School of Hygiene & Tropical Medicine ( LSHTM )
Yun "Angel" Wong - Corresponding Applicant - London School of Hygiene & Tropical Medicine ( LSHTM )
Amitava Banerjee - Collaborator - University College London ( UCL )
Charlotte Warren-Gash - Collaborator - London School of Hygiene & Tropical Medicine ( LSHTM )
Clemence Leyrat - Collaborator - London School of Hygiene & Tropical Medicine ( LSHTM )
HAN HAN - Collaborator - London School of Hygiene & Tropical Medicine ( LSHTM )
Hei Yeung Chan - Collaborator - London School of Hygiene & Tropical Medicine ( LSHTM )
Ian Douglas - Collaborator - London School of Hygiene & Tropical Medicine ( LSHTM )
Karin Seifert - Collaborator - London School of Hygiene & Tropical Medicine ( LSHTM )
Krishnan Bhaskaran - Collaborator - London School of Hygiene & Tropical Medicine ( LSHTM )
Lamprini Lampro - Collaborator - London School of Hygiene & Tropical Medicine ( LSHTM )
Marco Chau - Collaborator - London School of Hygiene & Tropical Medicine ( LSHTM )
Zixuan Wang - Collaborator - London School of Hygiene & Tropical Medicine ( LSHTM )
CHAN HEI YEUNG - Collaborator - London School of Hygiene & Tropical Medicine ( LSHTM )
Lamprini Lampro - Collaborator - London School of Hygiene & Tropical Medicine ( LSHTM )
Marco Chau - Collaborator - Not from an Organisation
HES Admitted Patient Care;ONS Death Registration Data;Patient Level Index of Multiple Deprivation;Practice Level Index of Multiple Deprivation