Blood thinners, commonly referred to as oral anticoagulants, are usually prescribed to prevent blood clots that can lead to a stroke or other problems caused by lack of blood flow to an organ. Direct oral anticoagulants (DOACs) are the newest class of such oral anticoagulants and have a similar effect compared to the traditionally used drugs, such as warfarin. A big advantage of DOACs is that they do not require regular blood monitoring for which patients need to visit an anticoagulation clinic.
However, there is still some uncertainty concerning the safety of DOACs, especially with respect to the risk of bleeding. Particularly, not a lot of data is available to answer the question whether co-administration of other prescription drugs that strengthen the effect of the DOACs do result in an increased bleeding risk in DOAC users. Therefore, in this study, we aim to assess the risk of bleeding in patients using DOACs who at the same time use other drugs that might alter the effect of these anticoagulants.
The effect and clinical relevance of drug-drug interaction of DOACs in relation to bleeding is largely unknown.
Objective
To assess the risk of bleeding associated with concomitant use of drugs having pharmacokinetic or pharmacodynamic interactions on the anticoagulant effect of DOACs.
Methods
A case control study nested within a cohort of incident users of DOACs. Cases are patients with a first hospital admission for a major bleeding event. For each patient, up to 4 controls will be matched by region, sex, year of birth (+/- 1 year) and index date (the date of major bleeding event). Both cases and controls require to be a current user of DOACs on the index date. Concurrent use will be defined as prescribing of drug that have pharmacokinetic or pharmacodynamic interactions on the anticoagulant effect of DOACs.
Data analysis
Differences in baseline characteristics between cases and controls will be assessed by T-tests for continuous variables and Chi-square tests for categorical variables. Conditional logistic regression analysis will be used to estimate the strength of the association between concomitant use of potential interacting medication on the risk of major bleeding, expressed and crude and adjusted odds ratios (ORs) with 95% confidence intervals (CIs).
Anthonius de Boer - Chief Investigator - Utrecht University
Patrick Souverein - Corresponding Applicant - Utrecht University
Anke-Hilse Maitland-van der Zee - Collaborator - University of Amsterdam
Helga Gardarsdottir - Collaborator - Utrecht University
Hendrika van den Ham - Collaborator - Utrecht University
Yumao Zhang - Collaborator - Utrecht Institute for Pharmaceutical Sciences
HES Admitted Patient Care;Practice Level Index of Multiple Deprivation