Dose adjustment or discontinuous use of direct oral anticoagulants related to the concurrent use of potential interacting drugs

Date of ISAC Approval: 
Lay Summary: 
Blood thinners 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 blood thinners and have a similar effect compared to the traditionally used drugs, such as warfarin. Co-administration of other prescription drugs that strengthen the effect of the DOACs may result in an increased bleeding risk in DOAC users. To avoid this complication, it is important to change the dose of the DOAC or stop its use. Our knowledge regarding the prescribing of DOACs under this condition is limited. Therefore, in this study, we aim to look how and what extend general practitioners adjust DOACs when the other drugs that strengthen the effect were prescribed.
Technical Summary: 
Background: Prescription patterns of direct oral anticoagulants (DOACs) are largely unknow before and during the concurrent use of interacting drugs. Compliance with labelling information is essential for the effective and safety use of DOACs. Objective This population-based descriptive study will assess prescribing patterns, including dosing adjustment, and discontinuation among DOACs users with concurrent use of interacting drugs. Methods A descriptive study will be conducted by using a cohort of DOAC users from the Clinical Practice Research Datalink (CPRD) data. The study period extends from 2008 to 2015. All patients 18+ years of age with first prescription of dabigatran, apixaban, and rivaroxaban are eligible. The number and proportion of dosing adjustment, or discontinuous use of DOACs during the initiation of concurrent use of potentially interacting drugs will be determined. Data analysis Descriptive statistics will be applied including frequencies and percentages. Number and percentage of DOACs users with dosing adjustment, or discontinuous use will be calculated.
Health Outcomes to be Measured: 
Dose adjustment, Discontinuation and switching

Anthonius de Boer - Chief Investigator - Utrecht University
Dr Anke-Hilse Maitland-van der Zee - Collaborator - University of Amsterdam
Mr Patrick C Souverein - Corresponding Applicant - Utrecht University
Yumao Zhang - Collaborator - Utrecht Institute for Pharmaceutical Sciences