Abstract
PurposeTo study the association between interacting drugs and bleeding or thromboembolism in atrial fibrillation outpatients treated with non-vitamin K antagonist oral anticoagulants (NOACs).MethodsPopulation-based cohort study of outpatients treated with NOACs in Sweden from 2008 to 2017. Patients with atrial fibrillation and newly initiated NOAC treatment were identified in the Prescribed Drug Register. Comorbidities and outcome data were retrieved from the Patient Register and the Cause of Death Register. Cox-regression analyses were performed to evaluate the primary endpoints any severe bleed and ischemic stroke/transient ischemic attack/stroke unspecified during the first six months of treatment. Secondary endpoints were gastrointestinal bleeding, intracranial bleeding, ischemic stroke, and venous thromboembolism.ResultsIncreased risk of any severe bleed was found when NOAC treatment, and drugs with pharmacodynamic effect on bleeding were combined, compared to NOAC only. An increased risk with these combinations was evident for apixaban (hazard ratio (HR) 1.47; 95% CI 1.33–1.63), rivaroxaban (HR 1.7; 95% CI 1.49–1.92), and dabigatran (HR 1.26; 95% CI 1.05–1.52). For apixaban, there was an increased risk of any severe bleed when combined with CYP3A4 and/or P-glycoprotein (P-gp) inhibitors (HR 1.23; 95% CI 1.01–1.5). The use of inducers of CYP3A4 and/or P-gp was low in this cohort, and effects on ischemic stroke/TIA/stroke unspecified could not be established.ConclusionIncreased risk of bleeding was seen for pharmacodynamic and pharmacokinetic interactions with NOACs. Prescribers need to be vigilant of the effect of interacting drugs on the risk profile of patients treated with NOACs.
Highlights
Non-vitamin K antagonist oral anticoagulants (NOACs) have become increasingly utilized in Sweden and the rest of the world during the past two decades, and the drug group is the first-line treatment for stroke prevention in atrial fibrillation [1,2,3,4]
The aim of this study was to evaluate whether concomitant treatment with NOACs and interacting drugs was associated with increased risks of bleeding or thromboembolic events in patients with atrial fibrillation in Swedish outpatient care, compared to the use of NOAC only
The percentages of patients with apixaban, rivaroxaban, and dabigatran were 61, 24, and 15% (Table 1)
Summary
Non-vitamin K antagonist oral anticoagulants (NOACs) have become increasingly utilized in Sweden and the rest of the world during the past two decades, and the drug group is the first-line treatment for stroke prevention in atrial fibrillation [1,2,3,4]. Patients risk formation of intracardiac thrombi as a consequence of atrial fibrillation, leading to systemic embolism and ischemic stroke, or hemorrhages due to treatment with anticoagulants. The risk-benefit profile of NOACs has proved superior to warfarin or no treatment [1, 5, 6]. Multimorbidity and polypharmacy add to the risks requiring attention in the treatment of patients with atrial fibrillation.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
