Abstract
This study aimed to compare and determine the prevalence of drug–drug interaction (DDI) and bleeding rate in atrial fibrillation (AF) patients receiving anticoagulants in a clinical setting. We used large claims data of AF patients obtained from the Japan Medical Data Center. The prevalence of DDIs and cases leading to bleeding events were surveyed clinically relevant DDIs extracted from 1) reported from a spontaneous adverse event reporting system (Japanese Adverse Drug Events Report system; JADER) ≥4 patients; 2) DDIs cited in the package inserts of each anticoagulant (each combination assessed according to “Drug interaction 2015” list; 3) warfarin and quinolone antibiotics DDIs. DDIs were categorized the mechanisms for pharmacokinetic DDI (Cytochrome P450 (CYP) or transporter etc. that modulate blood concentration of anticoagulants)/pharmacodynamic DDI (combination with similar pharmacological actions) or both in the analysis for each patients’ prescriptions obtained from a claims data. AF patients were compared between cases with and without bleeding after administered of anticoagulants. Bleeding was observed in 220/3290 (6.7%) AF patients. The bleeding rate in patients with both pharmacokinetic and pharmacodynamic DDI mechanisms (26.3%) was higher than that in patients with either mechanism (8.6% and 9.2%, respectively) or without DDIs (4.9%). The odds ratio for bleeding in AF patients with both of pharmacokinetic and pharmacodynamic was (7.18 [4.69–11.00], p<0.001). Our study concluded multi mechanism based DDIs leads serious outcome as compared to that of single mechanism based DDIs in AF patients. We determined the prevalence and frequency of bleeding for anticoagulant-related DDIs. To manage DDIs, both pharmacokinetic and pharmacodynamic DDI mechanisms should be closely monitored for initial symptoms of bleeding within the first 3 months.
Highlights
In the present decade, the number of patients with atrial fibrillation (AF) has gradually increased in parallel with the extended lifespan [1]
The prevalence of drug–drug interactions (DDIs) and cases leading to bleeding events were surveyed clinically relevant DDIs extracted from 1) reported from a spontaneous adverse event reporting system (Japanese Adverse Drug Events Report system; JADER) 4 patients; 2) DDIs cited in the package inserts of each anticoagulant warfarin and quinolone antibiotics DDIs
A retrospective survey reported that 26% of adverse events for direct hospital admissions were caused by drug–drug interactions (DDIs) [2]
Summary
The number of patients with atrial fibrillation (AF) has gradually increased in parallel with the extended lifespan [1]. The treatment of AF includes rhythm control and prevention of thrombosis using anticoagulants, such as warfarin or direct oral anticoagulants (apixaban, edoxaban, dabigatran, and rivaroxaban). These anticoagulants are known to exhibit pharmacodynamic DDIs with antiplatelet drugs and pharmacokinetic DDIs with cytochrome P450 (CYP) or transporter inhibitors, inducing bleeding events. The co-administration of anticoagulants, azole antifungals, and amiodarone increased the risk of major bleeding [6]. Data on these situations, including those on any bleeding in real-world clinical settings, are insufficient because of the limited case reports and pharmaceutical information. The number of cases with DDIs reported is generally insufficient in hospital or community pharmacies
Sign-in/Register to view highlights & summary 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 callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
