TY - JOUR
T1 - Pharmacodynamic Drug-Drug Interactions and Bleeding Outcomes in Patients with Atrial Fibrillation Using Non-Vitamin K Antagonist Oral Anticoagulants
T2 - a Nationwide Cohort Study
AU - Grymonprez, Maxim
AU - Capiau, Andreas
AU - Steurbaut, Stephane
AU - Boussery, Koen
AU - Mehuys, Els
AU - Somers, Annemie
AU - Petrovic, Mirko
AU - De Backer, Tine L.
AU - Lahousse, Lies
N1 - Publisher Copyright:
© The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2023.
PY - 2025/2
Y1 - 2025/2
N2 - Purpose: Pharmacodynamic drug-drug interactions (PD DDIs) may influence the safety of non-vitamin K antagonist oral anticoagulants (NOACs), but the extent to which PD DDIs increase bleeding risks, remains unclear. Therefore, the impact of PD DDIs on bleeding outcomes in NOAC-treated patients with atrial fibrillation (AF) was investigated. Methods: Using Belgian nationwide data, NOAC-treated AF patients were included between 2013–2019. Concomitant use of PD interacting drugs when initiating NOAC treatment was identified.Results: Among 193,072 patients, PD DDIs were identified in 114,122 (59.1%) subjects. After multivariable adjustment, concomitant use of PD interacting drugs was associated with significantly higher risks of major or clinically-relevant non-major bleeding (adjusted hazard ratio (aHR) 1.19, 95% confidence interval (CI) (1.13–1.24)), gastrointestinal (aHR 1.12, 95%CI (1.03–1.22)), urogenital (aHR 1.21, 95%CI (1.09–1.35)) and other bleeding (aHR 1.28, 95%CI (1.20–1.36)), compared to NOAC-treated AF patients without PD interacting drug use. Increased bleeding risks were most pronounced with P2Y12 inhibitors (aHR 1.62, 95%CI (1.48–1.77)) and corticosteroids (aHR 1.53, 95%CI (1.42–1.66)), followed by selective serotonin or serotonin and norepinephrine reuptake inhibitors (SSRI/SNRI, aHR 1.26, 95%CI (1.17–1.35)), low-dose aspirin (aHR 1.14, 95%CI (1.08–1.20)) and non-steroidal anti-inflammatory drugs (NSAID, aHR 1.10, 95%CI (1.01–1.21)). Significantly higher intracranial bleeding risks in NOAC users were observed with SSRI/SNRIs (aHR 1.50, 95%CI (1.25–1.81)) and corticosteroids (aHR 1.49, 95%CI (1.21–1.84)). Conclusion: Concomitant use of PD interacting drugs, especially P2Y12 inhibitors and corticosteroids, was associated with higher major, gastrointestinal, urogenital, and other bleeding risks in NOAC-treated AF patients. Remarkably, higher intracranial bleeding risks were observed with SSRI/SNRIs and corticosteroids.
AB - Purpose: Pharmacodynamic drug-drug interactions (PD DDIs) may influence the safety of non-vitamin K antagonist oral anticoagulants (NOACs), but the extent to which PD DDIs increase bleeding risks, remains unclear. Therefore, the impact of PD DDIs on bleeding outcomes in NOAC-treated patients with atrial fibrillation (AF) was investigated. Methods: Using Belgian nationwide data, NOAC-treated AF patients were included between 2013–2019. Concomitant use of PD interacting drugs when initiating NOAC treatment was identified.Results: Among 193,072 patients, PD DDIs were identified in 114,122 (59.1%) subjects. After multivariable adjustment, concomitant use of PD interacting drugs was associated with significantly higher risks of major or clinically-relevant non-major bleeding (adjusted hazard ratio (aHR) 1.19, 95% confidence interval (CI) (1.13–1.24)), gastrointestinal (aHR 1.12, 95%CI (1.03–1.22)), urogenital (aHR 1.21, 95%CI (1.09–1.35)) and other bleeding (aHR 1.28, 95%CI (1.20–1.36)), compared to NOAC-treated AF patients without PD interacting drug use. Increased bleeding risks were most pronounced with P2Y12 inhibitors (aHR 1.62, 95%CI (1.48–1.77)) and corticosteroids (aHR 1.53, 95%CI (1.42–1.66)), followed by selective serotonin or serotonin and norepinephrine reuptake inhibitors (SSRI/SNRI, aHR 1.26, 95%CI (1.17–1.35)), low-dose aspirin (aHR 1.14, 95%CI (1.08–1.20)) and non-steroidal anti-inflammatory drugs (NSAID, aHR 1.10, 95%CI (1.01–1.21)). Significantly higher intracranial bleeding risks in NOAC users were observed with SSRI/SNRIs (aHR 1.50, 95%CI (1.25–1.81)) and corticosteroids (aHR 1.49, 95%CI (1.21–1.84)). Conclusion: Concomitant use of PD interacting drugs, especially P2Y12 inhibitors and corticosteroids, was associated with higher major, gastrointestinal, urogenital, and other bleeding risks in NOAC-treated AF patients. Remarkably, higher intracranial bleeding risks were observed with SSRI/SNRIs and corticosteroids.
UR - https://www.scopus.com/pages/publications/85175797844
U2 - 10.1007/s10557-023-07521-5
DO - 10.1007/s10557-023-07521-5
M3 - Article
C2 - 37930588
AN - SCOPUS:85175797844
SN - 0920-3206
VL - 39
SP - 133
EP - 143
JO - Cardiovascular Drugs and Therapy
JF - Cardiovascular Drugs and Therapy
IS - 1
ER -