@article{01HEK3FKPHZJZNS8AWD79FGWGJ,
  abstract     = {{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.}},
  author       = {{Grymonprez, Maxim and Capiau, Andreas and Steurbaut, Stephane and Boussery, Koen and Mehuys, Els and Somers, Annemie and Petrovic, Mirko and De Backer, Tine and Lahousse, Lies}},
  issn         = {{0920-3206}},
  journal      = {{CARDIOVASCULAR DRUGS AND THERAPY}},
  keywords     = {{Atrial fibrillation,NOAC,pharmacodynamic drug-drug interaction,bleeding,antiplatelet,SSRI}},
  language     = {{eng}},
  number       = {{1}},
  pages        = {{133--143}},
  title        = {{Pharmacodynamic drug-drug interactions and bleeding outcomes in patients with atrial fibrillation using non-vitamin K antagonist oral anticoagulants : a nationwide cohort study}},
  url          = {{http://doi.org/10.1007/s10557-023-07521-5}},
  volume       = {{39}},
  year         = {{2025}},
}

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