Concurrent use of P-glycoprotein or Cytochrome 3A4 drugs and non-vitamin K antagonist oral anticoagulants in non-valvular atrial fibrillation

Abstract Aim To determine the concurrent use of P-glycoprotein (P-gp) or Cytochrome (CYP) 3A4 drugs and non-vitamin K antagonist oral anticoagulants (NOACs) among non-valvular AF (NVAF) patients in clinical practice. Methods and results Administrative databases identified all adults (≥18 years) with...

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Published in:	European heart journal. Quality of care & clinical outcomes 2022-03, Vol.8 (2), p.195-201
Main Authors:	Sandhu, Roopinder K, Islam, Sunjidatul, Dover, Douglas C, Andrade, Jason G, Ezekowitz, Justin, McAlister, Finlay A, Hawkins, Nathaniel M, Kaul, Padma
Format:	Article
Language:	eng
Subjects:	Administration, Oral Alberta Antagonist drugs Anticoagulants ATP Binding Cassette Transporter, Subfamily B, Member 1 - therapeutic use Atrial Fibrillation - complications Atrial Fibrillation - drug therapy Cardiac arrhythmia Cytochrome Cytochromes - therapeutic use Drug interactions Glycoproteins Humans
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Summary:	Abstract Aim To determine the concurrent use of P-glycoprotein (P-gp) or Cytochrome (CYP) 3A4 drugs and non-vitamin K antagonist oral anticoagulants (NOACs) among non-valvular AF (NVAF) patients in clinical practice. Methods and results Administrative databases identified all adults (≥18 years) with incident or prevalent NVAF who initiated a NOAC in an outpatient or inpatient setting, between July 2012 and March 2019 in Alberta, Canada. Concurrent use was defined as a P-gp or CYP3A4 dispensation in the 100 days prior to and overlapping NOAC dispensation. The P-gp and CYP3A4 drugs were categorized into three groups and drug-drug interactions classified according to the 2018 European Heart Rhythm Association practical guide. Time-varying Cox models calculated the crude hazard ratio (HR) of outcomes at 1-year. A total of 642 255 NOAC dispensations occurred for 36 566 NVAF patients. Of these, 71 643 (11.2%) had a concurrent dispensation of an interacting P-gp or CYP3A4 drug. Overall, the drug–drug interaction was defined as contraindicated in 2.5%, avoid/caution in 2.3%, and for another 6.7% should require a dose adjustment. When all drug–drug interactions were considered, inappropriate NOAC prescribing occurred in 63% (n = 45 080) of dispensations. There was a significantly higher risk of death (HR 1.58, 1.47–1.70) for a drug–drug interaction but not for stroke (P = 0.89) or major bleeding risk (P = 0.13). Conclusions The concurrent use of P-gp or CYP3A4 drugs and NOACs was uncommon but important since almost two-thirds of patients with drug–drug interactions had inappropriate NOAC dosing and a higher risk of death. More attention to this issue is needed.
ISSN:	2058-5225 2058-1742