Arrhythmias & electrophysiology
Impact of P-glycoprotein and CYP3A4-interacting drugs on clinical outcomes in patients with atrial fibrillation using non-vitamin K antagonist oral anticoagulants: a nationwide cohort study
Authors' conclusion
Concomitant use of P-gp/CYP3A4 inhibitors was associated with higher bleeding and all-cause mortality risks in NOAC users, whereas the use of P-gp/CYP3A4 inducers was associated with higher stroke risks.
Study context
- Population
- NOAC-treated atrial fibrillation (AF) patients, Belgian nationwide data, 2013–2019
- Participants
- 193,072 patients
- Exposure
- P-glycoprotein (P-gp)/CYP3A4 inhibitor vs P-gp/CYP3A4 inducer
- P-gp/CYP3A4 inhibitorn = 46,194
- P-gp/CYP3A4 inducern = 2,903
- Outcome
- Major bleeding, thromboembolism (stroke) and all-cause mortality
Methodological detailsnationwide, multivariable-adjusted
- Nationwide
- Multivariable-adjusted
Main finding
As reported in the abstract
Adjusted hazard ratio (95% CI)
P-gp/CYP3A4 inhibitormajor bleeding
1.24(1.18–1.30)
P-gp/CYP3A4 inhibitorall-cause mortality
1.07(1.02–1.11)
P-gp/CYP3A4 inducerstroke
1.31(1.03–1.68)
Observational data: associations, not effects.
Further findings
Major bleeding, by interacting drug (inhibitors)
| Comparison | aHR (95% CI) | |
|---|---|---|
| Amiodarone | 1.27 (1.21–1.34) | |
| Diltiazem | 1.28 (1.13–1.46) | |
| Verapamil | 1.36 (1.03–1.80) | |
| Ticagrelor | 1.50 (1.20–1.87) | |
| Clarithromycin | 1.55 (1.14–2.11) | |
| 0.512Adjusted hazard ratio (log scale) |
Major bleeding with inhibitors, by NOAC (subgroup)
| Comparison | aHR (95% CI) | |
|---|---|---|
| Edoxaban | 1.24 (1.06–1.45) | |
| Rivaroxaban | 1.25 (1.16–1.34) | |
| Apixaban | 1.27 (1.16–1.39) | |
| Dabigatran · not significant | 1.07 (0.94–1.23) | |
| 0.512Adjusted hazard ratio (log scale) |
Original publication
Impact of P-glycoprotein and CYP3A4-interacting drugs on clinical outcomes in patients with atrial fibrillation using non-vitamin K antagonist oral anticoagulants: a nationwide cohort study. Eur Heart J Cardiovasc Pharmacother. Published 3 October 2023. doi:10.
Summarised from the published abstract; every number is checked against it