How long should apixaban 5 mg twice daily be stopped before carotid endarterectomy?

Apixaban Discontinuation Before Carotid Endarterectomy

Stop apixaban 5 mg twice daily at least 48 hours (2 days) before carotid endarterectomy in patients with normal renal function, which corresponds to skipping 2 doses and allows approximately 4 half-lives to elapse, resulting in minimal residual anticoagulant effect at the time of surgery. 1

Timing Based on Renal Function

Normal Renal Function (CrCl >50 mL/min)

• Discontinue apixaban 48 hours (2 days) before surgery, which means the last dose should be taken 2 days prior to the procedure 2, 3, 1
• This timing allows for approximately 4 half-lives to expire, resulting in only 6% residual anticoagulant effect at the time of surgery 3
• The FDA label explicitly states apixaban should be discontinued at least 48 hours prior to elective surgery or invasive procedures with moderate or high risk of bleeding 1

Impaired Renal Function (CrCl 30-50 mL/min)

• Extend the discontinuation period to 72 hours (3 days) before surgery 2, 3, 4
• Apixaban has 25% renal clearance, and reduced kidney function prolongs drug elimination 3, 5
• Always calculate creatinine clearance using the Cockcroft-Gault formula before determining the hold duration 2, 3

Classification of Carotid Endarterectomy

Carotid endarterectomy is classified as a high bleeding risk procedure because:

• It involves major vascular surgery where surgical hemostasis must be performed safely 2
• There is potential for significant bleeding that cannot be easily controlled 3
• The procedure requires a window without anticoagulant effect 2

Drug Interaction Considerations

• Assess for P-glycoprotein (P-gp) and CYP3A4 inhibitors that may prolong apixaban clearance 2, 3, 4
• If the patient is taking strong P-gp or CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, ritonavir), consider extending the hold period by an additional 24 hours 4
• Common P-gp inhibitors include verapamil, amiodarone, and clarithromycin 2

Bridging Anticoagulation

Do not use heparin bridging therapy before carotid endarterectomy 2, 3, 4

• Preoperative bridging with unfractionated heparin (UFH) or low-molecular-weight heparin (LMWH) is not recommended 2, 3
• Bridging anticoagulation increases major bleeding risk without reducing stroke or systemic embolism 3, 4
• The FDA label states bridging during the 24-48 hours after stopping apixaban is not generally required 1
• Reserve bridging only for very high thrombotic risk patients, determined by multidisciplinary discussion 3

Postoperative Resumption

• Resume apixaban at least 6 hours after surgery once adequate hemostasis is confirmed 2, 3
• For high bleeding risk procedures like carotid endarterectomy, consider delaying resumption to 48-72 hours postoperatively 3, 4
• The FDA label recommends restarting apixaban after surgical procedures as soon as adequate hemostasis has been established 1

Evidence Supporting 48-Hour Hold

A prospective cohort study demonstrated that apixaban discontinuation for at least 48 hours before surgery resulted in clinically insignificant anticoagulation, with 94% of patients achieving apixaban concentrations ≤30 ng/mL 6

• The median time between last dose and presurgery blood sampling was 76 hours for those achieving safe concentrations 6
• Only one patient experienced clinically significant nonmajor bleeding at 1 week postsurgery 6

Common Pitfalls to Avoid

• Do not assume 24 hours is sufficient—carotid endarterectomy requires at least 48 hours for patients with normal renal function 3, 4, 1
• Do not forget to assess renal function—impaired clearance necessitates 72-hour hold times 2, 3, 4
• Do not bridge with heparin routinely—this increases bleeding without benefit 2, 3, 4
• Do not resume apixaban too early—confirm hemostasis before restarting anticoagulation 3, 1
• Do not ignore drug interactions—P-gp and CYP3A4 inhibitors require extended hold periods 2, 3, 4

Practical Algorithm

1. Calculate creatinine clearance using Cockcroft-Gault formula 2, 3
2. Review medication list for P-gp and CYP3A4 inhibitors 2, 3, 4
3. Determine hold duration:
   • CrCl >50 mL/min without drug interactions: 48 hours 2, 3, 1
   • CrCl 30-50 mL/min: 72 hours 2, 3, 4
   • Presence of P-gp/CYP3A4 inhibitors: Add 24 hours 4
4. Do not bridge with heparin 2, 3, 4
5. Resume apixaban 48-72 hours postoperatively once hemostasis confirmed 3, 4