How long should apixaban (Eliquis) be discontinued before surgery, considering the procedure’s bleeding risk and patient factors such as impaired renal function or advanced age?

Apixaban Discontinuation Before Surgery

For elective surgery, stop apixaban 1 day (24 hours) before low-to-moderate bleeding risk procedures and 2 days (48 hours) before high bleeding risk procedures in patients with normal renal function. 1

Bleeding Risk Classification

High bleeding risk procedures include: 1

• Cardiac surgery
• Intracranial or spinal surgery
• Major abdominal surgery (e.g., liver resection, pancreatic surgery)
• Major orthopedic surgery (hip/knee replacement)
• Procedures with duration >45 minutes in highly vascular organs
• Neuraxial anesthesia (spinal/epidural)

Low-to-moderate bleeding risk procedures include: 1

• Arthroscopy
• Colonoscopy with biopsy
• Laparoscopic cholecystectomy
• Abdominal hernia repair
• Coronary angiography (radial approach)
• Abdominal hysterectomy

Minimal bleeding risk procedures (can continue apixaban or hold morning dose only): 1

• Cataract surgery
• Minor dental procedures (extractions, fillings)
• Minor dermatologic procedures
• Pacemaker/ICD implantation

Standard Discontinuation Protocol

For patients with normal renal function (CrCl ≥80 mL/min): 1

• Low-to-moderate bleeding risk: Stop 1 day (24 hours) before surgery—this achieves 2-3 half-lives with 3-6% residual anticoagulant effect
• High bleeding risk: Stop 2 days (48 hours) before surgery—this achieves 4 half-lives with minimal residual effect

The PAUSE trial validated this approach in 1,257 apixaban patients, demonstrating arterial thromboembolism rates of 0.16% and major bleeding rates of 1.35%, confirming safety and efficacy. 1

Renal Impairment Adjustments

Apixaban elimination is 27% renal, requiring extended interruption in renal dysfunction: 2, 3

For CrCl 50-79 mL/min: 1

• Low-to-moderate bleeding risk: Stop 24 hours before (same as normal function)
• High bleeding risk: Stop 48 hours before (same as normal function)

For CrCl 30-49 mL/min: 1

• Low-to-moderate bleeding risk: Stop 24 hours before
• High bleeding risk: Stop 48 hours before

For CrCl 15-29 mL/min: 1

• Low-to-moderate bleeding risk: Stop 36 hours before
• High bleeding risk: Stop 48 hours before

Critical warning: Patients with severe chronic kidney disease can accumulate apixaban and experience catastrophic bleeding including pleural, pericardial, and intracranial hemorrhage. 2 Extended preoperative interruption is essential even if baseline renal function was acceptable, as declining function increases bleeding risk. 2

Special Considerations for Neuraxial Procedures

For spinal or epidural anesthesia, stop apixaban for a full 72 hours (3 days) regardless of renal function. 3 This extended duration accounts for the catastrophic consequences of epidural hematoma and associated lower limb paralysis, even though the absolute bleeding risk may be low. 1

Drug Interactions Requiring Extended Interruption

For patients taking concomitant P-gp inhibitors (dronedarone, amiodarone, verapamil): 1

• Consider adding an extra 24 hours of interruption, especially if thromboembolic risk is not very high (CHA2DS2-VASc <2-3)
• These medications reduce apixaban clearance and prolong its effect

FDA-Approved Discontinuation Guidance

The FDA label states apixaban should be discontinued: 4

• At least 48 hours prior to elective surgery with moderate or high bleeding risk
• At least 24 hours prior to elective surgery with low bleeding risk or where bleeding would be non-critical and easily controlled

This FDA guidance is more conservative than the ACCP guidelines but provides a safe default approach. 4

Bridging Anticoagulation

Do NOT use bridging with heparin or low molecular weight heparin during the interruption period. 1, 2, 4 The rapid offset and onset of apixaban obviates the need for bridging, and mixing two anticoagulants increases bleeding risk without reducing thromboembolism. 1 The PAUSE trial demonstrated this approach is safe without bridging. 1

Laboratory Monitoring Pitfalls

Standard coagulation tests (INR, aPTT) are unreliable for assessing apixaban effect and should NOT guide surgical timing. 2, 3 If measurement is needed, use DOAC-calibrated anti-factor Xa levels, though clinical utility remains uncertain. 1 A real-world study showed that 94% of patients achieved apixaban concentrations ≤30 ng/mL after discontinuation for at least 48 hours. 5

Postoperative Resumption

Resume apixaban at least 24 hours after low-to-moderate bleeding risk surgery once adequate hemostasis is established. 1, 2, 4

For high bleeding risk surgery, resume 48-72 hours postoperatively. 1, 2 Apixaban's rapid onset of action (peak effect 1-3 hours after intake) requires cautious administration to avoid bleeding if hemostasis is incomplete. 1, 2

Common Pitfalls to Avoid

• Never double the dose to compensate for a missed preoperative dose—this increases bleeding risk 4
• Avoid premature resumption after high-risk surgery—apixaban's rapid onset can precipitate major bleeding 2
• Do not rely on INR or aPTT for surgical clearance—these tests are inconsistent with apixaban 3
• Account for postoperative factors affecting absorption (bowel dysmotility, acid-suppressive therapy) after major abdominal surgery 2