How long should apixaban (Eliquis) be held before orthopedic surgery?

How Long to Hold Eliquis for Orthopedic Surgery

For most orthopedic surgeries, hold apixaban (Eliquis) for 48 hours (2 days) prior to the procedure if the patient has normal renal function (CrCl >50 mL/min). 1

Standard Preoperative Management

The FDA label for Eliquis provides clear guidance that directly applies to orthopedic surgery 1:

• Moderate to high bleeding risk procedures: Discontinue at least 48 hours before surgery
• Low bleeding risk procedures: Discontinue at least 24 hours before surgery

Most orthopedic surgeries (hip/knee replacements, spine surgery) fall into the moderate-to-high bleeding risk category, requiring the 48-hour hold.

Evidence Supporting the 48-Hour Hold

The PAUSE trial (2022), a large prospective study of 3,007 patients, validated this approach 2. For high-bleed-risk surgeries, apixaban was held for 2 days before and 2 days after surgery (4 days total interruption), resulting in:

• 30-day arterial thromboembolism rate: 0.16% (95% CI: 0-0.48)
• Major bleeding rate: 1.35% (95% CI: 0-2.0)

A 2022 observational study (ADIOS) confirmed that 48-hour cessation resulted in clinically insignificant anticoagulation levels in 94% of patients, with median time to surgery of 76 hours 3.

Adjust for Renal Function

Critical caveat: The 48-hour rule assumes normal renal function. You must adjust based on creatinine clearance:

• CrCl >50 mL/min: Hold for 48 hours (2 days)
• CrCl 30-50 mL/min: Hold for 72-96 hours (3-4 days) 4
• CrCl <30 mL/min: Hold for 96-120 hours (4-5 days) 2, 4

The French GIHP guidelines (2017) recommend up to 5 days for very high hemorrhagic risk procedures like spinal surgery or neuraxial anesthesia in patients with renal impairment 4.

Additional Risk Factors Requiring Longer Hold

Extend the interruption period beyond 48 hours if the patient has:

• Drug interactions: Taking P-glycoprotein or CYP3A4 inhibitors (ketoconazole, itraconazole, ritonavir) that impair apixaban clearance 2
• Advanced age: Patients >80 years may have prolonged drug half-life 5
• Hepatic impairment: Reduced drug metabolism 2

No Bridging Required

Do not use heparin bridging during the 48-hour interruption period for most patients 1. The FDA label explicitly states "bridging anticoagulation during the 24 to 48 hours after stopping ELIQUIS and prior to the intervention is not generally required" 1. The PAUSE trial confirmed excellent outcomes without bridging 2.

Practical Algorithm

1. Calculate CrCl using Cockcroft-Gault formula
2. Assess bleeding risk of the specific orthopedic procedure (most are high-risk)
3. Check for drug interactions (P-gp/CYP3A4 inhibitors)
4. Determine hold time:
   • Normal renal function (CrCl >50): 48 hours
   • Mild impairment (CrCl 30-50): 72-96 hours
   • Severe impairment (CrCl <30): 96-120 hours
5. No bridging unless extremely high thrombotic risk
6. Resume 12-24 hours post-surgery once hemostasis achieved 1

Special Consideration for Neuraxial Anesthesia

For spinal or epidural anesthesia, the French guidelines strongly recommend against performing the procedure if there is any possibility of residual apixaban effect, particularly in elderly patients or those with renal impairment 4. This reinforces the need for adequate drug clearance before orthopedic procedures requiring neuraxial techniques.

When to Consider Drug Level Testing

In urgent orthopedic cases (e.g., hip fracture requiring surgery within 24 hours), consider measuring apixaban-calibrated anti-factor Xa levels if available 2. However, this is not routinely necessary for elective procedures when proper timing is followed.