How many days should Apixaban (Apixaban) be held prior to surgery in a patient with impaired renal function or normal renal function undergoing high or low-risk procedures?

Apixaban Preoperative Discontinuation

Hold apixaban for 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, 2

Discontinuation Based on Bleeding Risk

Low-to-Moderate Bleeding Risk Procedures

• Stop apixaban 1 day (24 hours) before surgery, corresponding to 2-3 half-lives and achieving minimal residual anticoagulant effect 1, 2
• Examples include arthroscopy, laparoscopic cholecystectomy, abdominal hernia repair, colonoscopy with biopsy, and coronary angiography 1, 2
• This timing allows for approximately 3-6% residual anticoagulant effect at the time of procedure 3

High Bleeding Risk Procedures

• Stop apixaban 2 days (48 hours) before surgery, corresponding to 4-5 half-lives and achieving minimal residual anticoagulant effect 1, 2
• Examples include cardiac surgery, intracranial/spinal surgery, major abdominal surgery, and surgery in highly vascular organs 1, 3
• This extended interruption ensures minimal anticoagulant activity at the time of the procedure 1

Neuraxial Procedures (Special Consideration)

• Stop apixaban 3 days (72 hours) before spinal or epidural anesthesia, even in patients with normal renal function 4, 2
• This longer discontinuation period is mandatory due to the catastrophic risk of epidural hematoma and associated lower limb paralysis 1, 4

Renal Function Considerations

Renal function assessment is mandatory before determining the discontinuation timeline, as apixaban has 25-27% renal clearance 4, 3

Patients with Moderate Renal Impairment (CrCl 30-50 mL/min)

• Stop apixaban 3 days before low-to-moderate bleeding risk procedures 3
• Stop apixaban 4 days before high bleeding risk procedures 3
• Extended interruption is essential because impaired renal function significantly prolongs apixaban elimination 4, 3

Patients with Severe Renal Impairment (CrCl <30 mL/min)

• Consider 3+ days of preoperative cessation, as these patients can accumulate apixaban and experience catastrophic bleeding 2, 3

FDA-Approved Guidance

The FDA label states: "Apixaban tablets should be discontinued at least 48 hours prior to elective surgery or invasive procedures with a moderate or high risk of unacceptable or clinically significant bleeding" and "at least 24 hours prior to elective surgery or invasive procedures with a low risk of bleeding" 5

Bridging Anticoagulation

Do not use bridging anticoagulation during the interruption period 2, 3

• Bridging with heparin or low molecular weight heparin increases major bleeding risk without reducing stroke or systemic embolism 3
• The rapid offset and rapid onset of action of apixaban obviates the need for heparin bridging 1

Postoperative Resumption

Low Bleeding Risk Surgery

• Resume apixaban at least 24 hours after surgery once adequate hemostasis is established 1, 2
• Full therapeutic dose (5 mg twice daily) can be resumed at this time 2

High Bleeding Risk Surgery

• Resume apixaban 48-72 hours after surgery once adequate hemostasis is established 1, 2
• Consider reduced dose (2.5 mg twice daily) for the first 2-3 days in high thrombotic risk patients before advancing to full therapeutic dosing 2, 3

Critical Pitfalls to Avoid

• Do not use INR or aPTT to guide timing, as apixaban's effect on these tests is inconsistent and unreliable for surgical clearance 4, 2
• Do not resume therapeutic-dose apixaban in the presence of an epidural catheter 2
• Avoid premature resumption after high-risk surgery, as apixaban has rapid onset of action (peak effect 1-3 hours) and can precipitate major bleeding if hemostasis is incomplete 1, 3
• Account for factors affecting drug absorption after major abdominal surgery, such as postoperative bowel dysmotility and acid-suppressive therapy 3

Real-World Evidence

A prospective observational study of 111 patients demonstrated that apixaban discontinuation for at least 48 hours before a procedure resulted in clinically insignificant anticoagulation (94% had concentrations ≤30 ng/mL), with only one clinically significant nonmajor bleeding event reported 6