What is the preferred choice between Aspirin (acetylsalicylic acid) and Eliquis (apixaban) for Venous Thromboembolism (VTE) prophylaxis after hip surgery?

Apixaban (Eliquis) is Superior to Aspirin for VTE Prophylaxis After Hip Surgery

For VTE prophylaxis after hip replacement surgery, apixaban 2.5 mg twice daily is the preferred choice over aspirin, based on superior efficacy demonstrated in large randomized trials and FDA approval for this specific indication. 1

Evidence Supporting Apixaban as First-Line Choice

FDA-Approved Indication and Dosing

• Apixaban is FDA-approved specifically for prophylaxis of deep vein thrombosis following hip or knee replacement surgery 1
• The recommended dose is 2.5 mg orally twice daily, initiated 12-24 hours after surgery 1
• For hip replacement surgery specifically, the recommended duration is 35 days 1

Superior Efficacy Data from ADVANCE Trials

• The ADVANCE-3 trial demonstrated apixaban's superiority over enoxaparin (the gold standard) in patients undergoing hip arthroplasty, with VTE rates of 1.4% versus 3.9% (RR 0.36; 95% CI 0.22-0.54; P<0.001) 2
• This represents a 64% relative risk reduction compared to standard anticoagulation 2
• Apixaban showed numerically lower rates of major or clinically relevant nonmajor bleeding compared to enoxaparin, though this only reached statistical significance in some trials 2

Limited Evidence for Aspirin in Primary Prophylaxis

• Aspirin has been studied primarily for extended VTE prophylaxis after initial treatment with LMWH, not as primary prophylaxis 2
• One study found aspirin was noninferior to LMWH for extended prophylaxis only after patients had already received 10 days of LMWH 2
• The WARFASA and ASPIRE trials evaluated aspirin for secondary prevention (preventing recurrence after established VTE), not primary prophylaxis after surgery 2

Clinical Decision Algorithm

When to Use Apixaban (Preferred)

• All patients undergoing hip replacement surgery without contraindications 1
• Start 12-24 hours post-surgery when hemostasis is established 1
• Continue for 35 days 1
• Requires creatinine clearance >15 mL/min 1

Contraindications to Apixaban

• Active pathological bleeding 1
• Severe hepatic impairment with coagulopathy 1
• Concomitant use of potent CYP3A4 and P-glycoprotein inhibitors (ketoconazole, ritonavir) 2
• Planned neuraxial anesthesia within 48 hours (high bleeding risk procedures) 1

When Aspirin Might Be Considered (Second-Line)

• Patients with contraindications to all anticoagulants 2
• As extended prophylaxis after completing initial 10-14 days of therapeutic anticoagulation 2
• Patients with prohibitive bleeding risk where even prophylactic anticoagulation is contraindicated 2

Important Safety Considerations

Bleeding Risk Management

• Major bleeding rates with apixaban for VTE prophylaxis are low and comparable to or lower than enoxaparin 2, 3
• Discontinue apixaban at least 48 hours before elective surgery with moderate-to-high bleeding risk 1
• For low bleeding risk procedures, discontinue 24 hours prior 1
• Bridging anticoagulation is not generally required during the 24-48 hour interruption 1

Neuraxial Anesthesia Warning

• Epidural or spinal hematomas may occur with neuraxial anesthesia, potentially causing permanent paralysis 1
• Risk factors include indwelling epidural catheters, concomitant NSAIDs or antiplatelet agents, and history of spinal procedures 1
• Monitor frequently for neurological impairment 1

Renal Function Monitoring

• Apixaban has multiple elimination pathways with only 27% renal clearance, making it suitable for patients with mild-to-moderate renal impairment 4
• Use with caution in severe renal impairment (CrCl 15-30 mL/min); avoid if CrCl <15 mL/min 5

Common Pitfalls to Avoid

• Do not use aspirin as primary prophylaxis immediately after hip surgery - it lacks evidence and FDA approval for this indication 2, 1
• Do not start apixaban too early - wait 12-24 hours post-surgery to ensure hemostasis 1
• Do not stop apixaban prematurely - complete the full 35-day course unless contraindicated, as premature discontinuation increases thrombotic risk 1
• Do not double dose if a dose is missed - take as soon as remembered on the same day and resume twice-daily schedule 1
• Do not combine with other anticoagulants unless specifically bridging therapy, which is rarely needed 1

Comparative Context with Other Anticoagulants

While rivaroxaban (another direct factor Xa inhibitor) also showed efficacy in the RECORD trials for hip arthroplasty 2, apixaban demonstrated superior efficacy to enoxaparin in head-to-head trials 2 and has a well-established safety profile with lower bleeding rates than warfarin-based regimens 2. The choice between apixaban and rivaroxaban may depend on institutional protocols, but both are superior to aspirin for primary prophylaxis 6.