What are the advantages and disadvantages of using Eliquis (apixaban) post-operatively for a 68-year-old female with a history of breast cancer, who has been cancer-free for five years, undergoing knee replacement surgery?

Apixaban for VTE Prophylaxis After Knee Replacement in a 68-Year-Old Cancer Survivor

Apixaban 2.5 mg twice daily for 2 weeks post-operatively is strongly recommended for this patient, as it provides superior VTE risk reduction (9.3% absolute risk reduction) compared to standard prophylaxis after knee replacement, with no increased bleeding risk, and her remote cancer history (5 years disease-free) does not contraindicate its use. 1, 2

Advantages of Apixaban Post-Operatively

Efficacy in Orthopedic Surgery

• Apixaban demonstrated a 9.3% absolute risk reduction in VTE after total knee replacement (95% CI 5.8-12.7, p <0.001) compared to enoxaparin in the ADVANCE-2 trial, with VTE rates of 1.4% versus 3.9% 1, 2
• The American College of Chest Physicians recommends apixaban as a first-line choice for VTE prophylaxis after hip and knee replacement surgery, with a 64% relative risk reduction 2
• Extended prophylaxis (28-35 days) significantly decreases VTE risk in surgical patients, with the overall net benefit clearly favoring extended prophylaxis despite a small increase in bleeding risk 1

Practical Benefits

• Oral administration eliminates the need for daily subcutaneous injections, improving patient adherence and satisfaction compared to enoxaparin 1
• Fixed-dose regimen (2.5 mg twice daily) requires no weight-based adjustment or laboratory monitoring 3, 4
• Patient satisfaction with ease of medication administration was significantly higher with apixaban versus enoxaparin, though adherence rates were similar (84.8% vs 83.7%) 1

Safety Profile

• Apixaban showed numerically lower rates of major or clinically relevant non-major bleeding compared to enoxaparin in orthopedic trials 1, 2
• In the ADVANCE-2 trial, there was no increased risk of bleeding with apixaban versus enoxaparin after knee replacement 1
• Multiple elimination pathways (only 27% renal clearance) make it suitable for patients with mild-to-moderate renal impairment 2, 5

Disadvantages and Important Caveats

Bleeding Risk Considerations

• All anticoagulants carry inherent bleeding risk, with major bleeding rates approximately 2-4% across studies 3, 6
• Bleeding may be more difficult to stop and bruising more common while on apixaban 3
• The patient's concern about "increasing pain and inflammation" as a side effect is not substantiated in the evidence; however, bleeding into joints or surgical sites could manifest as increased pain 3

Specific Contraindications and Warnings

• Spinal or epidural hematoma risk: If the patient received spinal/epidural anesthesia during surgery, there is risk of spinal hematoma that can cause permanent paralysis; close monitoring is essential 3
• Contraindicated if the patient has active abnormal bleeding or severe allergic reaction history to apixaban 3
• Should be avoided in patients with history of deep vein thrombosis, pulmonary embolus, stroke, or transient ischemic attack during periods of prolonged immobilization 1

Drug Interactions

• Potent CYP3A4 inhibitors are contraindicated with apixaban as they increase plasma concentrations 5
• Increased bleeding risk when combined with aspirin, NSAIDs (which may be used for post-operative pain), other anticoagulants, SSRIs/SNRIs, or antiplatelet agents 3
• The patient should inform all healthcare providers about apixaban use before any procedures 3

Renal Function Monitoring

• Use with caution in severe renal impairment (CrCl 15-30 mL/min); avoid if CrCl <15 mL/min 2, 5
• Regular assessment of renal function is important, especially in elderly patients, as age-related decline may affect drug clearance 5

Cancer History Considerations

Relevance of Remote Breast Cancer

• The patient's 5-year cancer-free status means she is effectively not at increased cancer-related VTE risk for this surgical procedure 1
• The 2023 ASCO guidelines support apixaban use in cancer patients for VTE treatment and prophylaxis, but this applies to active cancer, not remote history 1
• Her breast cancer history does not contraindicate apixaban use; the concern would be if she had active gastrointestinal or genitourinary malignancies where mucosal bleeding risk is elevated 1

Post-Operative VTE Risk

• More than half of post-operative VTE events occur after hospital discharge, emphasizing the importance of extended prophylaxis 1
• The 2-week duration prescribed by the surgeon aligns with evidence supporting 28-day extended prophylaxis for high-risk orthopedic procedures 1

Clinical Implementation

Dosing and Duration

• Standard regimen: 2.5 mg orally twice daily for 12-35 days after knee replacement 1, 2, 3
• The 2-week (14-day) duration prescribed is reasonable, though evidence supports up to 28-35 days 1
• Take with or without food 3

Monitoring Requirements

• Baseline assessment of renal function, liver function, and bleeding risk factors before initiation 2, 5
• Patient education on bleeding signs: unusual bruising, prolonged bleeding, red/pink/brown urine, black stools, severe headaches, or unexplained pain/swelling 3
• Do not stop abruptly without physician consultation, as this increases thrombotic risk 3

When to Avoid or Use Caution

• Active bleeding or high bleeding risk conditions 3
• Severe renal impairment (CrCl <30 mL/min) 2
• Concomitant use of potent CYP3A4 inhibitors 5
• Antiphospholipid syndrome with positive triple antibody testing 3

Key Pitfall to Avoid

The most critical error would be discontinuing apixaban prematurely due to minor bruising or misattributing normal post-operative inflammation to the anticoagulant, as this would expose the patient to significantly increased VTE risk during the highest-risk period. 3 The surgeon's plan is evidence-based and appropriate for this patient's risk profile. 1, 2