Should I continue subcutaneous heparin and Eliquis (apixaban) in a patient with shortness of breath suspected of pulmonary embolism?

Should You Continue Both Eliquis and Subcutaneous Heparin for Suspected PE?

No—stop the subcutaneous heparin immediately and continue Eliquis (apixaban) alone at the correct acute PE dose of 10 mg twice daily for 7 days, then 5 mg twice daily. Dual anticoagulation with both agents simultaneously increases major bleeding risk without improving efficacy and is not supported by any guideline. 1, 2

Why Dual Anticoagulation Is Not Indicated

• Apixaban monotherapy is the preferred first-line treatment for acute PE in hemodynamically stable patients, eliminating the need for any parenteral anticoagulant lead-in. 1, 2
• The AMPLIFY trial (5,395 patients) demonstrated that apixaban 10 mg twice daily for 7 days followed by 5 mg twice daily was non-inferior to enoxaparin/warfarin for preventing recurrent VTE (2.3% vs 2.7%) and caused significantly less major bleeding (0.6% vs 1.8%; P<0.001). 3
• Subcutaneous heparin (LMWH or fondaparinux) is only required when transitioning to dabigatran or edoxaban, which mandate a 5-day parenteral lead-in; apixaban and rivaroxaban do not. 1, 2
• Continuing both agents concurrently exposes the patient to additive bleeding risk without any evidence of improved thrombus resolution or reduced recurrence. 4, 1

Correct Apixaban Dosing for Acute PE

• Days 1–7: Apixaban 10 mg orally twice daily. 1, 3
• Day 8 onward: Apixaban 5 mg orally twice daily for a minimum total duration of 3 months. 1, 2
• This single-drug regimen requires no INR monitoring and no aPTT checks. 1

When Parenteral Anticoagulation Is Actually Needed

• Hemodynamically unstable PE (systolic BP <90 mmHg or shock): switch to intravenous unfractionated heparin (80 IU/kg bolus, then 18 IU/kg/h infusion) and prepare for systemic thrombolysis with alteplase 100 mg over 2 hours. 4, 1, 2
• High clinical probability PE awaiting imaging confirmation: initiate LMWH or fondaparinux immediately, then transition to apixaban once PE is confirmed. 4, 2
• Severe renal impairment (CrCl <30 mL/min): apixaban is contraindicated; use unfractionated heparin bridged to warfarin (target INR 2.0–3.0). 1, 2
• Antiphospholipid antibody syndrome: apixaban is contraindicated; use LMWH bridged to warfarin indefinitely. 1, 2
• Pregnancy: apixaban is contraindicated; use therapeutic LMWH throughout gestation and for at least 6 weeks postpartum. 1, 2

Absolute Contraindications to Apixaban

• Creatinine clearance <25–30 mL/min. 1, 2
• Triple-positive antiphospholipid antibody syndrome. 1, 5
• Pregnancy or lactation. 1, 2
• Concurrent strong dual P-glycoprotein and CYP3A4 inhibitors (e.g., ritonavir, ketoconazole). 1

Duration of Anticoagulation

• Minimum 3 months for all PE cases, followed by mandatory reassessment at 3–6 months. 1, 2
• Provoked PE (major transient risk factor such as surgery, trauma, immobilization): stop after 3 months. 1, 2
• Unprovoked PE or recurrent VTE: continue indefinitely when bleeding risk is low-to-moderate; annual recurrence risk exceeds 5%. 1, 2
• After 6 months of full-dose therapy, consider dose reduction to apixaban 2.5 mg twice daily for extended prophylaxis. 1

Critical Pitfalls to Avoid

• Never combine apixaban with subcutaneous heparin for routine PE treatment; this is not evidence-based and increases bleeding. 1, 2
• Never use apixaban in severe renal impairment (<30 mL/min); switch to warfarin. 1, 2
• Never delay anticoagulation in high- or intermediate-probability PE while awaiting imaging; start LMWH or apixaban immediately. 4, 2
• Never assume apixaban failure without first confirming adherence, correct dosing, renal function, and absence of drug interactions. 5
• Never order D-dimer in high-probability PE; proceed directly to CTPA. 2

If PE Is Confirmed on Imaging

• Discontinue subcutaneous heparin immediately. 1
• Continue apixaban at 10 mg twice daily for 7 days, then 5 mg twice daily. 1, 3
• Reassess hemodynamic stability; if shock or hypotension develops, switch to unfractionated heparin and administer thrombolysis. 4, 1, 2
• Schedule follow-up at 3–6 months to screen for chronic thromboembolic pulmonary hypertension (CTEPH) and decide on anticoagulation duration. 1, 2