What is the workup for Eliquis (apixaban) failure?

Workup for Apixaban (Eliquis) Failure

When a patient experiences a thromboembolic event despite therapeutic apixaban, perform a thorough diagnostic evaluation to identify reversible causes including non-adherence, inadequate dosing, competing stroke mechanisms, and cardiovascular risk factors before considering any anticoagulant switch. 1

Initial Diagnostic Assessment

Confirm True Anticoagulation Failure

• Verify medication adherence through patient interview, pharmacy refill records, and pill counts, as non-adherence is a common cause of apparent anticoagulation failure 1
• Assess dosing appropriateness by reviewing current dose against indication, renal function (using Cockcroft-Gault formula), body weight, and age to ensure the patient is on the correct dose (5 mg vs 2.5 mg twice daily) 2
• Measure apixaban drug levels if available, as laboratory measurement can reveal subtherapeutic anticoagulation or non-adherence 1

Evaluate Alternative Stroke Mechanisms

The European Society of Cardiology emphasizes that one-third of AF patients presenting with ischemic stroke are already on anticoagulation, often due to competing non-cardioembolic mechanisms 1:

• Large artery atherosclerosis: Obtain carotid duplex ultrasound and consider CT or MR angiography of cerebral vessels 1
• Small vessel disease: Review brain imaging for lacunar infarcts and white matter disease 1
• Assess cardiovascular risk factors including hypertension, diabetes, hyperlipidemia, and smoking, as patients with breakthrough events have higher prevalence of these factors 1

Laboratory and Imaging Workup

• Complete blood count to assess for thrombocytosis or polycythemia that could increase thrombotic risk 1
• Renal function assessment (serum creatinine and calculated CrCl) as severe renal impairment (CrCl <15 mL/min) is a relative contraindication to apixaban and may alter drug clearance 2
• Echocardiography to evaluate for structural heart disease, valvular abnormalities, or intracardiac thrombus 1
• Consider hypercoagulability workup if clinically indicated (antiphospholipid antibodies, malignancy screening) particularly in younger patients or those with unprovoked events 1

Management Decisions

Do NOT Routinely Switch Anticoagulants

The European Society of Cardiology explicitly recommends against switching from one DOAC to another, or from a DOAC to a VKA, without a clear indication, as this has no proven efficacy for preventing recurrent embolic stroke. 1

Address Modifiable Risk Factors

• Optimize blood pressure control to target <130/80 mmHg 1
• Intensify lipid management with high-intensity statin therapy 1
• Ensure glycemic control in diabetic patients 1
• Smoking cessation and lifestyle modifications 1

When Switching May Be Considered

Consider alternative anticoagulation strategies only if 2:

• Documented non-adherence to twice-daily dosing (consider once-daily rivaroxaban or edoxaban)
• Severe renal impairment develops (CrCl <15 mL/min) requiring switch to warfarin with careful INR monitoring 2
• Recurrent bleeding complications making apixaban continuation unsafe 2

Do NOT Add Antiplatelet Therapy

Adding antiplatelet treatment to anticoagulation is not recommended in AF patients to prevent recurrent embolic stroke, as it increases bleeding risk without proven benefit. 1

Common Pitfalls to Avoid

• Avoid reflexive switching between DOACs after a breakthrough event, as there is no evidence this improves outcomes and may introduce new risks during the transition period 1
• Do not combine aspirin with apixaban for secondary stroke prevention, as this significantly increases major bleeding without reducing recurrent stroke 1
• Ensure proper dose reduction criteria are met (age ≥80, weight ≤60 kg, or creatinine ≥1.5 mg/dL with at least 2 of 3 criteria) to avoid both under- and over-anticoagulation 3
• Recognize that purely ischemic strokes occurred at similar rates between apixaban and warfarin in ARISTOTLE, suggesting some events are unavoidable regardless of anticoagulant choice 3

Alternative Strategies for Refractory Cases

If anticoagulation is deemed too high-risk after recurrent events 2:

• Left atrial appendage occlusion may be considered as a non-pharmacologic alternative 1
• Aspirin 81-100 mg daily provides modest protection if anticoagulation must be discontinued, though significantly inferior to continued anticoagulation 2