What is the best course of action for a patient with recurrent shortness of breath on Eliquis (apixaban) for Pulmonary Embolism (PE) prevention?

Management of Recurrent Shortness of Breath in a Patient on Apixaban for PE Prevention

For a patient with recurrent shortness of breath who had a negative stress test 3 months ago and is on Eliquis (apixaban) for PE prevention, the best course of action is to perform a formal diagnostic assessment with validated methods including CTPA or V/Q scan to rule out recurrent PE despite anticoagulation therapy.

Diagnostic Approach

Initial Assessment

• Evaluate clinical probability of PE using validated prediction rules or clinical judgment 1
• Assess for hemodynamic instability (blood pressure, heart rate, respiratory rate) 1
• Check oxygen saturation and arterial blood gases if hypoxemia is suspected 1

Diagnostic Testing Algorithm

1. High Clinical Suspicion: Proceed directly to imaging without D-dimer testing 1

   • D-dimer testing should not be performed in patients with high clinical probability as a normal result does not safely exclude PE 1

2. Low/Intermediate Clinical Suspicion:

   • Measure D-dimer levels using a highly sensitive assay 1
   • If D-dimer is negative, PE can be reasonably excluded 1
   • If D-dimer is positive, proceed to imaging 1

3. Imaging Options:

   • CTPA is the first-line imaging test for suspected PE 1
   • V/Q scan may be considered if CTPA is contraindicated or if chest radiograph is normal 1
   • Leg ultrasound can be useful if there are signs of DVT 1

Management Based on Diagnostic Results

If Recurrent PE is Confirmed:

1. Reassess Anticoagulation:

   • Verify patient adherence to apixaban therapy 2
   • Check if the patient is taking the correct dose (10 mg twice daily for 7 days followed by 5 mg twice daily for treatment, or 2.5 mg twice daily for secondary prevention) 3
   • Consider therapeutic drug monitoring if available 2

2. Treatment Options:

   • If PE recurred despite proper adherence to apixaban:
     • Consider switching to a different anticoagulant class 2
     • Consider IVC filter placement if recurrent PE despite therapeutic anticoagulation 1, 2
     • Evaluate for underlying conditions (cancer, antiphospholipid syndrome) 1, 2

If PE is Excluded:

1. Alternative Diagnoses:

   • Consider cardiac causes (given negative stress test, focus on heart failure, valvular disease)
   • Evaluate for pulmonary causes (COPD exacerbation, asthma, interstitial lung disease)
   • Consider post-PE syndrome or chronic thromboembolic pulmonary hypertension (CTEPH) 1

2. Further Evaluation:

   • Echocardiography to assess for right ventricular dysfunction or pulmonary hypertension 1, 2
   • Pulmonary function tests to evaluate for obstructive or restrictive lung disease
   • Consider referral to a pulmonary hypertension/CTEPH expert center if symptoms persist with mismatched perfusion defects beyond 3 months after initial PE 1

Special Considerations

Monitoring and Follow-up

• Routinely re-evaluate patients 3-6 months after acute PE 1, 2
• Assess for signs of post-thrombotic syndrome or CTEPH 1
• Regularly reassess drug tolerance, adherence, renal/hepatic function, and bleeding risk 1, 2

Pitfalls to Avoid

• Do not discontinue anticoagulation without definitive evidence that PE is not the cause of symptoms 3
• Do not assume that anticoagulation prevents all recurrent PE events - breakthrough PE can occur despite appropriate therapy 2
• Do not attribute symptoms to anxiety or deconditioning without thorough evaluation 1
• Do not overlook the possibility of CTEPH in patients with persistent symptoms after PE 1

Conclusion

Recurrent shortness of breath in a patient on anticoagulation for PE prevention requires thorough investigation to determine if it represents recurrent PE despite therapy or an alternative diagnosis. A systematic approach with appropriate imaging is essential to guide management decisions and improve outcomes.