How should a patient with a history of pulmonary embolism (PE) on Eliquis (apixaban) be evaluated for recurrent PE or other causes of shortness of breath, and is a CT chest angiography warranted?

Evaluation of Shortness of Breath in a Patient with Prior PE on Eliquis

In a patient with prior pulmonary embolism on Eliquis presenting with new shortness of breath, you should NOT automatically proceed to CT chest angiography—instead, use a structured clinical probability assessment followed by D-dimer testing (if appropriate) to guide imaging decisions, and strongly consider lower-extremity venous ultrasonography as an alternative first-line test to reduce cumulative radiation exposure. 1, 2

Initial Clinical Assessment

Assess clinical probability using a validated decision rule (Wells score or Geneva score) or clinical gestalt before ordering any imaging. 2, 3 This is mandatory and must be documented. The key is determining whether this represents:

• Recurrent PE
• Residual/chronic thromboembolic disease
• An alternative diagnosis (cardiac, pulmonary parenchymal disease, etc.)

Critical clinical features to evaluate:

• Respiratory rate >20/min (most PE patients are tachypneic) 2
• Oxygen saturation (hypoxemia supports PE) 2
• Pleuritic chest pain vs. other chest pain patterns 2
• Unilateral leg swelling (suggests DVT source) 2
• Recent immobility, surgery, or trauma 2
• Comparison to prior PE symptoms (are current symptoms similar?) 1

Important caveat: In the absence of tachypnea (>20/min), pleuritic pain, AND arterial hypoxemia, PE can be excluded without further testing. 2

Diagnostic Algorithm Based on Clinical Probability

Low or Intermediate Probability Patients

Proceed with D-dimer testing FIRST before any imaging. 1, 2, 3 This is critical to avoid unnecessary CT scans. 1

• Use age-adjusted D-dimer thresholds for patients >50 years: age × 10 ng/mL (rather than the standard 500 ng/mL cutoff). 1 This maintains sensitivity >97% while significantly improving specificity (from 14.7% to 35.2% in patients >80 years). 1

• If D-dimer is negative: PE is excluded—no imaging needed. 2, 3 The negative predictive value is >98% in this population. 3

• If D-dimer is elevated: Proceed to imaging (see below for imaging strategy). 2, 3

High Probability Patients

Proceed directly to imaging—D-dimer testing is not useful in this population due to low negative predictive value. 1, 3

Imaging Strategy: Avoiding Repeated CT Exposure

This is a critical decision point for patients with prior PE history. The American College of Physicians specifically addresses patients like yours who may have had multiple prior CTs—5% of PE patients undergo 5 or more CTs within 5 years. 1

First-Line Imaging Options (in order of preference for recurrent evaluation):

1. Lower-Extremity Venous Ultrasonography

• Strongly recommended as initial test for patients with history of multiple CTs. 1, 2
• If DVT is identified, this establishes need for anticoagulation without CT exposure. 1
• Particularly useful if patient has lower-extremity symptoms. 1
• The British Thoracic Society specifically recommends leg vein imaging as first-line for patients with PE history presenting with chest symptoms. 2

2. V/Q Scanning (Ventilation-Perfusion Scan)

• Preferred alternative to CT for patients with prior radiation exposure. 1
• Important limitation: Not useful if patient has COPD, pneumonia, or pulmonary edema. 1
• For suspected recurrent/acute PE: V/Q-SPECT/CT has comparable accuracy to CTA with highest specificity. 1
• For chronic/residual PE: V/Q scanning is the initial diagnostic test of choice with sensitivity 96-97.4% and specificity 90-95% (superior to CTA which has only 51% sensitivity for chronic PE). 1

3. CT Pulmonary Angiography (CTPA)

• Reserve for patients where V/Q scanning cannot be performed or when lower-extremity ultrasound is negative but suspicion remains high. 1
• The ACR Appropriateness Criteria (2025) confirms CTPA remains useful for suspected recurrent/residual PE, but emphasizes the radiation burden concern. 1
• Should be performed within 24 hours for non-massive PE. 3

Special Considerations for Patients on Eliquis

Review medication adherence and potential drug interactions. 4 Apixaban can fail in the presence of:

• Strong CYP3A4 inducers (carbamazepine, phenytoin, rifampin, St. John's wort) 5, 4
• Malignancy (which increases VTE risk independent of anticoagulation) 4

Assess adequacy of current anticoagulation:

• Is the patient on the correct dose? (5 mg twice daily for most; 2.5 mg twice daily if ≥2 of: age ≥80, weight ≤60 kg, creatinine ≥1.5 mg/dL) 5
• Has the patient missed doses? 5
• Any recent dose interruption for procedures? 5

Alternative Diagnoses to Consider

Do not assume recurrent PE automatically. 2 Shortness of breath in a patient with prior PE can represent:

• Post-PE syndrome with functional limitation 1
• Chronic thromboembolic pulmonary hypertension (CTEPH)—occurs in 0.6-8.2% of PE patients 1
• Cardiac dysfunction (right ventricular impairment from prior PE) 1
• Deconditioning
• Concurrent cardiac or pulmonary disease unrelated to PE

Obtain baseline chest X-ray, ECG, and arterial blood gas to help identify alternative diagnoses. 2

Common Pitfalls to Avoid

1. Reflexively ordering CT without clinical probability assessment—this leads to overuse of imaging and radiation exposure. 1, 3

2. Ordering D-dimer in high-probability patients—it won't change management and delays definitive imaging. 1, 3

3. Using standard D-dimer cutoff (500 ng/mL) in elderly patients—this causes false positives and unnecessary imaging. 1

4. Ignoring lower-extremity ultrasonography as a first-line option—this is specifically recommended for patients with PE history to reduce radiation. 1, 2

5. Assuming therapeutic anticoagulation excludes recurrent PE—anticoagulation failure occurs, especially with drug interactions or malignancy. 4

Management if PE is Confirmed

If recurrent PE is diagnosed despite therapeutic Eliquis:

• Investigate for anticoagulation failure (drug interactions, malignancy, thrombophilia) 4
• Consider switching anticoagulant class 5
• Evaluate for underlying malignancy if not already done 3
• Assess for chronic thromboembolic disease if symptoms persist >3 months 1