Should a patient with polycythemia vera and a history of ischemic stroke receive low‑dose aspirin for stroke prevention?

Aspirin for Stroke Prevention in Polycythemia Vera

Yes, a patient with polycythemia vera and a history of ischemic stroke should receive low-dose aspirin 100 mg daily for stroke prevention, as this regimen addresses both the underlying thrombotic risk from polycythemia vera and provides secondary stroke prevention. 1, 2

Evidence-Based Rationale

Dual Indication for Aspirin Therapy

This patient has two distinct but overlapping indications for aspirin:

• Polycythemia vera: The landmark ECLAP trial demonstrated that aspirin 100 mg daily significantly reduces the combined endpoint of nonfatal MI, nonfatal stroke, pulmonary embolism, major venous thrombosis, or death from cardiovascular causes (RR 0.40; 95% CI 0.18-0.91; P=0.03) in polycythemia vera patients without substantially increasing bleeding risk. 2, 1

• Secondary stroke prevention: For patients with prior ischemic stroke, aspirin 75-100 mg daily is recommended for long-term secondary prevention, providing equivalent stroke risk reduction compared to higher doses while minimizing bleeding complications. 3, 4

Optimal Dosing Strategy

The recommended dose is 100 mg once daily, which satisfies both the polycythemia vera indication (where 100 mg is the established effective dose) and the secondary stroke prevention indication (where 75-100 mg is recommended). 3, 1, 5

• The American College of Chest Physicians guidelines specifically identify 100 mg as the lowest effective daily dose for polycythemia vera, while 50 mg is sufficient for transient ischemic attack and ischemic stroke prevention. 3

• Using 100 mg daily addresses the higher thrombotic burden in polycythemia vera while remaining within the safe and effective range for stroke prevention. 1, 5

Safety Profile

The ECLAP trial found no significant increase in major bleeding episodes with aspirin compared to placebo in polycythemia vera patients (RR 1.62; 95% CI 0.27-9.71). 2, 1

Critical contraindications to assess before initiating aspirin include:

• Acquired von Willebrand syndrome, particularly with extreme thrombocytosis >1,500 × 10⁹/L 1
• Active bleeding or documented high bleeding risk 1
• History of aspirin allergy or hypersensitivity 1

Integration with Comprehensive Management

Aspirin must be combined with other essential therapies for polycythemia vera:

• Phlebotomy: Maintain hematocrit <45% in all patients to reduce hyperviscosity-related thrombotic risk. 1, 6

• Cytoreductive therapy: If the patient is high-risk (age >60 years or prior thrombosis—which this patient has), add hydroxyurea or interferon-alpha in addition to aspirin and phlebotomy. 1

• Cardiovascular risk factor modification: Aggressively manage hypertension (target <140/90 mmHg, or <130/80 mmHg if tolerated), diabetes, hyperlipidemia, and ensure smoking cessation. 1, 4

Monitoring Considerations

One-third of polycythemia vera patients on low-dose aspirin display less-than-maximal inhibition of platelet thromboxane A₂ production, particularly those with higher platelet counts. 7

• If thrombotic events occur despite aspirin therapy, consider measuring serum thromboxane B₂ to assess adequacy of platelet inhibition. 7

• For patients with inadequate platelet inhibition on once-daily dosing, twice-daily aspirin (50 mg bid) may achieve complete inhibition, though this requires individualized assessment. 7

Alternative Antiplatelet Considerations

While aspirin is the cornerstone therapy, the American College of Chest Physicians guidelines for noncardioembolic stroke also recommend clopidogrel (75 mg once daily) or aspirin/extended-release dipyridamole (25 mg/200 mg bid) as acceptable alternatives, with clopidogrel or aspirin/dipyridamole suggested over aspirin alone for stroke prevention. 3

However, for polycythemia vera specifically, aspirin remains the evidence-based first-line antiplatelet agent, as the ECLAP trial established its efficacy in this population. 2, 1 If aspirin is contraindicated due to documented allergy, substitute clopidogrel 75 mg daily. 4

Long-Term Management

Aspirin should be continued indefinitely unless contraindications develop, as both polycythemia vera and prior stroke confer lifelong thrombotic risk. 1 Regular monitoring for occult gastrointestinal bleeding is prudent, particularly in elderly patients, with periodic hemoglobin/hematocrit and stool guaiac testing. 4