Is epoetin safe with apixaban and aspirin?

Safety of Epoetin with Apixaban and Aspirin

Epoetin should be used with extreme caution in patients taking apixaban and aspirin due to significantly increased risk of thromboembolic events.

Thromboembolic Risk Assessment

• Erythropoiesis-stimulating agents (ESAs) like epoetin are associated with an increased risk of thromboembolism as demonstrated by randomized clinical trials and systematic reviews 1.
• The combination of epoetin with anticoagulants (apixaban) and antiplatelet agents (aspirin) requires careful clinical judgment due to competing risks:
  • Epoetin increases thromboembolism risk 1
  • Apixaban and aspirin together significantly increase bleeding risk 2

Specific Risk Factors to Consider

• The patient is on both apixaban and aspirin, which already increases bleeding risk significantly:

  • In clinical trials, concomitant use of apixaban and aspirin increased bleeding risk from 1.8% to 3.4% per year 2
  • The APPRAISE-2 trial showed ISTH major bleeding was 2.8% per year with apixaban versus 0.6% with placebo in patients on single antiplatelet therapy 2

• Additional risk factors for thromboembolism in this patient include:

  • Multiple medications that may interact with anticoagulation therapy 1
  • Presence of atrial flutter (indicated by apixaban prescription) 2
  • Rheumatoid arthritis (indicated by hydroxychloroquine and Rinvoq) 1

Decision Algorithm for Epoetin Use

1. Assess baseline hemoglobin level:

   • If Hb < 10 g/dL and patient is symptomatic, consider epoetin with extreme caution 1
   • If Hb > 10 g/dL, avoid epoetin due to unfavorable risk-benefit ratio 1

2. Consider alternative treatments first:

   • Evaluate and treat underlying causes of anemia (iron deficiency, etc.) 1
   • Consider RBC transfusion for severe symptomatic anemia instead of ESAs 1

3. If epoetin is deemed necessary:

   • Consider temporary discontinuation or dose reduction of aspirin if clinically appropriate 2
   • Monitor hemoglobin levels closely, targeting no higher than 12 g/dL 1
   • Discontinue epoetin if no response after 6-8 weeks 1
   • Monitor for signs of thromboembolism (swelling, pain, shortness of breath) 1

Important Considerations and Precautions

• There are no data regarding the concomitant use of anticoagulants or aspirin to modulate thromboembolic risk with epoetin 1
• The number needed to harm (NNH) for thromboembolic events with epoetin is approximately 75 patients for those with a baseline risk of 2% 1
• The risk increases dramatically (NNH of 7.5) for patients with a baseline risk of 20% 1
• The AUGUSTUS trial demonstrated that in patients with atrial fibrillation who had acute coronary syndrome or PCI, apixaban without aspirin resulted in less bleeding without significant differences in ischemic events compared to regimens that included both 3

Monitoring Recommendations

• Monitor for signs of bleeding (unexpected bruising, nosebleeds, blood in urine/stool) 2
• Watch for symptoms of thromboembolism (pain, swelling, shortness of breath) 1
• Check hemoglobin levels weekly until stable, then regularly during treatment 1
• Discontinue epoetin if hemoglobin rises above 12 g/dL or increases by more than 1 g/dL in any 2-week period 1

In conclusion, while epoetin can be used with apixaban and aspirin, the combination significantly increases both bleeding and thrombotic risks. The decision to use epoetin should be made only after careful consideration of these risks, and alternative treatments for anemia should be explored first.