Is Brillinta (ticagrelor) safe to use in a patient with a history of hemorrhagic cerebrovascular accident (CVA)?

Ticagrelor (Brilinta) is Contraindicated in Patients with History of Hemorrhagic CVA

Ticagrelor is absolutely contraindicated in patients with a history of intracranial hemorrhage, including hemorrhagic cerebrovascular accident (CVA). 1 The FDA drug label explicitly lists a history of intracranial hemorrhage as a contraindication for ticagrelor use due to the high risk of recurrent intracranial bleeding in this population.

Contraindication Evidence

The FDA label for ticagrelor (Brilinta) clearly states in section 4.1:

• "Ticagrelor tablets are contraindicated in patients with a history of intracranial hemorrhage (ICH) because of a high risk of recurrent ICH in this population" 1
• "Ticagrelor tablets are contraindicated in patients with active pathological bleeding such as peptic ulcer or intracranial hemorrhage" 1

Antiplatelet Therapy Considerations in Patients with Prior Hemorrhagic CVA

Risk Assessment

Patients with prior hemorrhagic stroke are at significantly elevated risk for:

• Recurrent intracranial bleeding when on antiplatelet therapy
• Fatal outcomes if recurrent bleeding occurs 2

Alternative Antiplatelet Options

For patients with a history of hemorrhagic CVA who require antiplatelet therapy:

1. Single antiplatelet therapy with agents that have lower bleeding risk profiles may be considered if absolutely necessary
2. Avoid all P2Y12 inhibitors including ticagrelor, prasugrel, and clopidogrel if possible

Guideline Support

Multiple guidelines support this contraindication:

1. The 2012 ACCF/AHA guidelines specifically note: "Consideration should be given to the potential and as yet undetermined risk of intracranial hemorrhage in patients with prior stroke or TIA" when discussing ticagrelor 3

2. The European Society of Cardiology working group on cardiovascular pharmacotherapy specifically recommends to "Avoid ticagrelor in patients with a history of intracranial bleeding" 3

3. For prasugrel (another P2Y12 inhibitor), guidelines explicitly state: "Do not use prasugrel in patients with active pathological bleeding or a history of TIA or stroke" 3, highlighting the class-wide concern with these agents in patients with cerebrovascular events

Clinical Evidence and Case Reports

There is documented evidence of fatal outcomes with ticagrelor in patients with intracranial bleeding:

• A case report documented a lethal cerebral hemorrhage after ticagrelor intoxication, where even "iterative platelet transfusions did not improve his condition" 2

• In the SOCRATES trial studying ticagrelor in patients with ischemic stroke or TIA, patients with hemorrhagic stroke were excluded, indicating the recognized risk 4

Important Considerations for Clinicians

1. No reversal agent exists: Unlike some anticoagulants, there is no specific antidote for ticagrelor, making management of intracranial bleeding extremely challenging 2

2. Prolonged effect: Ticagrelor's antiplatelet effects persist for 5+ days after discontinuation 3

3. Risk-benefit assessment: The potential cardiovascular benefits of ticagrelor are outweighed by the substantial risk of recurrent hemorrhagic stroke in patients with prior hemorrhagic CVA

Common Pitfalls to Avoid

1. Confusing contraindications: Do not confuse recommendations for ischemic stroke/TIA (where ticagrelor may be beneficial) with hemorrhagic stroke (where it is contraindicated)

2. Underestimating bleeding risk: The risk of recurrent intracranial hemorrhage is significant and potentially fatal

3. Assuming all antiplatelet agents have similar risk profiles: Ticagrelor has more potent antiplatelet effects than aspirin and may carry higher bleeding risk

In conclusion, patients with a history of hemorrhagic CVA should not receive ticagrelor under any circumstances due to the explicit contraindication in the FDA label and the high risk of recurrent, potentially fatal intracranial bleeding.