What is the recommended reversal agent for Brilinta (ticagrelor)?

Reversal Agent for Brilinta (Ticagrelor)

There is currently no FDA-approved reversal agent for ticagrelor in routine clinical practice, and platelet transfusions are ineffective for reversing its antiplatelet effects. 1

Current Standard Management

Why Platelet Transfusion Does Not Work

• Platelet transfusions do not reverse ticagrelor's antiplatelet effects because ticagrelor is a reversible P2Y12 inhibitor that remains in the plasma and immediately inhibits transfused platelets 2, 1, 3
• Studies demonstrate that even mixing up to 90% control platelets with ticagrelor-treated blood cannot fully restore platelet aggregation 3
• The residual drug in plasma continues to inhibit donor platelets for at least 10 hours after the last ticagrelor dose 3
• This is fundamentally different from aspirin or irreversible P2Y12 inhibitors (clopidogrel, prasugrel), where platelet transfusion can be effective 2

Supportive Hemostatic Measures

For patients with active bleeding on ticagrelor, the following supportive measures should be used 2:

• Antifibrinolytics (tranexamic acid or aminocaproic acid) may support hemostasis, though they do not reverse the platelet inhibitory effects 2
• Desmopressin (DDAVP) may be considered to support hemostasis, though evidence is limited and it does not reverse antiplatelet effects 2
• Local hemostatic measures should be maximized first (nasal packing for epistaxis, surgical hemostasis, etc.) 2

Bridging Therapy for High-Risk Situations

When Ticagrelor Must Be Stopped But Thrombotic Risk Is Very High

In patients at extremely high risk of stent thrombosis (particularly within 2 weeks of PCI, proximal LAD stent, ACS presentation, long stents, or cancer), consider bridging therapy 2, 4:

• Cangrelor (preferred): IV reversible P2Y12 inhibitor with quick offset of action, given as continuous infusion 2, 4
• Tirofiban or eptifibatide: IV reversible GP IIb/IIIa inhibitors may be considered as alternatives 2, 4
• Do NOT use low-molecular-weight heparin as bridging therapy—it does not reduce stent thrombosis risk and increases bleeding 2, 4

Investigational Reversal Agent: Bentracimab (PB2452)

Mechanism and Evidence

• Bentracimab is a monoclonal antibody fragment that binds ticagrelor and its active metabolite with high affinity, providing immediate and sustained reversal 5, 6, 7
• In a Phase 2 trial of 150 patients requiring urgent surgery or with major hemorrhage, bentracimab provided rapid reversal within 5-10 minutes, sustained for >24 hours 7
• Adjudicated hemostasis was achieved in >90% of patients (P<0.001) 7
• Approximately 5% of patients had thrombotic events; no allergic or infusion-related reactions occurred 7

Current Status

• Bentracimab is NOT yet FDA-approved but Phase 3 trials are ongoing 2, 6, 7
• This represents the most promising future option for ticagrelor reversal in life-threatening bleeding or urgent surgery 2, 5, 6

Timing of Ticagrelor Discontinuation Before Surgery

When urgent reversal is not available, timing of discontinuation is critical 4:

• Minimum 3 days before elective surgery (European Society of Cardiology recommendation) 4
• Preferred 5 days before surgery with significant bleeding risk (American College of Cardiology/American Heart Association recommendation) 4
• For CABG, withhold for 3-5 days preferred to minimize bleeding risk 4

Critical Pitfalls to Avoid

• Never rely on platelet transfusion to reverse ticagrelor—it will not work and wastes resources 2, 1, 3
• Do not use LMWH as "bridging" when stopping ticagrelor in high stent thrombosis risk patients—it does not prevent thrombosis 2, 4
• Ticagrelor is not dialyzable, so hemodialysis cannot remove the drug 1
• Monitor ECG in overdose situations, as ventricular pauses can occur 1

Practical Algorithm for Active Bleeding on Ticagrelor

1. Immediately discontinue ticagrelor (and hold next dose) 4
2. Maximize local hemostatic measures (direct pressure, packing, cautery, surgical control) 2
3. Administer antifibrinolytics (tranexamic acid 1g IV or aminocaproic acid) 2
4. Consider desmopressin (0.3 mcg/kg IV over 30 minutes) 2
5. Do NOT transfuse platelets unless patient is going to immediate surgery (and even then, benefit is uncertain) 2, 1, 3
6. Assess stent thrombosis risk: If very high (recent PCI <2 weeks, high-risk anatomy), consider bridging with cangrelor or GP IIb/IIIa inhibitor 2, 4
7. Supportive care: Transfuse RBCs for anemia, correct coagulopathy if present, hemodynamic support 2