How to reverse Brilinta (ticagrelor)?

From the Guidelines

Reversal of Brilinta (ticagrelor) is not possible with a specific antidote, but its effects can be managed by discontinuing the medication at least 5 days before surgery.

Key Considerations

• The decision to discontinue ticagrelor should be made based on the patient's individual risk of bleeding and thrombosis, as well as the urgency of the surgical procedure 1.
• Ticagrelor has a relatively short plasma half-life of 12 hours, which allows for faster recovery of platelet function compared to other antiplatelet agents 1.
• The 2017 ESC DAPT Focused Update suggests that ticagrelor discontinuation should be considered at least 3 days before surgery, but a longer duration of discontinuation (5 days) may be preferred in some cases 1.
• In patients at high risk of stent thrombosis, bridging therapy with IV reversible glycoprotein inhibitors, such as tirofiban or eptifibatide, may be considered 1.

Management Strategies

• Discontinue ticagrelor at least 5 days before surgery, if possible 1.
• Consider bridging therapy with IV reversible glycoprotein inhibitors in patients at high risk of stent thrombosis 1.
• Continue aspirin therapy, if possible, to reduce the risk of thrombosis 1.
• Monitor patients closely for signs of bleeding or thrombosis after discontinuing ticagrelor and during the perioperative period 1.

From the Research

Reversal of Brilinta (Ticagrelor)

To reverse the effects of Brilinta (ticagrelor), several strategies have been investigated:

• The use of a monoclonal antibody fragment, such as PB2452, which binds to ticagrelor with high affinity, has been shown to rapidly reverse its antiplatelet effects in healthy volunteers 2.
• Another monoclonal antibody, bentracimab, has been found to provide immediate and sustained reversal of ticagrelor's antiplatelet effects in patients undergoing urgent surgery or with major hemorrhage 3.
• Transfusion of platelet concentrates has also been proposed as a potential method to reverse ticagrelor's effects, with estimates suggesting that ≥2 units of apheresis platelet concentrates may be necessary to completely restore baseline platelet aggregation in patients after ticagrelor 4.

Mechanism of Reversal

The mechanism of reversal involves binding to the ticagrelor molecule, which prevents it from inhibiting platelet aggregation:

• PB2452 and bentracimab work by binding to ticagrelor with high affinity, thereby neutralizing its antiplatelet effects 2, 3.
• Platelet transfusion may help to restore platelet function by introducing new platelets that are not affected by ticagrelor 4.

Clinical Implications

The ability to reverse ticagrelor's effects has important clinical implications:

• It may be useful in patients who require urgent surgery or have major bleeding complications while on ticagrelor therapy 2, 3.
• The development of reversal agents, such as PB2452 and bentracimab, may improve patient outcomes and reduce the risk of bleeding complications associated with ticagrelor therapy 2, 3.