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Antiplatelet Therapy Management
Antiplatelet Therapy: Managing Complex Clinical Scenarios Requiring Reversal

Released: January 23, 2025

Expiration: January 22, 2026

Jeffrey L. Saver
Jeffrey L. Saver, MD
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Key Takeaways
  • Dual antiplatelet therapy (DAPT) offers superior stroke prevention compared to single antiplatelet therapy for certain patients; however, DAPT increases the risk of hemorrhagic complications, necessitating careful risk–benefit evaluation in clinical practice.
  • Managing antiplatelet therapy in patients requiring emergent surgery or experiencing intracranial hemorrhage remains complex. Currently available reversal strategies are either nonspecific or not effective at addressing bleeding in patients on DAPT. Emerging therapies could fill this critical gap, offering specific and rapid reversal options.

Introduction
At present, there is great promise and peril with regard to antiplatelet therapy for stroke prevention. The promise is related to the drug choices currently available and evidence that dual antiplatelet therapy (DAPT) in the first few weeks after ischemic stroke is often better than single antiplatelet therapy (SAPT), not just in patients with minor stroke and transient ischemic attack (TIA), but also in patients with moderate stroke. The peril is that in the acute setting, although DAPT generally yields better outcomes than SAPT, it increases the risk of brain hemorrhage, so the challenge of treating DAPT-related hemorrhagic complications is increasing. In addition, as our population ages, the risk of intracranial hemorrhages, particularly subdural hemorrhage and intracerebral hemorrhage (ICH), is increasing, and the number of intracranial hemorrhage cases each year over the next 20 years will continue to rise. Thus, the need to better prevent and reverse hemorrhagic complications associated with antiplatelet therapy is critical.   

Overview of Currently Available Antiplatelet Agents and Mechanisms of Action
Antiplatelet therapies that are widely used as oral agents for secondary stroke prevention include aspirin, a cyclooxygenase inhibitor that has stood the test of time, and adenosine diphosphate (ADP) receptor antagonists like clopidogrel, prasugrel, and ticagrelor. Although monotherapy with ADP receptor antagonists is quite good at preventing ischemic stroke when compared to aspirin, it comes with an increased risk of bleeding complications. DAPT can provide additional benefit over monotherapy, even if used for just the first 3 to 4 weeks post stroke, for a proportion of patients with acute stroke and/or TIA. 

Another option is phosphodiesterase inhibitors: cilostazol and dipyridamole. In addition to having antiplatelet activity, they have demonstrated favorable vasodilatory and antiproliferative properties and have less bleeding risk than the other agents, making them a good option in patients who are highly prone to bleeding.   

Clinical Scenarios Requiring Antiplatelet Therapy Reversal
Some patients with a history of a stroke and on antiplatelet agents have bleeding complications or require surgery. In such cases, healthcare professionals must temporarily discontinue or reverse these agents in order for hemostasis to occur and/or for surgical procedures to be performed safely. Fortunately, the risk of being off these agents for any short period is low. 

One challenge with these scenarios is that it takes 3 to 7 days for ADP receptor antagonists to get out of a patient’s system, so if emergent surgery needs to be performed within the next 24 to 48 hours, surgeons must pursue reversal in order to achieve surgical hemostasis. In addition, patients with severe or life-threatening bleeding complications need urgent reversal strategies and cannot wait days for these medications to be eliminated passively.

Challenges With Antiplatelet Therapy Management in Emergency Situations
Current strategies for antiplatelet reversal are suboptimal. It is generally not recommended to reverse antiplatelet agents with platelet transfusions in patients with ICH, as the PATCH trial demonstrated worse outcomes in patients receiving platelet transfusions compared to those receiving standard care. However, in patients requiring surgery who have not had a brain hemorrhage, reversal with platelet transfusions may be beneficial. Platelet transfusions can be performed in patients who are on clopidogrel and prasugrel, which bind irreversibly to platelets. However, because ticagrelor binds in a reversible manner, platelet transfusions should be avoided since the active drug can bind to the new platelets introduced with the transfusion, making them ineffective.   

Desmopressin is often used in patients with intracranial hemorrhage on antiplatelet agents. Though only relatively weak, nonrandomized data support its benefits; observational data have demonstrated that it is safe to use in these patients where there are limited options for treatment. 

A Promising Future for Patients with Stroke
There is promising potential for bentracimab, a monoclonal antibody fragment that binds ticagrelor with high affinity and specificity, to become available within the next year. Bentracimab could help address the lack or reduced effectiveness of platelet transfusions associated with ticagrelor in clinical scenarios where urgent or emergent reversal is required. Another exciting development is the slow spread of mobile stroke units that can be utilized to diagnose hemorrhage in the field and allow the delivery of reversal therapies in a hyperacute time period otherwise not achievable by standard emergency department care.

Emerging therapies and mobile stroke units promise to revolutionize stroke management by addressing hemorrhagic risks and enhancing hyperacute care. These advancements align with the growing need to address the increasing prevalence of intracranial hemorrhages in an aging population.

Your Thoughts?
In what other clinical scenarios might antiplatelet reversal be challenging?  Learn more by attending a live in-person and virtual satellite symposium from the International Stroke Conference on February 6, 2025 at 6:30 AM PST or join the discussion by posting a comment below.

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How often do you encounter patients on antiplatelet therapy requiring reversal of antiplatelet agents due to bleeding complications or needing emergent surgery?

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