Controversies and future perspectives of antiplatelet therapy in secondary stroke prevention

Area of Science:

• Cardiology
• Neurology
• Pharmacology

Background:

• Antiplatelet agents are crucial for acute arterial thrombotic events and thrombus prevention.
• Current agents like aspirin and clopidogrel provide only a modest risk reduction (approx. 25%) for vascular events.
• There is a significant unmet need for more effective antiplatelet therapies with a lower risk of bleeding.

Purpose of the Study:

• To review novel antiplatelet agents under investigation for secondary stroke prevention.
• To discuss unique considerations in stroke prevention, including disease heterogeneity and increased bleeding risk post-stroke.
• To examine the evidence for combination antiplatelet therapy and the phenomenon of antiplatelet resistance.

Main Methods:

• Literature review of new antiplatelet agents.
• Analysis of randomized trials on combination therapy and antiplatelet resistance.
• Discussion of specific agents: P2Y12 antagonists, cilostazol, sarpogrelate, terutroban, and SCH 530348.

Main Results:

• Several new antiplatelet agents are in development for secondary stroke prevention.
• Combination therapy (aspirin and clopidogrel) may offer benefits in the acute phase, but evidence is from small trials.
• No definitive trial evidence links aspirin resistance or concomitant use of clopidogrel with proton pump inhibitors to recurrent ischemic events.

Conclusions:

• More effective antiplatelet therapies are required for secondary stroke prevention.
• The heterogeneity of ischemic stroke and altered blood-brain barrier post-stroke necessitate careful treatment strategies.
• While combination therapy shows promise, routine use of clopidogrel with proton pump inhibitors is not recommended due to lack of proven benefit and potential risks.