Antiplatelet resistance: a review of concepts, mechanisms and implications for management in acute ischaemic stroke and transient ischaemic attack

Acute ischaemic stroke is a leading cause of death and major disability worldwide. Approximately 50% of ischaemic strokes are caused by atherothrombotic occlusion of the cerebral arteries and antiplatelets are the mainstay of secondary stroke preventative treatment. Aspirin is beneficial if given early and short-term treatment using aspirin and clopidogrel is increasingly used for patients with intracranial atherosclerotic disease, minor stroke and/or transient ischemic attack. However, up to 50% of patients continue to have recurrent stroke and major vascular events, which may be partly due to resistance to aspirin and/or clopidogrel. Although the precise mechanisms are unknown, clinical and genetic factors associated with bioavailability and binding to target receptors are implicated. This narrative review begins with the concept of aspirin and clopidogrel resistance in ischaemic stroke and transient ischaemic attack (TIA), potential mechanisms including genetic polymorphisms and an overview of platelet function measures and limitations. We conclude by highlighting practical issues in the management of patients with aspirin and/or clopidogrel resistance including the emerging interest in ticagrelor, prasugrel and cilostazol and directions for future trials in TIA and acute ischaemic stroke.