New opportunities to optimize antithrombotic therapy for secondary stroke prevention

Stroke symptoms can be unsettling, even when symptoms resolve, but focusing on stroke prevention can be empowering provided that effective interventions for appropriate patient populations are available. Current options include interventions for symptomatic carotid artery stenosis, anticoagulation for atrial fibrillation, high-dose statins, new oral anticoagulants, new developments in atrial fibrillation detection, and new therapeutics are in development. For antiplatelet therapy, aspirin monotherapy is effective but dual antiplatelet therapy with the combination of aspirin and clopidogrel increases hemorrhage risks over the long term that outweigh potential benefits. In the short term though, both the Clopidogrel in High-Risk Patients with Acute Nondisabling Cerebrovascular Events (CHANCE) and Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke (POINT) trials have shown a benefit of short-term dual-antiplatelet therapy, though the increased major hemorrhage risk seen in POINT could justify applying dual-antiplatelet therapy to just the first 21 days. Furthermore, since clopidogrel is a prodrug that must be metabolized to have antiplatelet activity, it is not surprising that the treatment effect in CHANCE was limited to patients who were not carriers of loss-of-function alleles for clopidogrel metabolism. Ticagrelor, an antiplatelet agent which failed to meet its primary endpoint as monotherapy compared to aspirin in the Acute Stroke or Transient Ischaemic Attack Treated with Aspirin or Ticagrelor and Patient Outcomes (SOCRATES) trial, is currently being tested as combination therapy with aspirin compared to aspirin alone in Acute Stroke or Transient Ischaemic Attack Treated With Ticagrelor and ASA for Prevention of Stroke and Death (THALES). These developments along with improvements to the infrastructure to perform rapid evaluations and to apply intensive secondary stroke prevention interventions hold continued promise for the future.