ticagrelor and Brain-Infarction

BACKGROUND Clopidogrel is commonly used in the prevention and treatment of cardiovascular events. However, despite clopidogrel treatment, some patients experience recurrent ischemic events. CASE REPORT We present the case of a 58-year-old man with polycythemia vera and concomitant thrombocytosis who suffered 6 episodes of cerebral infarctions and 1 myocardial infarction, despite treatment with clopidogrel. Following his last ischemic event, the antiplatelet therapy was intensified from initially clopidogrel monotherapy to dual antiplatelet therapy with aspirin 75 mg once daily and ticagrelor 90 mg twice daily. Since then, no cardiovascular event has been reported. CONCLUSIONS This case report illustrates that insufficient platelet inhibition with clopidogrel monotherapy in a patient with thrombocytosis may be associated with recurrent arterial thrombosis. The exact reasons for the insufficient platelet inhibition are not known, but a plausible explanation may be an accelerated platelet turnover reflected by an increased number of immature platelets in this patient.

Topics: Adenosine; Brain Infarction; Clopidogrel; Drug Therapy, Combination; Humans; Male; Middle Aged; Myocardial Infarction; Platelet Aggregation Inhibitors; Polycythemia Vera; Purinergic P2Y Receptor Antagonists; Secondary Prevention; Thrombocytosis; Ticagrelor; Ticlopidine

Ticagrelor is a direct acting and reversibly binding P2Y12 antagonist approved for the prevention of thromboembolic events. Its potential benefits in ischemic stroke have not been investigated sufficiently. Mice were subjected to 2 hours of transient middle cerebral artery occlusion (MCAO). Mice were orally treated with ticagrelor (10 or 30 mg/kg), aspirin (60 mg/kg), or vehicle at 3 and 24 hours before MCAO and 0 and 6 hours after reperfusion. The infarct volume and neurological deficits 22 hours after reperfusion were evaluated. Cerebral blood flow (CBF) within 24 hours after MCAO was monitored. We performed western blotting and in vitro analysis using oxygen-glucose deprivation (OGD) stress in human brain microvessel endothelial cells (HBMVECs) to investigate the protective effects of ticagrelor. Ticagrelor (30 mg/kg) improved neurological deficits, reduced the infarct volume, and improved CBF. It promoted the phosphorylation of endothelial nitric oxide synthase (eNOS) and extracellular signal-regulated kinase 1/2 (ERK1/2) during the early phase after reperfusion. Increased phosphorylation of eNOS and ERK1/2 were also observed in HBMVECs after OGD stress. Ticagrelor attenuate ischemia reperfusion injury possibly via phosphorylation of eNOS and ERK1/2 in endothelial cells. This suggests that ticagrelor has neuroprotective effects via mechanisms other than its antiplatelet action.

Topics: Animals; Brain Infarction; Brain Ischemia; Cerebrovascular Circulation; Disease Models, Animal; Humans; Infarction, Middle Cerebral Artery; Mice; Neuroprotective Agents; Nitric Oxide Synthase Type III; Phosphorylation; Purinergic P2Y Receptor Antagonists; Reperfusion Injury; Stroke; Ticagrelor