Abstract WP116: Association Between Smoking Status, Platelet Function and Clinical Outcomes of Ticagrelor versus Clopidogrel in Patients With Minor Stroke or Transient Ischemic Attack

Abstract

Background: Association between smoking status, platelet function and clinical outcomes of ticagrelor versus clopidogrel in patients with minor stroke or transient ischemic stroke (TIA) remains unclear. Methods: A subgroup analysis was conducted of Platelet Reactivity in Acute Non-disabling Cerebrovascular Events (PRINCE) trial. PRINCE trial was a randomized, prospective, multicenter, open-label, active-controlled, and blind-endpoint trial, which randomized patients with acute minor stroke, or TIA, to ticagrelor plus aspirin or clopidogrel plus aspirin within 24 hours of symptoms onset. Patients who smoked at least one cigarette per day for at least one year in their lives were defined as smokers. Platelet reactivity was assessed by the VerifyNow P2Y12 assay at baseline, 7+2 days and 90±7 days. High-on-treatment platelet reactivity (HOPR) was defined as P2Y12 reaction units >208.Clinical outcomes included any stroke, composite clinical vascular events and bleeding events at 90 days. Results: Among 675 patients enrolled in the PRINCE trial, 370 patients (54.8%) were smokers. At 7+2 days, the proportion of HOPR in ticagrelor versus clopidogrel was significantly lower in smokers (5.2% versus 21.8%) and non-smokers (2.3% versus 34.4%). There were marginal significant interactions between treatment groups and smoking status for the proportion of HOPR ( P =0.058). There were significant interactions between treatment groups and carrier status of CYP2C19 LOF alleles for the proportion of HOPR among smokers ( P =0.04), but no significant interactions were found among non-smokers ( P =0.91). At 90±7 days, there were significant interactions between treatment groups and smoking status for the risk of new stroke (smokers, 7.0% versus 4.9%, hazard ratio [HR], 1.57 [95%CI, 0.65-3.79], P =0.39; non-smokers, 5.3% versus 13.5%, HR, 0.39 [95%CI, 0.17-0.91], P =0.01. P for interaction=0.02). Conclusions: Among patients with minor stroke or TIA, ticagrelor might be superior to clopidogrel in inhibiting platelet reactivity and reducing the risk of stroke, particularly in non-smokers. Carrier status of CYP2C19 LOF alleles might play a role in the impact of smoking status. Clinical Trial Registration : Clinicaltrials.gov NCT02506140.