Impact of smoking on platelet function of ticagrelor versus clopidogrel in minor stroke or transient ischaemic attack

Eur J Neurol. 2020 May;27(5):833-840. doi: 10.1111/ene.14171. Epub 2020 Mar 8.

Abstract

Background and purpose: It remains unclear whether smoking status has an impact on platelet reactivity and clinical outcomes of ticagrelor versus clopidogrel in patients with acute minor stroke or transient ischaemic attack (TIA).

Methods: A subgroup analysis of a randomized controlled trial was conducted. Patients with minor stroke or TIA were randomized for treatment with ticagrelor plus aspirin or clopidogrel plus aspirin. Platelet reactivity was assessed by 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. Patients who smoked one or more cigarettes per day for at least 1 year in their lives were defined as smokers.

Results: Of 675 patients enrolled in the 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% vs. 21.8%) and non-smokers (2.3% vs. 34.4%). There were marginal significant interactions between treatment groups and smoking status for the proportion of HOPR (P = 0.058). At 90 ± 7 days, there were significant interactions between treatment groups and smoking status for the risk of new stroke (smokers: 7.0% vs. 4.9%; hazard ratio, 1.57; 95% confidence interval, 0.65-3.79; P = 0.39; non-smokers: 5.3% vs. 13.5%; hazard ratio, 0.39; 95% confidence interval, 0.17-0.91; P = 0.01; P for interaction = 0.02).

Conclusions: Among patients with minor stroke or TIA, ticagrelor was superior to clopidogrel in inhibiting platelet reactivity and reducing the risk of new stroke, particularly for non-smokers.

Trial registration: ClinicalTrials.gov NCT02506140.

Keywords: clopidogrel; dual antiplatelet therapy; platelet reactivity; smoking; stroke; ticagrelor; transient ischaemic attack; transient ischaemic stroke.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Clopidogrel / therapeutic use
  • Drug Therapy, Combination
  • Humans
  • Ischemic Attack, Transient* / drug therapy
  • Platelet Aggregation Inhibitors / therapeutic use
  • Smoking
  • Stroke* / drug therapy
  • Ticagrelor / therapeutic use

Substances

  • Platelet Aggregation Inhibitors
  • Clopidogrel
  • Ticagrelor

Associated data

  • ClinicalTrials.gov/NCT02506140