Platelet Reactivity and Risk of Ischemic Stroke After Coronary Drug-Eluting Stent Implantation: From the ADAPT-DES Study

JACC Cardiovasc Interv. 2018 Jul 9;11(13):1277-1286. doi: 10.1016/j.jcin.2018.01.263. Epub 2018 Jun 13.

Abstract

Objectives: The authors sought to investigate the association between P2Y12 reaction units (PRU) and the risk of ischemic stroke (IS) after successful coronary drug-eluting stents (DES) implantation.

Background: The association between platelet reactivity on clopidogrel and the risk for ischemic cerebrovascular events remains unclear.

Methods: Incidence, predictors, and prognostic impact of IS were evaluated among patients enrolled in the multicenter, prospective ADAPT-DES (Assessment of Dual AntiPlatelet Therapy With Drug Eluting Stents) study. By protocol, patients were maintained on aspirin for 2 years and clopidogrel for at least 1 year. Baseline platelet reactivity on clopidogrel and aspirin were assessed by means of VerifyNow point-of-care assay after successful DES implantation.

Results: Among 8,582 patients enrolled, 68 (0.8%) had an IS during 2-year follow-up. Across the spectrum of PRU, rates of IS were progressively greater as patients transitioned from the lowest quintile of PRU (more P2Y12 receptor inhibition; 2-year rate of 0.51%) to the highest quintile of PRU (less P2Y12 receptor inhibition; 2-year rate of 1.34%; adjusted p = 0.04). PRU >208 was independently associated with higher risk of IS at 2 years (adjusted hazard ratio 1.81; 95% confidence interval 1.08 to 3.04; p = 0.03). The association between higher PRU and risk for IS was also consistent in patients with versus without high CHA2DS2-VASc score (pinteraction = 0.30) and in those on or off oral anticoagulation at discharge (pinteraction = 0.99). Occurrence of IS was strongly associated with increased risk of all-cause mortality at 2 years (adjusted HR: 4.16; 95% CI: 1.95 to 8.87; p < 0.0001).

Conclusions: Higher PRU was associated with increased risk of IS after coronary DES implantation. Ensuring adequate platelet P2Y12 receptor inhibition may reduce the risk of IS in this patient population. (Assessment of Dual AntiPlatelet Therapy With Drug Eluting Stents [ADAPT-DES]; NCT00638794).

Keywords: drug-eluting stent(s); percutaneous coronary intervention; platelet reactivity; stroke.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aspirin / administration & dosage
  • Biomarkers / blood
  • Blood Platelets / drug effects
  • Blood Platelets / metabolism*
  • Brain Ischemia / blood
  • Brain Ischemia / etiology*
  • Brain Ischemia / mortality
  • Brain Ischemia / prevention & control
  • Clopidogrel / administration & dosage
  • Coronary Artery Disease / blood
  • Coronary Artery Disease / mortality
  • Coronary Artery Disease / therapy*
  • Drug Therapy, Combination
  • Drug-Eluting Stents*
  • Female
  • Germany
  • Humans
  • Male
  • Middle Aged
  • Percutaneous Coronary Intervention / adverse effects*
  • Percutaneous Coronary Intervention / instrumentation*
  • Percutaneous Coronary Intervention / mortality
  • Platelet Activation*
  • Platelet Aggregation Inhibitors / administration & dosage
  • Platelet Function Tests
  • Prospective Studies
  • Purinergic P2Y Receptor Antagonists / administration & dosage
  • Receptors, Purinergic P2Y12 / blood*
  • Receptors, Purinergic P2Y12 / drug effects
  • Registries
  • Risk Assessment
  • Risk Factors
  • Stroke / blood
  • Stroke / etiology*
  • Stroke / mortality
  • Stroke / prevention & control
  • Time Factors
  • Treatment Outcome
  • United States

Substances

  • Biomarkers
  • P2RY12 protein, human
  • Platelet Aggregation Inhibitors
  • Purinergic P2Y Receptor Antagonists
  • Receptors, Purinergic P2Y12
  • Clopidogrel
  • Aspirin

Associated data

  • ClinicalTrials.gov/NCT00638794