Detecting a thienopyridine effect by platelet reactivity assessment and its implications for risk stratification

J Thromb Haemost. 2014 Apr;12(4):560-3. doi: 10.1111/jth.12505.

Abstract

Background: On-treatment platelet reactivity (OTR) is a predictor of clinical outcomes in patients receiving thienopyridine therapy.

Objective: To assess whether point-of-care platelet reactivity testing can discriminate between patients who have and have not received a thienopyridine.

Patients/methods: This was an analysis of a randomized, multicenter, pharmacodynamic trial. Subjects with coronary artery disease treated with aspirin were randomly assigned to clopidogrel 75 mg daily or prasugrel 10 mg daily for 7 days. Platelet reactivity assessment with the VerifyNow P2Y12 test was performed before study drug admistration and 24 h after the final dose. Optimal cut-offs for a detectable drug effect were identified by the use of receiver operating characteristic curve analysis.

Results: A total of 54 subjects were enrolled and completed the study. The c-statistic for the identification of a thienopyridine effect was highly significant (0.93, P < 0.001), including for the clopidogrel and prasugrel groups considered separately (P < 0.001 for both). The optimal cut-off was < 213 P2Y12 reaction units (PRU), which provided a sensitivity of 80% and a specificity of 98%. This cut-off provided a sensitivity of 58% and a specificity of 100% for a clopidogrel effect, and a sensitivity of 100% and specificity of 96% for a prasugrel effect.

Conclusions: OTR of < 213 PRU is highly specific for exposure to either clopidogrel or prasugrel. This may be useful in the management of thienoypridine-treated patients who require surgery. Furthermore, this diagnostic cut-off is similar to levels of OTR that have been associated with ischemic events in thienopyridine-treated patients, supporting the contention that a lack of drug effect is the mechanistic basis for the prognostic relationship between OTR and clinical outcomes.

Keywords: clopidogrel; platelet aggregation; platelet aggregation inhibitors; platelet function tests; prasugrel; thienopyridine.

Publication types

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

MeSH terms

  • Aged
  • Aspirin / therapeutic use
  • Blood Platelets / cytology*
  • Blood Platelets / metabolism
  • Clopidogrel
  • Coronary Artery Disease / drug therapy*
  • Drug Administration Schedule
  • Female
  • Humans
  • Male
  • Middle Aged
  • Piperazines / administration & dosage*
  • Platelet Activation
  • Point-of-Care Systems
  • Prasugrel Hydrochloride
  • Pyridines / administration & dosage*
  • Pyridines / chemistry
  • ROC Curve
  • Receptors, Purinergic P2Y12 / metabolism
  • Reproducibility of Results
  • Sensitivity and Specificity
  • Thiophenes / administration & dosage*
  • Ticlopidine / administration & dosage
  • Ticlopidine / analogs & derivatives*
  • Time Factors
  • Treatment Outcome

Substances

  • P2RY12 protein, human
  • Piperazines
  • Pyridines
  • Receptors, Purinergic P2Y12
  • Thiophenes
  • thienopyridine
  • Clopidogrel
  • Prasugrel Hydrochloride
  • Ticlopidine
  • Aspirin