Point-of-care genetic profiling and/or platelet function testing in acute coronary syndrome

Thromb Haemost. 2016 Jan;115(2):382-91. doi: 10.1160/TH15-05-0394. Epub 2015 Oct 1.


Our aim was to demonstrate that the sequential use of the Verigene® rapid CYP2C19 test for genetic profiling and the VerifyNowTM bedside test for platelet function measurement in ACS patients may optimise P2Y12 inhibition. "Rapid" (CYP2C19*1/*1 or CYP2C19*17 carriers, n=211) and "slow" metabolisers (CYP2C19*2 carriers, n=58) were first put on clopidogrel and prasugrel for ≥ 2 weeks, respectively. Patients with low platelet reactivity (PRU<30) on prasugrel or high platelet reactivity (>208 PRU) on clopidogrel were then switched to clopidogrel and prasugrel, respectively. Our objectives were (i) to demonstrate that the proportion of "rapid" metabolisers on 75 mg of clopidogrel within 30-208 (PRU) of P2Y12 inhibition is non-inferior to "slow" metabolisers on prasugrel 10 mg and (ii) to evaluate the same end-point after switching drugs. The proportion of "rapid" and "slow" metabolisers within 30-208 PRU of P2Y12 inhibition was 71% and 56.9%, respectively, an absolute difference of +14.1% (95% CI, -0.05% to 28.28%) with a non-inferiority margin greater than the predefined margin of -10%. Among patients out of target, all but one "slow" metabolisers displayed low-on prasugrel platelet reactivity while the majority of "rapid" metabolisers (68%) displayed high-on clopidogrel platelet reactivity. After switching, the proportion of patients within 30-208 PRU of P2Y12 inhibition was 83.6% and 79.3% in "rapid" and "slow" metabolisers, respectively (+4.3%, 95% CI -7.3% to 15.9%). In conclusion, this study demonstrates a loose relationship between genotype and platelet function phenotype approaches but that they are complementary to select prasugrel or clopidogrel MD in stented ACS patients.

Keywords: Platelet pharmacology; antiplatelet drugs; atherothrombosis; clinical trials; pharmacodynamics.

Publication types

  • Multicenter Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Coronary Syndrome / blood*
  • Acute Coronary Syndrome / drug therapy
  • Acute Coronary Syndrome / genetics
  • Aged
  • Alleles
  • Blood Platelets / cytology
  • Clopidogrel
  • Cytochrome P-450 CYP2C19 / genetics
  • Female
  • Genetic Testing
  • Genotype
  • Humans
  • Male
  • Middle Aged
  • Percutaneous Coronary Intervention
  • Phenotype
  • Platelet Activation
  • Platelet Aggregation Inhibitors / administration & dosage
  • Platelet Aggregation Inhibitors / chemistry
  • Platelet Aggregation Inhibitors / therapeutic use
  • Platelet Function Tests / methods*
  • Point-of-Care Testing*
  • Prasugrel Hydrochloride / administration & dosage
  • Prospective Studies
  • Receptors, Purinergic P2Y12 / genetics
  • Reproducibility of Results
  • Ticlopidine / administration & dosage
  • Ticlopidine / analogs & derivatives


  • P2RY12 protein, human
  • Platelet Aggregation Inhibitors
  • Receptors, Purinergic P2Y12
  • Clopidogrel
  • CYP2C19 protein, human
  • Cytochrome P-450 CYP2C19
  • Prasugrel Hydrochloride
  • Ticlopidine