title: Point-of-care genetic profiling and/or platelet function testing in acute coronary syndrome.
abstract: 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.
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Collet
authors.forename: Mathieu
authors.initials: M
authors.lastname: Kerneis
authors.forename: Jean-Sébastien
authors.initials: JS
authors.lastname: Hulot
authors.forename: Stephen A
authors.initials: SA
authors.lastname: O'Connor
authors.forename: Johanne
authors.initials: J
authors.lastname: Silvain
authors.forename: Nicolas
authors.initials: N
authors.lastname: Mansencal
authors.forename: Delphine
authors.initials: D
authors.lastname: Brugier
authors.forename: Jérémie
authors.initials: J
authors.lastname: Abtan
authors.forename: Olivier
authors.initials: O
authors.lastname: Barthélémy
authors.forename: Jean-Baptiste
authors.initials: JB
authors.lastname: Vignalou
authors.forename: Laurent
authors.initials: L
authors.lastname: Payot
authors.forename: Hélène
authors.initials: H
authors.lastname: Rousseau
authors.forename: Eric
authors.initials: E
authors.lastname: Vicaut
authors.affiliation: Gilles Montalescot, MD, PhD, Institut de Cardiologie, Bureau 2-236, Pitié-Salpêtrière Hospital, 47 Boulevard de l'Hôpital, 75013 Paris, France, Tel.:+33 1 4216 3006, Fax:+33 1 4216 2931, E-mail: gilles.montalescot@psl.aphp.fr.
authors.forename: Gilles
authors.initials: G
authors.lastname: Montalescot
mesh_terms: D054058:Acute Coronary Syndrome / Q000097:blood* / Q000188:drug therapy / Q000235:genetics; D000368:Aged; D000483:Alleles; D001792:Blood Platelets / Q000166:cytology; D000077144:Clopidogrel; D065731:Cytochrome P-450 CYP2C19 / Q000235:genetics; D005260:Female; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D062645:Percutaneous Coronary Intervention; D010641:Phenotype; D015539:Platelet Activation; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use; D010979:Platelet Function Tests / Q000379:methods*; D000067716:Point-of-Care Testing; D000068799:Prasugrel Hydrochloride / Q000008:administration & dosage; D011446:Prospective Studies; D058925:Receptors, Purinergic P2Y12 / Q000235:genetics; D015203:Reproducibility of Results; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives
chemical_list: C548576:P2RY12 protein, human; D010975:Platelet Aggregation Inhibitors; D058925:Receptors, Purinergic P2Y12; D000077144:Clopidogrel; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D000068799:Prasugrel Hydrochloride; D013988:Ticlopidine
keywords: Platelet pharmacology; antiplatelet drugs; atherothrombosis; clinical trials; pharmacodynamics