title: Hyper-Response to Clopidogrel in Japanese Patients Undergoing Transcatheter Aortic Valve Implantation.
abstract: Dual antiplatelet therapy is empirically recommended following transcatheter aortic valve implantation (TAVI). The aims of the present study were to analyze the effect of clopidogrel on platelet function and to determine the relative contribution of each CYP2C19 loss-of-function genotype undergoing TAVI.Thirty-two patients undergoing TAVI and with clopidogrel treatment were studied. All patients were treated with an Edwards SapienXT valve. Platelet reactivity was measured by the VerifyNow P2Y12 point-of-care assay at 7 days and 30 days after the procedure and a cutoff value of 95 PRU was used to identify a hyper-response of platelet reactivity. The Spartan RX(TM) sample-to-result point-of-care DNA testing system was used to identify CYP2C19 loss-of-function genotypes. Hyper-response of platelet reactivity was identified in 11 (34.3%) patients, although 24 (80%) were carriers of at least one CYP2C19 reduced-function allele. The PRU values did not change significantly from 7 days to 30 days after TAVI (136.7 ± 73.4 versus 150.4 ± 83.2, P = 0.13). The incidences of life-threatening bleeding, minor bleeding, and transfusion were significantly higher among the hyper-response of platelet reactivity group (27.3% versus 0%, P = 0.03, 36.4% versus 4.8%, P = 0.04, 81.8% versus 42.9%, P = 0.04, respectively).A hyper-response to clopidogrel was observed in one-third of patients undergoing TAVI and was related to bleeding events, even though 80% of the patients were carriers of the CYP2C19 reduced-function allele.
authors.affiliation: Department of Medicine, Teikyo University School of Medicine.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Watanabe
authors.forename: Ken
authors.initials: K
authors.lastname: Kozuma
authors.forename: Shuichi
authors.initials: S
authors.lastname: Ishikawa
authors.forename: Naoyoshi
authors.initials: N
authors.lastname: Hosogoe
authors.forename: Takaaki
authors.initials: T
authors.lastname: Isshiki
mesh_terms: D000369:Aged, 80 and over; D001024:Aortic Valve Stenosis / Q000097:blood / Q000601:surgery*; D000077144:Clopidogrel; D065731:Cytochrome P-450 CYP2C19 / Q000235:genetics / Q000378:metabolism; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D006801:Humans; D007564:Japan / Q000453:epidemiology; D008297:Male; D015539:Platelet Activation / Q000187:drug effects* / Q000235:genetics; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage; D010979:Platelet Function Tests; D019095:Point-of-Care Systems; D011183:Postoperative Complications / Q000097:blood / Q000235:genetics / Q000517:prevention & control; D011379:Prognosis; D011446:Prospective Studies; D013927:Thrombosis / Q000097:blood / Q000235:genetics / Q000517:prevention & control*; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D065467:Transcatheter Aortic Valve Replacement
chemical_list: D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D065731:Cytochrome P-450 CYP2C19; D013988:Ticlopidine