title: Genotype- and Phenotype-Directed Personalization of Antiplatelet Treatment in Patients with Non-ST Elevation Acute Coronary Syndromes Undergoing Coronary Stenting.
abstract: OBJECTIVE
  We evaluated the effectiveness of genotype- and phenotype-directed individualization of P2Y12 inhibitors to decrease high on-treatment platelet reactivity (HOPR).
  
  
  METHODS
  Sixty-five patients undergoing percutaneous coronary intervention for non-ST elevation acute coronary syndromes were randomly assigned to genotype- or phenotype-directed treatment. All patients were screened for CYP2C19(*)2, (*)3, or (*)17 alleles by using the Verigene CLO assay (Nanosphere, Northbrook, IL, USA). The P2Y12 reaction unit (PRU) was measured using the VerifyNow P2Y12 assay (Accumetrics, San Diego, CA, USA). 21 CYP2C19 (*)2 or (*)3 carriers (65.6%) and 11 patients with HOPR (33.3%), defined as a PRU value ≥230, were given 90 mg ticagrelor twice daily; non-carriers and patients without HOPR were given 75 mg clopidogrel daily. The primary endpoint was the percentage of patients with HOPR after 30 days of treatment.
  
  
  RESULTS
  PRU decreased following both genotype- and phenotype-directed therapies (242±83 vs. 109±90, p<0.001 in the genotype-directed group; 216±74 vs. 109±90, p=0.001 in the phenotype-directed group). Five subjects (16.2%) in the genotype-directed group and one (3.3%) in the phenotype-directed group had HOPR at day 30 (p=0.086). All patients with HOPR at the baseline who received ticagrelor had a PRU value of <230 after 30 days of treatment. Conversely, clopidogrel did not lower the number of patients with HOPR at the baseline.
  
  
  CONCLUSIONS
  Tailored antiplatelet therapy according to point-of-care genetic and phenotypic testing may be effective in decreasing HOPR after 30 days.
authors.affiliation: Division of Cardiology, Yonsei University Wonju College of Medicine, Wonju, Korea.
authors.forename: Sung Gyun
authors.initials: SG
authors.lastname: Ahn
authors.forename: Junghan
authors.initials: J
authors.lastname: Yoon
authors.forename: Juwon
authors.initials: J
authors.lastname: Kim
authors.forename: Young
authors.initials: Y
authors.lastname: Uh
authors.forename: Kyung Min
authors.initials: KM
authors.lastname: Kim
authors.forename: Ji Hyun
authors.initials: JH
authors.lastname: Lee
authors.forename: Jun-Won
authors.initials: JW
authors.lastname: Lee
authors.forename: Young Jin
authors.initials: YJ
authors.lastname: Youn
authors.forename: Min-Soo
authors.initials: MS
authors.lastname: Ahn
authors.forename: Jang-Young
authors.initials: JY
authors.lastname: Kim
authors.forename: Byung-Su
authors.initials: BS
authors.lastname: Yoo
authors.forename: Seung-Hwan
authors.initials: SH
authors.lastname: Lee
authors.forename: Seung-Jea
authors.initials: SJ
authors.lastname: Tahk
authors.forename: Kyung-Hoon
authors.initials: KH
authors.lastname: Choe
keywords: Antiplatelet agents; Genetic testing; Platelet function tests; Point-of-care systems
references.citation: N Engl J Med. 2001 Aug 16;345(7):494-502
references.pmid: 11519503
references.citation: J Am Coll Cardiol. 2011 Jan 18;57(3):280-9
references.pmid: 21232664
references.citation: Circulation. 2011 Dec 6;124(23):2574-609
references.pmid: 22064598
references.citation: N Engl J Med. 2009 Sep 10;361(11):1045-57
references.pmid: 19717846
references.citation: JAMA. 2011 Nov 23;306(20):2221-8
references.pmid: 22088980
references.citation: J Am Coll Cardiol. 2010 Sep 14;56(12):919-33
references.pmid: 20828644
references.citation: Circulation. 2009 Jan 20;119(2):237-42
references.pmid: 19118249
references.citation: Circulation. 2006 Aug 22;114(8):774-82
references.pmid: 16908769
references.citation: Circulation. 2009 Jun 30;119(25):3207-14
references.pmid: 19528339
references.citation: N Engl J Med. 2007 Nov 15;357(20):2001-15
references.pmid: 17982182
references.citation: Platelets. 2011;22(4):305-7
references.pmid: 21480769
references.citation: Circulation. 2009 May 19;119(19):2625-32
references.pmid: 19451364
references.citation: J Am Coll Cardiol. 2008 Sep 30;52(14):1128-33
references.pmid: 18804738
references.citation: JAMA. 2011 Mar 16;305(11):1097-105
references.pmid: 21406646
references.citation: J Clin Microbiol. 2010 Nov;48(11):3997-4002
references.pmid: 20826644
references.citation: Lancet. 2010 Oct 9;376(9748):1233-43
references.pmid: 20817281
references.citation: Lancet. 2012 May 5;379(9827):1705-11
references.pmid: 22464343
references.citation: N Engl J Med. 2012 Nov 29;367(22):2100-9
references.pmid: 23121439
references.citation: Am Heart J. 2007 Jan;153(1):29-35
references.pmid: 17174633
references.citation: J Am Coll Cardiol. 2012 Jun 12;59(24):2159-64
references.pmid: 22520250
references.citation: Am J Clin Pathol. 2011 Oct;136(4):604-8
references.pmid: 21917683
references.citation: Am Heart J. 2011 Feb;161(2):383-90
references.pmid: 21315223
references.citation: J Am Coll Cardiol. 2011 Jun 21;57(25):2474-83
references.pmid: 21679849
references.citation: Korean Circ J. 2009 Dec;39(12):512-8
references.pmid: 20049136
references.citation: Cardiovasc Ther. 2012 Feb;30(1):5-11
references.pmid: 21129165
references.citation: Circulation. 2011 Jun 14;123(23):2736-47
references.pmid: 21670242
references.citation: Genet Test Mol Biomarkers. 2012 Jun;16(6):500-3
references.pmid: 22239289
references.citation: JAMA. 2009 Aug 26;302(8):849-57
references.pmid: 19706858
references.citation: JACC Cardiovasc Interv. 2012 Mar;5(3):259-67
references.pmid: 22440490