Ticagrelor yields consistent dose-dependent inhibition of ADP-induced platelet aggregation in patients with atherosclerotic disease regardless of genotypic variations in P2RY12, P2RY1, and ITGB3

References

• Bertrand M, Simoons M, Fox K, Wallentin L, Hamm C, McFadden E, De Feyter P, Specchia G, Ruzyllo W. Management of acute coronary syndromes in patients presenting without persistent ST-segment elevation. The Task Force on the Management of Acute Coronary Syndromes of the European Society of Cardiology. Eur Heart J 2002; 23: 1809–1840
   PubMed Web of Science ®Google Scholar
• Storey RF. Biology and pharmacology of the platelet P2Y12 receptor. Curr Pharm Des 2006; 12: 1255–1259
   PubMed Web of Science ®Google Scholar
• Antiplatelet Trialists' Collaboration. Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients. Brit Med J 2002;324:71–86
   Google Scholar
• Savi P, Nurden P, Nurden A, Levy-Toledano S, Herbert JM. Clopidogrel: A review of its mechanism of action. Platelets 1998; 9: 251–255
   PubMed Web of Science ®Google Scholar
• The Clopidogrel in Unstable Angina to Prevent Recurrent Events Trial Investigators. Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation. N Engl J Med 2001;345:494–502
   Google Scholar
• Gurbel PA, Bliden KP, Hiatt BL, O'Connor CM. Clopidogrel for coronary stenting: Response variability, drug resistance, and the effect of pretreatment platelet reactivity. Circulation 2003; 107: 2908–2913
   PubMed Web of Science ®Google Scholar
• Matetzky S, Shenkman B, Guetta V, Shechter M, Bienart R, Goldenberg I, Novikov I, Pres H, Savion N, Varon D, Hod H. Clopidogrel resistance is associated with increased risk of recurrent atherothrombotic events in patients with acute myocardial infarction. Circulation 2004; 109: 3171–3175
   PubMed Web of Science ®Google Scholar
• Barragan P, Bouvier J-L, Roquebert P-O, Macaluso G, Commeau P, Comet B, Lafont A, Camoin L, Walter U, Eigenthaler M. Resistance to thienopyridines: Clinical detection of coronary stent thrombosis by monitoring of vasodilator-stimulated phosphoprotein phosphorylation. Cath Cardiovasc Interv 2003; 59: 295–302
   PubMed Web of Science ®Google Scholar
• Gurbel PA, Bliden KP, Samara W, Yoho JA, Hayes K, Fissha MZ, Tantry US. Clopidogrel effect on platelet reactivity in patients with stent thrombosis: Results of the CREST study. J Am Coll Cardiol 2005; 46: 1827–1832
   PubMed Web of Science ®Google Scholar
• Frere C, Cuisset T, Quilici J, Camoin L, Carvajal J, Morange P, Lambert M, Juhan-Vague I, Bonnet J, Alessi M. ADP-induced platelet aggregation and platelet reactivity index VASP are good predictive markers for clinical outcomes in non-ST elevation acute coronary syndrome. Thromb Haemost 2007; 98: 838–843
   PubMed Web of Science ®Google Scholar
• Fontana P, Dupont A, Gandrille S, Bachelot-Loza C, Reny J-L, Aiach M, Gaussem P. Adenosine diphosphate-induced platelet aggregation is associated with P2Y12 gene sequence variations in healthy subjects. Circulation 2003; 108: 989–995
   PubMed Web of Science ®Google Scholar
• Hetherington SL, Singh RK, Lodwick D, Thompson JR, Goodall AH, Samani NJ. Dimorphism in the P2Y1 ADP receptor gene is associated with increased platelet activation response to ADP. Arterioscler Thromb Vasc Biol 2005; 25: 252–257
   PubMed Web of Science ®Google Scholar
• Angiolillo DJ, Fernandez-Ortiz A, Bernardo E, Ramirez C, Cavallari U, Trabetti E, Sabate M, Jimenez-Quevedo P, Hernandez R, Moreno R. Lack of association between the P2Y12 receptor gene polymorphism and platelet response to clopidogrel in patients with coronary artery disease. Thromb Res 2005; 116: 491–497
   PubMed Web of Science ®Google Scholar
• Von Beckerath N, Von Beckerath O, Koch W, Eichinger M, Schomig A, Kastrati A. P2Y12 gene H2 haplotype is not associated with increased adenosine diphosphate-induced platelet aggregation after initiation of clopidogrel therapy with a high loading dose. Blood Coagul Fibrinol 2005; 16: 199–204
   PubMed Web of Science ®Google Scholar
• Smith SMG, Judge HM, Peters G, Armstrong M, Fontana P, Gaussem P, Daly ME, Storey RF. Common sequence variations in the P2Y12 and CYP3A5 genes do not explain the variability in the inhibitory effects of clopidogrel therapy. Platelets 2006; 17: 250–258
   PubMed Web of Science ®Google Scholar
• Fontana P, Remones V, Reny J-L, Aiach M, Gaussem P. P2Y1 gene polymorphism and ADP-induced platelet response. J Thromb Haemost 2005; 3: 2349–2350
   PubMed Web of Science ®Google Scholar
• Goodman T, Ferro A, Sharma P. Pharmacogenetics of aspirin resistance: A comprehensive systematic review. Br J Clin Pharmacol 2008; 66: 222–232
   PubMed Web of Science ®Google Scholar
• Angiolillo DJ, Fernandez-Ortiz A, Bernardo E, Alfonso F, Sabaté M, Fernández C, Stranieri C, Trabetti E, Pignatti PF, Macaya C. PlA polymorphism and platelet reactivity following clopidogrel loading dose in patients undergoing coronary stent implantation. Blood Coagul Fibrinol 2004; 15: 89–93
   PubMed Web of Science ®Google Scholar
• Benze G, Heinrich J, Schulte H, Rust S, Nowak-Gottl U, Tataru MC, Kohler E, Assmann G, Junker R. Association of the GPIa C807T and GPIIIa PlA1/A2 polymorphisms with premature myocardial infarction in men. Eur Heart J 2002; 23: 325–330
   PubMedGoogle Scholar
• Cooke GE, Liu-Stratton Y, Ferketich AK, Moeschberger ML, Frid DJ, Magorien RD, Bray PF, Binkley PF, Goldschmidt-Clermont PJ. Effect of platelet antigen polymorphism on platelet inhibition by aspirin, clopidogrel, or their combination. J Am Coll Cardiol 2006; 47: 541–546
   PubMed Web of Science ®Google Scholar
• van Giezen JJJ, Humphries RG. Preclinical and clinical studies with selective reversible direct P2Y12 antagonists. Sem Thromb Haemost 2005; 31: 195–204
   PubMed Web of Science ®Google Scholar
• van Giezen JJ, Nilsson LB. AZD6140 binds to the rh-P2Y12 receptor expressed on CHO-K1 cells receptor at a site distinct from the ADP binding site but antagonizes ADP induced signaling. Paper presented at: 9th Annual Conference on Arteriosclerosis, Thrombosis and Vascular Biology; Apr 16–18, 2008; Atlanta, GA
   Google Scholar
• Husted S, Emanuelsson H, Heptinstall S, Sandset PM, Wickens M, Peters G. Pharmacodynamics, pharmacokinetics, and safety of the oral reversible P2Y12 antagonist AZD6140 with aspirin in patients with atherosclerosis: A double-blind comparison to clopidogrel with aspirin. Eur Heart J 2006; 27: 1038–1047
   PubMed Web of Science ®Google Scholar
• Cannon CP, Husted S, Harrington RA, Scirica BM, Emanuelsson H, Peters G, Storey RF. Safety, tolerability, and initial efficacy of AZD6140, the first reversible oral adenosine diphosphate receptor antagonist, compared with clopidogrel, in patients with non-ST-segment elevation acute coronary syndrome: Primary results of the DISPERSE-2 trial. J Am Coll Cardiol 2007; 50: 1844–1851
   PubMed Web of Science ®Google Scholar
• Storey RF, Husted S, Harrington RA, Heptinstall S, Wilcox RG, Peters G, Wickens M, Emanuelsson H, Gurbel P, Grande P, et al. Inhibition of platelet aggregation by AZD6140, a reversible oral P2Y12 receptor antagonist, compared with clopidogrel in patients with acute coronary syndromes. J Am Coll Cardiol 2007; 50: 1852–1856
   PubMed Web of Science ®Google Scholar
• Hulot J-S, Bura A, Villard E, Azizi M, Remones V, Goyenvalle C, Aiach M, Lechat P, Gaussem P. Cytochrome P450 2C19 loss-of-function polymorphism is a major determinant of clopidogrel responsiveness in healthy subjects. Blood 2006; 108: 2244–2247
   PubMed Web of Science ®Google Scholar
• Brandt JT, Close ST, Iturria SJ, Payne CD, Farid NA, Ernest Ii CS, Lachno DR, Salazar D, Winters KJ. Common polymorphisms of CYP2C19 and CYP2C9 affect the pharmacokinetic and pharmacodynamic response to clopidogrel but not prasugrel. J Thromb Haemost 2007; 5: 2429–2436
   PubMed Web of Science ®Google Scholar
• Collet J, Hulot J, Pena A, Villard E, Esteve J, Silvain J, Payot L, Brugier D, Cayla G, Beygui F, et al. Cytochrome P450 2C19 polymorphism in young patients treated with clopidogrel after myocardial infarction: A cohort study. Lancet 2009; 373: 309–317
   PubMed Web of Science ®Google Scholar
• Mega JL, Close SL, Wiviott SD, Shen L, Hockett RD, Brandt JT, Walker JR, Antman EM, Macias W, Braunwald E, et al. Cytochrome P-450 polymorphisms and response to clopidogrel. N Engl J Med 2009; 360: 354–362
   PubMed Web of Science ®Google Scholar
• Simon T, Verstuyft C, Mary-Krause M, Quteineh L, Drouet E, Meneveau N, Steg PG, Ferrieres J, Danchin N, Becquemont L. for the French Registry of Acute ST Elevation and Non ST Elevation Myocardial Infarction Investigators. Genetic determinants of response to clopidogrel and cardiovascular events. N Engl J Med 2009; 360: 363–375
   PubMed Web of Science ®Google Scholar
• Malek L, Kisiel B, Spiewak M, Grabowski M, Filipiak K, Kostrzewa G, Huczek Z, Ploski R, Opolski G. Coexisting polymorphisms of P2Y12 and CYP2C19 genes as a risk factor for persistent platelet activation with clopidogrel. Circ J 2008; 72: 1165–1169
   PubMed Web of Science ®Google Scholar
• James S, Åkerblom A, Cannon CP, Emanuelsson H, Husted S, Katus H, Skene S, Steg PG, Storey RF, Harrington R, et al. Comparison of Ticagrelor, the first reversible oral P2Y12 receptor antagonist, with clopidogrel in patients with acute coronary syndromes: Rationale, design, and baseline characteristics of the PLATelet inhibition and patient Outcomes (PLATO) trial. Am Heart J 2009; 157: 599–605
   PubMed Web of Science ®Google Scholar