Clopidogrel response variability and the advent of personalized antiplatelet therapy: A bench to bedside journey

Thrombosis and Haemostasis

Volumn 106, Issue 2, 2011, Pages 265-271

  Gurbel, Paul A ^a   Tantry, Udaya S ^a  

^a SINAI CENTER FOR THROMBOSIS RESEARCH   (United States)

Author keywords

Adp receptors; Antiplatelet drugs; Atherothrombosis; Clinical trials

Indexed keywords

ACETYLSALICYLIC ACID; ADENOSINE DIPHOSPHATE; CLOPIDOGREL; PLACEBO; PRASUGREL; PURINERGIC P2Y12 RECEPTOR; TICAGRELOR;

ACUTE CORONARY SYNDROME; DRUG DOSE COMPARISON; DRUG EFFICACY; DRUG RESPONSE; HUMAN; ISCHEMIA; LOADING DRUG DOSE; MAINTENANCE THERAPY; PERCUTANEOUS CORONARY INTERVENTION; PERSONALIZED MEDICINE; PHARMACODYNAMICS; PLATELET REACTIVITY; PRIORITY JOURNAL; PROGNOSIS; PROTEIN INTERACTION; RECEIVER OPERATING CHARACTERISTIC; REVIEW; RISK ASSESSMENT; SIGNAL TRANSDUCTION; SINGLE NUCLEOTIDE POLYMORPHISM; ST SEGMENT ELEVATION MYOCARDIAL INFARCTION; THROMBOCYTE ACTIVATION; THROMBOCYTE AGGREGATION; THROMBOCYTE FUNCTION; THROMBOSIS;

ACUTE CORONARY SYNDROME; ANGIOPLASTY, BALLOON, CORONARY; CLINICAL TRIALS AS TOPIC; HUMANS; INDIVIDUALIZED MEDICINE; PLATELET AGGREGATION INHIBITORS; POLYMORPHISM, SINGLE NUCLEOTIDE; PROSPECTIVE STUDIES; RECEPTORS, PURINERGIC P2Y12; RISK FACTORS; SIGNAL TRANSDUCTION; STENTS; THROMBOSIS; TICLOPIDINE; TRANSLATIONAL MEDICAL RESEARCH;

EID: 79961049388     PISSN: 03406245     EISSN: None     Source Type: Journal    
DOI: 10.1160/TH11-03-0167     Document Type: Review

References (69)

1. Falk E. Stable versus unstable atherosclerosis: clinical aspects. Am Heart J 1999; 138: S421-425.
2. Glover C, O'Brien ER. Pathophysiological insights from studies of retrieved coronary atherectomy tissue. Semin Interv Cardiol 2000; 5: 167-173.
3. Sano T, Motomiya T, Yamazaki H, et al. Enhancement of platelet sensitivity to ADP-aggregation by isometric exercise in arteriosclerosis patients and its prevention. Thromb Haemost 1977; 37: 329-338.
4. Hirsh PD, Hillis LD, Campbell WB, et al. Release of prostaglandins and thromboxane into the coronary circulation in patients with ischemic heart disease. N Engl J Med 1981; 304: 685-691.
5. Gurbel PA, Bliden KP, Hayes KM, et al. Platelet activation in myocardial ischemic syndromes. Expert Rev Cardiovasc Ther 2004; 2: 535-545.
6. Trip MD, Cats VM, van Capelle FJ, et al. Platelet hyperreactivity and prognosis in survivors of myocardial infarction. N Engl J Med 1990; 322: 1549-1554.
7. Hirsh J. Hyperactive platelets and complications of coronary artery disease. N Engl J Med 1987; 316: 1543-1544.
8. Tantry US, Etherington A, Bliden KP, et al. Antiplatelet therapy: current strategies and future trends. Future Cardiol 2006; 2: 343-366.
9. Gawaz M, Neumann FJ, Ott I, et al. Platelet function in acute myocardial infarction treated with direct angioplasty. Circulation 1996; 93: 229-237.
10. Tantry US, Bliden KP, Gurbel PA. Resistance to antiplatelet drugs: current status and future research. Expert Opin Pharmacother 2005; 6: 2027-2045.
11. Dorsam RT, Kunapuli SP. Central role of the P2Y12 receptor in platelet activation. J Clin Invest 2004; 113: 340-345.
12. Gurbel PA, Bliden KP, Guyer K, et al. Delayed thrombin-induced platelet-fibrin clot generation by clopidogrel: a new dose-related effect demonstrated by thrombelastography in patients undergoing coronary artery stenting. Thromb Res 2007; 119: 563-570.
13. Gurbel PA, Bliden K, Antonino M, et al. Differential Effects of Clopidogrel on Platelet Activation Measured by Annexin Binding vs. Platelet Aggregation: An Explanation for Rapid Antithrombotic Properties Even in the Presence of Clopidogrel "Resistance" Circulation 2010; 122: A19956.
14. Yip HK, Chang LT, Sun CK, et al. Impact of clopidogrel on suppression of circulating levels of soluble CD40 ligand in patients with unstable angina undergoing coronary stenting. Am J Cardiol 2006; 97: 192-194.
15. Gurbel PA, Bliden KP, Tantry US. Effect of clopidogrel with and without eptifibatide on tumor necrosis factor-alpha and C-reactive protein release after elective stenting: results from the CLEAR PLATELETS 1b study. J Am Coll Cardiol 2006; 48: 2186-2191.
16. Vivekananthan DP, Bhatt DL, Chew DP, et al. Effect of clopidogrel pretreatment on periprocedural rise in C-reactive protein after percutaneous coronary intervention. Am J Cardiol 2004; 94: 358-360.
17. Cadroy Y, Bossavy JP, Thalamas C, et al. Early potent antithrombotic effect with combined aspirin and a loading dose of clopidogrel on experimental arterial thrombogenesis in humans. Circulation 2000; 101: 2823-2828.
18. Bossavy JP, Thalamas C, Sagnard L, et al. A double-blind randomized comparison of combined aspirin and ticlopidine therapy versus aspirin or ticlopidine alone on experimental arterial thrombogenesis in humans. Blood 1998; 92: 1518-1525.
19. Järemo P, Lindahl TL, Fransson SG, et al. Individual variations of platelet inhibition after loading doses of clopidogrel. J Intern Med 2002; 252: 233-238.
20. Gurbel PA, Malinin AI, Callahan KP, et al. Effect of loading with clopidogrel at the time of coronary stenting on platelet aggregation and glycoprotein IIb/IIIa expression and platelet-leukocyte aggregate formation. Am J Cardiol 2002; 90: 312-315.
21. Gurbel PA, Cummings CC, Bell CR, et al.; Plavix Reduction Of New Thrombus Occurrence (PRONTO) trial. Onset and extent of platelet inhibition by clopidogrel loading in patients undergoing elective coronary stenting: the Plavix Reduction Of New Thrombus Occurrence (PRONTO) trial. Am Heart J 2003; 145: 239-247.
22. 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.
23. Bonello L, Tantry US, Marcucci R, et al.; Working Group on High On-Treatment Platelet Reactivity. Consensus and future directions on the definition of high ontreatment platelet reactivity to adenosine diphosphate. J Am Coll Cardiol 2010; 56: 919-933.
24. Müller I, Besta F, Schulz C, et al. Prevalence of clopidogrel non-responders among patients with stable angina pectoris scheduled for elective coronary stent placement. Thromb Haemost 2003; 89: 783-787.
25. Paniccia R, Antonucci E, Maggini N, et al. Comparison of methods for monitoring residual platelet reactivity after clopidogrel by point-of-care tests on whole blood in high-risk patients. Thromb Haemost 2010; 104: 287-292.
26. Gremmel T, Steiner S, Seidinger D, et al. Comparison of methods to evaluate clopidogrel-mediated platelet inhibition after percutaneous intervention with stent implantation. Thromb Haemost 2009; 101: 333-339.
27. Barragan P, Bouvier JL, Roquebert PO, et al. Resistance to thienopyridines: clinical detection of coronary stent thrombosis by monitoring of vasodilator6stimulated phosphoprotein phosphorylation. Catheter Cardiovasc Interv 2003; 59: 295-302.
28. Matetzky S, Shenkman B, Guetta V, et al. Clopidogrel resistance is associated with increased risk of recurrent atherothrombotic events in patients with acute myocardial infarction. Circulation 2004; 109: 3171-3175.
29. Samara WM, Bliden KP, Tantry US, et al. The difference between clopidogrel responsiveness and posttreatment platelet reactivity. Thromb Res 2005; 115: 89-94.
30. Gurbel PA, Bliden KP, Guyer K, et al. Platelet reactivity in patients and recurrent events post-stenting: results of the PREPARE POSTSTENTING Study. J Am Coll Cardiol 2005; 46: 1820-1826.
31. Gurbel PA, Bliden KP, Zaman KA, et al. Clopidogrel loading with eptifibatide to arrest the reactivity of platelets: results of the Clopidogrel Loading With Eptifibatide to Arrest the Reactivity of Platelets (CLEAR PLATELETS) study. Circulation 2005; 111: 1153-1159.
32. Sibbing D, Morath T, Braun S, et al. Clopidogrel response status assessed with Multiplate point-of-care analysis and the incidence and timing of stent thrombosis over six months following coronary stenting. Thromb Haemost 2010; 103: 151-159.
33. Sofi F, Marcucci R, Gori AM, et al. Clopidogrelnon-responsiveness and risk of cardiovascular morbidity. An updated meta-analysis. Thromb Haemost 2010; 103: 841-848.
34. Gurbel PA, Bliden KP, Samara W, et al. The clopidogrel Resistance and Stent Thrombosis (CREST) study. J Am Coll Cardiol 2005; 46: 1827-1832.
35. Bliden KP, DiChiara J, Tantry US, et al. Increased risk in patients with high platelet aggregation receiving chronic clopidogrel therapy undergoing percutaneous coronary intervention: Is the current antiplatelet therapy adequate? J Am Coll Cardiol 2007; 49: 657-666.
36. Sibbing D, Schulz S, Braun S, et al. Antiplatelet effects of clopidogrel and bleeding in patients undergoing coronary stent placement. J Thromb Haemost 2010; 8: 250-256.
37. Price MJ, Berger PB, Teirstein PS, et al. GRAVITAS Investigators. Standard- vs high-dose clopidogrel based on platelet function testing after percutaneous coronary intervention: the GRAVITAS randomized trial. J Am Med Assoc 2011; 305: 1097-1105.
38. Breet NJ, Van Werkum JW, Bouman HJ, et al. Comparison of platelet function tests in predicting clinical outcome in patients undergoing coronary stent implantation. J Am Med Assoc 2010; 303: 754-762.
39. Gurbel PA, Mahla E, Tantry US. Peri-operative platelet function testing: The potential for reducing ischaemic and bleeding risks. Thromb Haemost 2011; 106: 248-252.
40. Blindt R, Stellbrink K, de Taeye A, et al. The significance of vasodilator-stimulated phosphoprotein for risk stratification of stent thrombosis. Thromb Haemost 2007; 98: 1329-1334.
41. Frere C, Cuisset T, Quilici J, et al. 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.
42. Price MJ, Endemann S, Gollapudi RR, et al. Prognostic significance of post-clopidogrel platelet reactivity assessed by a point-of-care assay on thrombotic events after drug-eluting stent implantation. Eur Heart J 2008; 29: 992-1000.
43. Gurbel PA, Antonino MJ, Bliden KP, et al. Platelet reactivity to adenosine diphosphate and long-term ischemic event occurrence following percutaneous coronary intervention: a potential antiplatelet therapeutic target. Platelets 2008; 19: 595-604.
44. Bonello L, Paganelli F, Arpin-Bornet M, et al. Vasodilator-stimulated phosphoprotein phosphorylation analysis prior to Percutaneous coronary intervention for exclusion of postprocedural major adverse cardiovascular events. J Thromb Haemost 2007; 5: 1630-1636.
45. Marcucci R, Gori AM, Paniccia R, et al. Cardiovascular death and nonfatal myocardial infarction in acute coronary syndrome patients receiving coronary stenting are predicted by residual platelet reactivity to ADP detected by a point-of-care assay: a 12-month follow-up. Circulation 2009; 119: 237-342.
46. Sibbing D, Braun S, Morath T, et al. Platelet reactivity after clopidogrel treatment assessed with point-of-care analysis and early drug-eluting stent thrombosis. J Am Coll Cardiol 2009; 53: 849-856.
47. Cuisset T, Frere C, Quilici J, et al. Predictive values of post-treatment adenosine diphosphate-induced aggregation and vasodilator-stimulated phosphoprotein index for stent thrombosis after acute coronary syndrome in clopidogrel-treated patients. Am J Cardiol 2009; 104: 1078-1082.
48. Bonello L, Camoin-Jau L, Arques S, et al. Adjusted clopidogrel loading doses according to vasodilator-stimulated phosphoprotein phosphorylation index decrease rate of major adverse cardiovascular events in patients with clopidogrel resistance: a multicenter randomized prospective study. J Am Coll Cardiol 2008; 51: 1404-1411.
49. Bonello L, Camoin-Jau L, Armero S, et al. Tailored clopidogrel loading dose according to platelet reactivity monitoring to prevent acute and subacute stent thrombosis. Am J Cardiol 2009; 103: 5-10.
50. Valgimigli M, Campo G, de Cesare N, et al., on behalf of Tailoring Treatment With Tirofiban in Patients Showing Resistance to Aspirin and/or Resistance to Clopidogrel (3T/2R) Investigators. Intensifying platelet inhibition with tirofiban in poor responders to aspirin, clopidogrel, or both agents undergoing elective coronary intervention: results from the double-blind, prospective, randomized Tailoring Treatment with Tirofiban in Patients Showing Resistance to Aspirin and/or Resistance to Clopidogrel study. Circulation 2009; 119: 3215-3222.
51. Cuisset T, Frere C, Quilici J, et al. Glycoprotein IIb/IIIa inhibitors improve outcome after coronary stenting in clopidogrel nonresponders: a prospective, randomized study. J Am Coll Cardiol Intv 2008; 1: 649-653.
52. Gurbel PA, Tantry US. An initial experiment with personalized antiplatelet therapy: the GRAVITAS trial. J Am Med Assoc 2011; 305: 1136-1137.
53. Price MJ, Murray SS, Angiolillo DJ, et al. Primary Results From Genotype Information and Functional Testing A Prospective Pharmacogenomic Analysis of Clopidogrel Therapy. Presented at American College of Cardiology Meeting 2011 at New Orleans, LA, USA.
54. TRIGGER-PCI halted: Low events stymie platelet-reactivity trial with prasugrel, clopidogrel (http://www.theheart.org/article/1200057.do). Accessed on 4-28-2011.
55. Alexopoulos D, Dimitropoulos G, Davlouros P, et al. Prasugrel Overcomes High On-Clopidogrel Platelet Reactivity Post-Stenting More Effectively Than High- Dose (150-mg) Clopidogrel The Importance of CYP2C19 2 Genotyping. JACC Cardiovasc Interv 2011; 4: 403-410.
56. Chin CT, Roe MT, Fox KA, et al. Study design and rationale of a comparison of prasugrel and clopidogrel in medically managed patients with unstable angina/ non-ST-segment elevation myocardial infarction: the TaRgeted platelet Inhibition to cLarify the Optimal strateGy to medicallY manage Acute Coronary Syndromes (TRILOGY ACS) trial. Am Heart J 2010; 160: 16-22.e1.
57. Becker RC, Gurbel PA. Platelet P2Y12 receptor antagonist pharmacokinetics and pharmacodynamics: A foundation for distinguishing mechanisms of bleeding and anticipated risk for platelet-directed therapies. Thromb Haemost 2010; 103: 535-544.
58. van Giezen JJ, Berntsson P, Zachrisson H, et al. Comparison of ticagrelor and thienopyridine P2Y(12) binding characteristics and antithrombotic and bleeding effects in rat and dog models of thrombosis/hemostasis. Thromb Res 2009; 124: 565-571.
59. Price MJ, Tantry US, Gurbel PA. The Influence of CYP2C19 Polymorphisms on the Pharmacokinetics, Pharmacodynamics, and Clinical Effectiveness of P2Y12 Inhibitors. Rev Cardiovasc Med 2011; 12: 1-12.
60. Hulot JS, Collet JP, Silvain J, et al. Cardiovascular risk in clopidogrel-treated patients according to cytochrome P450 2C19 2 loss-of-function allele or proton pump inhibitor coadministration: A systematic meta-analysis. J Am Coll Cardiol 2010; 56: 134-143.
61. Mega JL, Simon T, Collet JP, et al. Reduced-function CYP2C19 genotype and risk of adverse clinical outcomes among patients treated with clopidogrel predominantly for pci: A meta-analysis. J Am Med Assoc 2010; 304: 1821-1830.
62. Mega JL, Close SL, Wiviott SD, et al. Cytochrome p-450 polymorphisms and response to clopidogrel. N Engl J Med 2009; 360: 354-362.
63. Mega JL, Close SL, Wiviott SD, et al. Cytochrome P450 genetic polymorphisms and the response to prasugrel: relationship to pharmacokinetic, pharmacodynamic, and clinical outcomes. Circulation 2009; 119: 2553-2560.
64. Wallentin L, James S, Storey RF, et al. Effect of CYP2C19and ABCB1 single nucleotide polymorphisms on outcomes of treatment with ticagrelor versus clopidogrel for acute coronary syndromes: A genetic substudy of the plato trial. Lancet 2010; 376: 1320-1328.
65. Pare G, Mehta SR, Yusuf S, et al. Effects of CYP2C19 genotype on outcomes of clopidogrel treatment. N Engl J Med 2010; 363: 1704-1714.
66. Bhatt DL, Simonsen KL, Emison ES, et al., on behalf of the CHARISMA Executive Committee and Investigators. CHARISMA genomics. Paper presented at: Transcatheter Cardiovascular Therapeutics 2009 Meeting; September 30, 2009; San Francisco, CA, USA.
67. Sibbing D, Koch W, Gebhard D, et al. Cytochrome 2C19 17 allelic variant, platelet aggregation, bleeding events, and stent thrombosis in clopidogrel-treated patients with coronary stent placement. Circulation 2010; 121: 512-518.
68. Mega JL, Close SL, Wiviott SD, et al. Genetic variants in ABCB1 and CYP2C19 and cardiovascular outcomes after treatment with clopidogrel and prasugrel in the TRITON- TIMI 38 trial: a pharmacogenetic analysis. Lancet 2010; 376: 1312-1319.
69. Bouman HJ, Schömig E, van Werkum JW, et al. Paraoxonase-1 is a major determinant of clopidogrel efficacy. Nat Med 2011; 17: 110-116.