Aspirin and clopidogrel: Efficacy, safety, and the issue of drug resistance

Arteriosclerosis, Thrombosis, and Vascular Biology

Volumn 24, Issue 11, 2004, Pages 1980-1987

  Cattaneo, Marco ^a  

^a UNIVERSITY OF MILAN   (Italy)

Author keywords

Antiplatelet agents; Aspirin resistance; Cardiovascular diseases; Cerebrovascular diseases; Clopidogrel resistance

Indexed keywords

ABCIXIMAB; ACETYLSALICYLIC ACID; ANTITHROMBOCYTIC AGENT; CLOPIDOGREL; DIPYRIDAMOLE; DRUG METABOLITE; FIBRINOGEN RECEPTOR ANTAGONIST; IBUPROFEN; NONSTEROID ANTIINFLAMMATORY AGENT; PRODRUG; PYRIDINE DERIVATIVE; STREPTOKINASE; THROMBOXANE A2; TICLOPIDINE;

BLEEDING; BLEEDING TIME; COST EFFECTIVENESS ANALYSIS; DOSE RESPONSE; DRUG EFFICACY; DRUG METABOLISM; DRUG RESISTANCE; DRUG SAFETY; GASTROINTESTINAL HEMORRHAGE; HUMAN; NEUTROPENIA; PATIENT CARE; PRIORITY JOURNAL; REVIEW; THROMBOCYTE AGGREGATION; THROMBOCYTE FUNCTION; THROMBOTIC THROMBOCYTOPENIC PURPURA;

ASPIRIN; DRUG RESISTANCE; HUMANS; TICLOPIDINE; TREATMENT FAILURE; TREATMENT OUTCOME; VENOUS THROMBOSIS;

EID: 8344231455     PISSN: 10795642     EISSN: None     Source Type: Journal    
DOI: 10.1161/01.ATV.0000145980.39477.a9     Document Type: Review

References (91)

1. Patrono C. Aspirin as an antiplatelet drug. N Engl J Med. 1994;330:1287-1294.
2. Cattaneo M, Gachet C. ADP receptors and clinical bleeding disorders. Arterioscler Thromb Vasc Biol. 1999;19:2281-2285.
3. Weber AA, Zimmermann KC, Mayer-Kirchrath J, Schrör K. Cyclooxygenase-2 in human platelets as a possible factor in aspirin resistance. Lancet. 1999;353:900.
4. Zimmermann N, Wenk A, Kim U, Kienzle P, Weber A-A, Gams E, Schrör K, Hohlfeld T. Functional and biochemical evaluation of platelet aspirin resistance after coronary artery bypass surgery. Circulation. 2003;108:542-547.
5. Rocca B, Secchiero P, Ciabattoni G, Ranelletti FO, Catani L, Guidotti L, Melloni E, Maggiano N, Zabuli G, Patrono C. Ciclooxygenase-2 expression is induced during human megakaryopoiesis and characterizes newly formed platelets. Proc Natl Acad Sci U S A. 2002;99:7634-7639.
6. Marcus AJ. Aspirin and thromboembolism: a possible dilemma. N Engl J Med. 1977;297:1284-1285.
7. Buczko W, Mogielnicki A, Kramkowski K, Chabielska E. Aspirin and the fibrinolytic response. Thromb Res. 2003;110:331-334.
8. Cattaneo M, D'Angelo A, Canciani MT, Asti D, Vigano-D'Angelo S, Tripodi A, Mannucci PM. Effect of oral aspirin on plasma levels of vitamin K-dependent clotting factors-studies in healthy volunteers. Thromb Haemost. 1988;59:540.
9. Husain S, Andrews NP, Mulcahy D, Panza JA, Quyyumi AA. Aspirin improves endothelial dysfunction in atherosclerosis. Circulation. 1998;97:716-720.
10. Kharbanda RK, Walton B, Allen M, Klein N, Hingorani AD, MacAllister RJ, Vallance P. Prevention of inflammation-induced endothelial dysfunction. A novel vasculo-protective action of aspirin. Circulation. 2002;105:2600-2604.
11. Collaborative overview of randomised trials of antiplatelet therapy - I: Prevention of death, myocardial infarction, and stroke by prolonged antiplatelet therapy in various categories of patients. Antiplatelet Trialists' Collaboration. BMJ. 1994;308:81-106.
12. Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high-risk patients. BMJ. 2002;324:71-86.
13. Eidelman RS, Herbert PR, Weisman SM, Hennekens CH. An update on aspirin in the primary prevention of cardiovascular disease. Arch Intern Med. 2003;163:2006-2010.
14. Landolfi R, Marchioli R, Kutti J, Gisslinger H, Rognoni G, Patrono C, Barbui T, for the European Collaboration on Low-Dose Aspirin in Polycytemia Vera Investigators. Efficacy and safety of low-dose aspirin in polycytemia vera. N Engl J Med. 2004;350:114-124.
15. Randomised trial of intravenous streptokinase, oral aspirin, both, or neither among 17,187 cases of suspected acute myocardial infarction: ISIS-2. ISIS-2 (Second International Study of Infarct Survival) Collaborative Group. Lancet. 1988;2:349-360.
16. Ramanuja S, Breall JA, Kalaria VG. Approach to "Aspirin Allergy" in cardiovascular patients. Circulation. 2004;110:e1-e4.
17. Derry S, Loke YK. Risk of gastrointestinal haemorrhage with long term use of aspirin: meta-analysis. BMJ. 2000;321:1183-1187.
18. 33P]2MeS-ADP binding sites on platelets with secretion defect, normal granule stores and normal thromboxaneA2 production. Evgidence that ADP potentiates platelet secretion independently of the formation of large platelet aggregates and thromboxane A2 production. Thromb Haemost. 1997;77:986-990.
19. Leon C, Hechler B, Freund M, Eckly A, Vial C, Ohlmann P, Dierich A, LeMeur M, Cazenave JP, Gachet C. Defective platelet aggregation and increased resistance to thrombosis in purinergic P2Y(1) receptor-null mice. J Clin Invest. 1999;104:1731-1737.
20. Cattaneo M, Lecchi A, Lombardi R, Gachet C, Zighetti ML. Platelets from a patient heterozygous for the defect of P2CYC receptors for ADP have a secretion defect despite normal thromboxane A2 production and normal granule stores: further evidence that some cases of platelet 'primary secretion defect' are heterozygous for a defect of P2CYC receptors. Arterioscler Thromb Vasc Biol. 2000;20:E101-E106.
21. Cattaneo M, Lecchi A, Randi AM, McGregor JL, Mannucci PM. Identification of a new congenital defect of platelet function characterized by severe impairment of platelet responses to adenosine diphosphate. Blood. 1992;80:2787-2796.
22. Nurden P, Savi P, Heilmann E, Bihour C, Herbert JM, Maffrand JP, Nurden A. An inherited bleeding disorder linked to a defective interaction between ADP and its receptor on platelets. J Clin Invest. 1995;95:1612-1622.
23. Cattaneo M, Zighetti ML, Lombardi R, Martinez C, Lecchi A, Conley PB, Ware J, Ruggeri ZM. Molecular bases of detective signal transduction in the platelet P2Y12 receptor of a patient with congenital bleeding. Proc Natl Acad Sci U S A. 2003;100:1978-1983.
24. Cattaneo M. Inherited platelet-based bleeding disorders. J Thromb Haemost. 2003;1:1133-1135.
25. Cazenave J-P, Gachet C. Pharmacology of ticlopidine and clopidogrel. In: Gresele P, Page C, Fuster V, Vermylen J, eds. Platelets in Thrombotyc and non-Thrombotic Disorders. Cambridge: Cambridge University Press; 2002:929-939.
26. CAPRIE Steering Committee. A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). Lancet. 1996;348:1329-1339.
27. Gaspoz JM, Coxson PG, Goldman PA, Williams LW, Kuntz KM, Hunink MG, Goldman L. Cost effectiveness of aspirin, clopidogrel, or both for secondary prevention of coronary heart disease. N Engl J Med. 2002;346:1800-1806.
28. Bennett CL, Weinberg PD, Rozenberg-Ben-Dror K, Yamold PR, Kwaan HC, Green D. Thrombotic thrombocytopenic purpura associated with ticlopidine: a review of 60 cases. Ann Intern Med. 1998;128:541-544.
29. Bennett CL, Connors JM, Carwile JM, Moake JL, Bell WR, Tarantolo SR, McCarthy LJ, Sarode R, Hatfield AJ, Feldman MD, Davidson CJ, Tsai HM. Thrombotic thrombocytopenic purpura associated with clopidogrel. N Engl J Med. 2000;342:1773-1777.
30. Zakarija A, Bandarenko N, Pandey DK, Auerbach A, Raisch DW, Kim B, Kwaan HC, McKoy JM, Schmitt BP, Davidson CJ, Yarnold PR, Gorelick PB, Bennett CL. Clopidogrel-associated TTP: an update of pharmacovigilance efforts conducted by independent researchers, pharmaceutical suppliers, and the Food and Drug Administration. Stroke. 2004;35:533-537.
31. Leon MB, Baim DS, Popma JJ, Gordon PC, Cutlip DE, Ho KK, Giambartolomei A, Diver DJ, Lasorda DM, Williams DO, Pocock SJ, Kuntz RE. A clinical trial comparing three antitrhombotic-drug regimens after coronary-artery stenting. Stent Anticoagulation Restenosis Study Investigators. N Engl J Med. 1998;339:1665-1671.
32. Moussa I, Oetgen M, Rubin G, Colombo A, Wang X, Iyer S, Maida R, Collins M, Kreps E, Moses JW. Effectiveness of clopidogrel and aspirin versus ticlopidine and aspirin in preventing stent thrombosis after coronary stent implantations. Circulation. 1999;99:2364-2366.
33. Yusuf S, Zhao F, Mehta SR, Chrolavicius S, Tognoni G, Fox KK. 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.
34. Mehta SR, Yusuf S, Peters RJ, Bertrand ME, Lewis BS, Natarajan MK, Malmberg K, Rupprecht H, Zhao F, Chrolavicius S, Copland I, Fox KA; Clopidogrel in Unstable angina to prevent Recurrent Events trial (CURE) Investigators. Effects of pretreatment with clopidogrel and aspirin followed by long-term therapy in patients undergoing percutaneous coronary intervention: the PCI-CURE study. Lancet. 2001;358:527-533.
35. Steinhubl SR, Berger PB, Mann JT 3rd, Fry ET, DeLago A, Wilmer C, Topol EJ. CREDO Investigators. Clopidogrel for the Reduction of Events During Observation. Early and sustained dual oral antiplatelet therapy following percutaneous coronary intervention: a randomized controlled trial. JAMA. 2002;288:2411-2420.
36. Kastrati A, Mehilli J, Schuhlen H, Dirschinger J, Dotzer F, ten Berg JM, Neumann FJ, Bollwein H, Volmer C, Gawaz M, Berger PB, Schomig A, for the Intracoronary Stenting and Antithrombotic Regimen-Rapid Early Action for Coronary Treatment Study Investigators. A clinical trial of abciximab in elective percutaneous coronary intervention after pretreatment with clopidogrel. N Engl J Med. 2004;350:232-238.
37. Agah R, Plow EJ, Topol EJ. GPIIb-IIIa antagonists. In: Michelson, ed. Platelets. San Diego: Academic Press; 2002:769-786.
38. Bhatt DL, Topol EJ. Scientific and therapeutic advances in antiplatelet therapy. Nature Rev. 2003;2:15-28.
39. Patrono C. Aspirin resistance: definition, mechanisms and clinical read-outs. J Thromb Haemost. 2003;1:1710-1713.
40. Buchanan MR, Brister SJ. Individual variation in the effect of ASA on platelet function: implications for the use of ASA clinically. Can J Cardiol. 1995;11:221-227.
41. Marshall PW, Williams AJ, Dixon RM, Growcott JW, Warburton S, Armstrong J, Moores J. A comparison of the effects of aspirin on bleeding time measured using the Simplate™ method and closure time measured using the PFA-100™, in healthy volunteers. Br J Clin Pharmacol. 1997;44:151-155.
42. Gum PA, Kottke-Marchant K, Poggio ED, Gurm H, Welsh PA, Brooks L, Sapp SK, Topol E J. Profile and prevalence of aspirin resistance in patients with cardiovascular disease. Am J Cardiol. 2001;88:230-235.
43. Gum PA, Kottke-Marchant K, Welsh PA, White J, topol EJ. A prospective, blinded determination of the natural history of aspirin resistance among stable patients with cardiovascular disease. J Am Coll Cardiol. 2003;41:961-965.
44. Mustard JF, Perry DW, Kinlough-Rathbone RL, Packham MA. Factors responsible for ADP-induced release reaction of human platelets. Am J Physiol. 1975;228:1757-1765.
45. Cattaneo M, Gachet C, Cazenave J-P, Packham MA. Adenosine diphosphate (ADP) does not induce thromboxane A2 generation in human platelets. Blood. 2002;99:3668-3669.
46. Paul BZ, Jin J, Kunapuli SP. Molecular mechanism of thromboxane A(2)-induced platelet aggregation. Essential role for p2t(ac) and α(2a) receptors. J Biool Chem. 1999;274:29108-29114.
47. Kawasaki T, Ozeki Y, Igawa T, Kambayashi J. Increased platelet sensitivity to collagen in individuals resistant to low-dose aspirin. Stroke. 2000;31:591-595.
48. Sane DC, McKee SA, Malinin AI, Serebruany VL. Frequency of aspirin resistance in patients with congestive heart failure treated with antecedent aspirin. Am J Cardiol. 2002;90:893-895.
49. Friend M, Vucenik I, Miller M. Platelet responsiveness to aspirin in patients with hyperlipidaemia. BMJ. 2003;326:82-83.
50. Pulcinelli FM, Pignatelli P, Celestini A, Riondino S, Gazzaniga PP, Violi F. Inhibition of platelet aggregation by aspirin progressively decreases in long-term treated patients. J Am Coll Cardiol. 2004;43:979-984.
51. 1 density. Blood. 1998;92:2382-2388.
52. Joutsi-Korhonen L, Smethurst PA, Rankin A, Gray E, Ijsseldijk M, Onley CM, Watkins NA, Williamson LM, Goodall AH, de Groot PG, Farndale RW, Ouwehand WH. The low-frequency allele of the platelet collagen signaling receptor glycoprotein VI is associated with reduced functional responses and expression. Blood. 2003;101:4372-4379.
53. Mangin P, Ohlman P, Eckly A, Cazenave J-P, Lanza F, Gachet C. The P2Y(1) receptor plays an essential role in the platelet shape change incuced by collagen when TxA2 formation is prevented. J Thromb Haemost. 2004;2:969-977.
54. Kundu SK, Heilmann E, Sio R, Garcia C, Ostgaart R. Characterization of an in vitro platelet function analyzer, PFA-100™. Clin Appl Thromb Hemost. 1996;2:241-249.
55. Fressinaud E, Veyradiers A, Truchaud F, Martin I, Boyer-Neumann C, Trossaert M, Meyer D. Screening for von Willebrand disease with a new analyzer using high shear stress: a study of 60 cases. Blood. 1998;91:1325-1331.
56. Cattaneo M, Federici AB, Lecchi A, Agati B, Lombardi R, Stabile F, Bucciarelli P. Evaluation of the PFA-100 system in the diagnosis and therapeutic monitoring of patients with von Willebrand disease. Thromb Haemost. 1999;82:35-39.
57. Andersen K, Hurlen M, Arnesen H, Seljeflot I. Aspirin nonresponsiveness as measured by PFA-100 in patients with coronary artery disease. Thromb Res. 2003;108:37-42.
58. Grundmann K, Jaschonek K, Kleine B, Dichgans J, Topka H. Aspirin non-responders status in patients with recurrent cerebral ischemic attacks. J Neurol. 2003;250:63-66.
59. Roller RE, Dorr A, Ulrich S, Pilger. Effect of aspirin treatment in patients with peripheral arterial disease monitors with the platelet function analyser PFA-100. Blood Coag Fibrinol. 2002;13:277-281.
60. Christiaens L, Macchi L, Herpin D, Coisne D, Duplantier C, Allal J, Mauco G, Brizard A. Resistance to aspirin in vitro at rest and during exercise in patients with angiographically proven coronary artery disease. Thromb Res. 2003;108:115-119.
61. Chakroun T, Gerotziafas G, Robert F, Lecrubier C, Samama MM, Hatmi M, Elalamy I. In vitro aspirin resistance detected by PFA-100™ closure time: pivotal role of plasma von Willebrand factor. Br J Haematol. 2004;124:80-85.
62. A1 (GPIIIa) polymorphism but not with C807T (GPIa/IIa) and C-5T Kozak (GPIbα) polymorphisms. J Am Coll Cardiol. 2003;42:1115-1119.
63. Watala C, Golanski J, Rozalski M, Boncler MA, Luzak B, Baraniak J, Korczynski D, Drygas W. Is platelet aggregation a more important contributor than platelet adhesion to the overall platelet-related primary haemostasis measured by PFA-100? Thromb Res. 2003;109:299-306.
64. Chen W-H, Lee P-Y, Ng W, Tse H-F, Lau C-P. Aspirin resistance is associated with a high incidence of myonecrosis after non-urgent percutaneous coronary intervention despite clopidogrel pre-treatment. J Am Coll Cardiol. 2004;43:1122-1126.
65. Wang JC, Aucoin-Barry D, Manuelian D, Monbouquette R, Reisman M, Gray W, Block PC, Block EH, Ladenheim M, Simon DI. Incidence of aspirin nonresponsiveness using the ultegra rapid platelet function assay-ASA. Am J Cardiol. 2003;92:1492-1494.
66. Catella-Lawson F, Reilly MP, Kapoor SC, Cucchiara AJ, DeMarco S, Tournier B, Vyas SN, FitzGerald GA. Cyclooxygenase inhibitors and the antiplatelet effects of aspirin. N Engl J Med. 2001;345:1809-1817.
67. Cipollone F, Ciabattoni G, Patrignani P, Pasquale M, Di Gregorio D, Bucciareli T, Davi G, Cuccurullo F, Patrono C. Oxidant stress and aspirin-insensitive thromboxane biosynthesis in severe unstable angina. Circulation. 2000;102:1007-1013.
68. Halushka MK, Halushka PV. Why are some individula resistant to the cardioprotective effects of aspirin? Could it be thromboxane A2? Circulation. 2002;105:1620-1622.
69. Kearney D, Byrne A, Crean P, Cox D, Fitzgerald DJ. Optimal suppression of thromboxane A2 formation by aspirin during percutaneous transluminal coronary angioplasty: no additional effect of a selective cyclooxygenase-2 inhibitor. J Am Coll Cardiol. 2004;43:526-531.
70. Cotter G, Shemesh E, Zehavi M, Dinur I, Rudnick, Milo O, Vered Z, Krakover R, Kaluski E, Kornberg A. Lack of aspirin effect: aspirin resistance or resistance to taking aspirin? Am Heart J. 2004;147:293-300.
71. Macchi L, Christiaens L, Brabant S, Sorel N, Allal J, Mauco G, Brizard A. Resistance to aspirin in vitro is associated with increased platelet sensitivity to adenosine diphosphate. Thromb Res. 2002;107:45-49.
72. Cooke GE, Bray PF, Hamlington JD, Pham DM, Goldschmidt-Clermont PJ. P1A2 polymorphism and efficacy of aspirin. Lancet. 1998;351:1253. Letter.
73. Csiszar A, Stef G, Pacher P, Ungvari Z. Oxidative stress-induced isoprostane formation may contribute to aspirin resistance in platelets. Prostaglandins Leukot Essent Fatty Acids. 2002;66:557-558.
74. De Gaetano G, Cerletti C. Aspirin resistance: a revival of platelet aggregations tests? J Thromb Haemost. 2003;1:2048-1050.
75. Helgason CM, Bolin KM, Hoff JA, Winkler SR, Mangat A, Tortorice KL, Brace LD. Development of aspirin resistance in persons with previous ischemic stroke. Stroke. 1994;25:2331-2336.
76. Berglund U, Wallentin L. Persistent inhibition of platelet function during long-term treatment with 75 mg acetylsalicylic acid daily in men with unstable coronary artery disease. Eur Heart J. 1991;12:428-433.
77. Eikelboom JW, Hirsh J, Weitz JI, Johnston M, Yi Q, Yusuf S. Aspirin-resistant thromboxane biosynthesis and the risk of myocardial infarction, stroke, or cardiovascular death in patients at high risk for cardiovascular events. Circulation. 2002;105:1650-1655.
78. MacDonald TM, Wei L. Effect of ibuprofen on cardioprotective effect of aspirin. Lancet. 2003;361:573-574.
79. Kurth T, Glynn RJ, Walker AM, Chan KA, Buring JE, Hennekens CH, Gaziano JM. Inhibition of clinical benefits of aspirin on first myocardial infarction by nonsteroidal antiinflammatory drugs. Circulation. 2003;108:1191-1195.
80. Kimmel SE, Berlin JA, Reilly M, Jaskowiak J, Kishel L, Chittams J, Strom BL. The effects of nonselective non-aspirin non-steroidal anti-inflammatory medications on the risk of nonfatal myocardial infarction and their interaction with aspirin. J Am Coll Cardiol. 2004;43:985-990.
81. Curtis J, Wang Y, Portnay EL, Masoudi FA, Havranek EP, Krumholz HM. Aspirin, ibuprofen, and mortality after myocardial infarction: retrospective cohort study. BMJ. 2003;327:1322-1323.
82. Grotemeyer KH, Scharafinski HW, Husstedt IW. Two-year follow-up of aspirin responder and aspirin non-responder. A pilot study including 180 post-stroke patients. Thromb Res. 1993;71:397-403.
83. Mueller MR, Salat A, Stangl P, Murabito M, Pulaki S, Boehma D, Koppensteiner R, Ergun E, Mittelboeck M, Schreiner W, Losert U, Wolner E. Variable platelet response to low-dose ASA and the risk of limb deterioration in patients submitted to peripheral arterial angioplasty. Thromb Haemost. 1997;78:1003-1007.
84. Geiger J Brich J, Honig-Liedl P, Eigenthaler M, Schanzenbacher P, Herbert JM, Walter U. Specific impairment of human platelet P2Y(AC) receptor-mediated signaling by the antiplatelet drug clopidogrel. Arterioscler Thromb Vadc Biol. 1999;19:2007-2011.
85. Lau WC, Gurbel PA, Watkins PB, Neer CJ, Hopp AS, Carville DGM, Guyer KE, Tait AR, Bates ER. Contribution of hepatic cytochrome P450 3A4 metabolic activity to the phenomenon of clopidogrel resistance. Circulation. 2004;109:166-171.
86. Lau WC, Waskell LA, Watkins PB, Neer CJ, Horowitz K, Hopp AS, Tait AR, Carville GM, Guyer KE, Bates ER. Atorvastatin reduces the ability of clopidogrel to inhibit platelet aggregation: a new drug-drug interaction. Circulation. 2003;107:32-37.
87. 12 gene sequence variations in healthy subjects. Circulation. 2003;108:989-995.
88. Clarke TA, Waskell LA. The metabolism of clopidogrel is catalyzed by human cytochrome p450 3A and is inhibited by atorvastatin. Drug Metab Dispos. 2003;31:53-59.
89. Müller I, Besta F, Schulz C, Li Z, Massberg S, Gawaz M. Effects of statins on platelet inhibition by a high loading dose of clopidogrel. Circulation. 2003;108:2195-2197.
90. Mitsios JV, Papathanasiou AI, Rodis FI, Elisaf M, Goudevenos JA, Tselepis AD. Atorvastatin does not affect the antiplatelet potency of clopidogrel when it is administered concomitantly for 5 weeks in patients with acute coronary syndromes. Circulation. 2004;109-1335-1338.
91. 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.