• 1
    Antithrombotic Trialists' Collaboration. Collaborative meta–analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients. BMJ 2002;324:7186.
  • 2
    Brunton L, Lazo J, Parker K. Goodman & Gilman's The Pharmacological Basis of Therapeutics, 11th edn. New York: McGraw-Hill Professional, 2005.
  • 3
    Grootveld M, Halliwell B. 2,3-Dihydroxybenzoic acid is a product of human aspirin metabolism. Biochem Pharmacol 1988;37:27180.
  • 4
    Chyka PA, Erdman AR, Christianson G et al. Salicylate poisoning: an evidence-based consensus guideline for out-of-hospital management. Clin Toxicol (Phila) 2007;45:95131.
  • 5
    Campbell CL, Smyth S, Montalescot G, Steinhubl SR. Aspirin dose for the prevention of cardiovascular disease. A systematic review. JAMA 2007;297:201824.
  • 6
    Roth GJ, Calverley DC. Aspirin, platelets, and thrombosis: theory and practice. Blood 1994;83:88598.
  • 7
    Berrouschot J, Schwetlick B, von Twickel G et al. Aspirin resistance in secondary stroke prevention. Acta Neurol Scand 2006;113:315.
  • 8
    Krasopoulos G, Brister SJ, Beattie WS, Buchanan MR. Aspirin “resistance” and risk of cardiovascular morbidity: systematic review and meta-analysis. BMJ 2008;336:1958.
  • 9
    Hennekens CH, Schror K, Weisman S, FitzGerald GA. Terms and conditions. Semantic complexity and aspirin resistance. Circulation 2004;110:17068.
  • 10
    Gengo FM, Rainka M, Robson M et al. Prevalence of platelet nonresponsiveness to aspirin in patients treated for secondary stroke prophylaxis and in patients with recurrent ischemic events. J Clin Pharmacol 2008;48:33543.
  • 11
    Sanderson S, Emery J, Baglin T, Kinmonth AL. Narrative review: aspirin resistance and its clinical implications. Ann Int Med 2005;142:37080.
  • 12
    Macchi L, Sorel N, Christiaens L. Aspirin resistance: definitions, mechanisms, prevalence, and clinical significance. Curr Pharm Des 2006;12:2518.
  • 13
    Hankey GJ, Eikelboom JW. Aspirin resistance. Lancet 2006;367:60617.
  • 14
    Wang TH, Bhatt DL, Topol EJ. Aspirin and clopidogrel resistance: an emerging clinical entity. Eur Heart J 2006;27:64754.
  • 15
    Shantsila E, Watson T, Lip GY. Aspirin resistance: what, why and when? Thromb Res 2007;119:5514.
  • 16
    Poulsen TS, Jørgensen B, Korsholm L, Bjørn Licht P, Haghfelt T, Mickley H. Prevalence of aspirin resistance in patients with an evolving acute myocardial infarction. Throm Res 2007;119:55562.
  • 17
    Gum PA, Kottke-Merchant K, Poggio ED et al. Profile and prevalence of aspirin resistance in patients with cardiovascular disease. Am J Cardiol 2001;88:2305.
  • 18
    Kim H, Lee HK, Han K, Jeon HK. Prevalence and risk factors for aspirin and clopidogrel resistance in patients with coronary artery disease or ischemic cerebrovascular disease. Ann Clin Lab Sci 2009;39:28994.
  • 19
    Sztriha LK, Sas K, Seres E et al. Optical platelet aggregometry does not appear useful as a means of assessing the risk of recurrent vascular events in aspirin-treated patients. Acta Neurol Scan 2008;117:2504.
  • 20
    Hart RG, Leonard AD, Talbert RL et al. Aspirin dosage and thromboxane synthesis in patients with vascular disease. Pharmacotherapy 2003;23:57984.
  • 21
    Bruno A, McConnell JP, Cohen SN et al. Serial urinary 11- dehydrothromboxane B2, aspirin dose, and vascular events in blacks after recent cerebral infarction. Stroke 2004;35:72730.
  • 22
    Hovens MM, Snoep JD, Eikenboom JC, van der Bom JG, Mertens BJ, Huisman MV. Prevalence of persistent platelet reactivity despite use of aspirin: a systematic review. Am Heart J 2007;153:17581.
  • 23
    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;90:8935.
  • 24
    Rottlaender D, Scherner M, Schneider T, Erdmann E. Polypharmacy, compliance and non-rescription medication in patients with cardiovascular disease in Germany. Dtsch Med Wochenschr 2007;132:13944.
  • 25
    Gasparyan AY, Watson T, Lip GY. The role of aspirin in cardiovascular prevention: implications of aspirin resistance. J Am Coll Cardiol 2008;51:182943.
  • 26
    Giusti B, Gori AM, Marcucci R et al. Role of glycoprotein Ia gene polymorphisms in determining platelet function in myocardial infarction patients undergoing percutaneous coronary intervention on dual antiplatelet treatment. Atherosclerosis 2008;196:3418.
  • 27
    Zhao YH, Xu Y, Gu YY, Li Y, Zhang JY, Su X. Functional effect of platelet membrane glycoprotein ia gene polymorphism in the pathogenesis of unstable angina pectoris. I Int Med Res 2011;39:5418.
  • 28
    Dropinski J, Musial J, Sanak M, Wegrzyn W, Nizankowski R, Szczeklik A. Antithrombotic effects of aspirin based on PLA1/A2 glycoprotein IIIa polymorphism in patients with coronary artery disease. Thromb Res 2007;119:3013.
  • 29
    Gonzalez-Conejero R, Rivera J, Corral J, Acuña C, Guerrero JA, Vicente V. Biological assessment of aspirin efficacy on healthy individuals: heterogeneous response or aspirin failure? Stroke 2005;36:27680.
  • 30
    Pamukcu B, Oflaz H, Nisanci Y. The role of platelet glycoprotein IIIa polymorphism in the high prevalence of in vitro aspirin resistance in patients with intracoronary stent restenosis. Am Heart J 2005;149:67580.
  • 31
    Kojuri J, Mahmoody Y, Sabegh BZ, Jannati M, Mahboodi A, Khalili A. Dose-related effect of aspirin on laboratory-defined platelet aggregation and clinical outcome after coronary stenting. Cardiovasc Ther 2010;28:14752.
  • 32
    Lansberg MG, O'Donnell MJ, Khatri P et al. Antithrombotic and thrombolytic therapy for ischemic stroke: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012;141(2 Suppl.):e601S36S.
  • 33
    Pena A, Collet JP, Hulot JS et al. Can we override clopidogrel resistance? Circulation 2009;119:28547.
  • 34
    Maree AO, Fitzgerald DJ. Variable platelet response to aspirin and clopidogrel in atherothrombotic disease. Circulation 2007;115:2196207.
  • 35
    Nguyen TA, Diodati JG, Pharand C. Resistance to clopidogrel: a review of the evidence. J Am Coll Cardiol 2005;45:115764.
  • 36
    Mega JL, Close SL, Wiviott SD et al. Cytochrome P-450 polymorphisms and response to clopidogrel. N Engl J Med 2009;360:35462.
  • 37
    Schuldiner AR, O'Connell JR, Bliden KP et al. Association of cytochrome P450 2C19 genotype with the antiplatelet effect and clinical efficacy of clopidogrel therapy. JAMA 2009;302:84957.
  • 38
    Bhatt DL. Tailoring antiplatelet therapy based on pharmacogenomics: how well do the data fit? JAMA 2009;302:8967.
  • 39
    Simon T, Verstuyft C, Mary-Krause M et al. Genetic determinants of response to clopidogrel and cardiovascular events. N Engl J Med 2009;360:36375.
  • 40
    Bristol-Myers Squibb/Sanofi Pharmaceutical Partnership. Plavix (clopidogrel bisulfate) prescribing information. Bridgewater, NJ: Bristol-Myers Squibb/Sanofi Pharmaceuticals Partnership, August 2010. (accessed 18 June 2012).
  • 41
    Paré G, Mehta SR, Yusuf S et al. Effects of CYP2C19 genotype on outcomes of clopidogrel treatment. N Engl J Med 2010;363:170414.
  • 42
    Feher G, Koltai K, Alkonyi B et al. Clopidogrel resistance: role of body mass and concomitant medications. Int J Cardiol 2007;120:18892.
  • 43
    Steinhubl SR, Berger PB, Mann JT 3rd et al. Early and sustained dual oral antiplatelet therapy following percutaneous coronary intervention: a randomized controlled trial. JAMA 2002;288:241120.
  • 44
    Angiolillo DJ, Fernandez-Ortiz A, Bernardo E et al. Variability in individual responsiveness to clopidogrel: clinical implications, management, and future perspectives. J Am Coll Cardiol 2007;49:150516.
  • 45
    Gurbel PA, Bliden KP, Hayes KM, Yoho JA, Herzog WR, Tantry US. The relation of dosing to clopidogrel responsiveness and the incidence of high post-treatment platelet aggregation in patients undergoing coronary stenting. J Am Coll Cardiol 2005;45:13926.
  • 46
    von Beckerath N, Taubert D, Pogatsa-Murray G, Schömig E, Kastrati A, Schömig A. Absorption, metabolization, and antiplatelet effects of 300-, 600-, and 900-mg loading doses of clopidogrel: results of the ISAR-CHOICE (Intracoronary Stenting and Antithrombotic Regimen: Choose Between 3 High Oral Doses for Immediate Clopidogrel Effect) Trial. Circulation 2005;112:294650.
  • 47
    Montalescot G, Sideris G, Meuleman C et al. A randomized comparison of high clopidogrel loading doses in patients with non-ST-segment elevation acute coronary syndromes: the ALBION (Assessment of the Best Loading Dose of Clopidogrel to Blunt Platelet Activation, Inflammation and Ongoing Necrosis) trial. J Am Coll Cardiol 2006;48:9318.
  • 48
    Cuisset T, Frere C, Quilici J et al. Benefit of a 600-mg loading dose of clopidogrel on platelet reactivity and clinical outcomes in patients with non-ST-segment elevation acute coronary syndrome undergoing coronary stenting. J Am Coll Cardiol 2006;48:133945.
  • 49
    Patti G, Colonna G, Pasceri V, Pepe LL, Montinaro A, Di Sciascio G. Randomized trial of high loading dose of clopidogrel for reduction of periprocedural myocardial infarction in patients undergoing coronary intervention: results from the ARMYDA-2 (Antiplatelet therapy for Reduction of MYocardial Damage during Angioplasty) study. Circulation 2005;111:2099106.
  • 50
    Bates ER, Lau WC, Bleske BE. Loading, pretreatment, and interindividual variability issues with clopidogrel dosing. Circulation 2005;111:25579.
  • 51
    Lotrionte M, Biondi-Zoccai GG, Agostoni P et al. Meta-analysis appraising high clopidogrel loading in patients undergoing percutaneous coronary intervention. Am J Cardiol 2007;100:1199206.
  • 52
    Biondi-Zoccai GG, Lotrionte M, Agostoni P et al. Benefits of clopidogrel in patients undergoing coronary stenting significantly depend on loading dose: evidence from a meta-regression. Am Heart J 2007;153:58793.
  • 53
    Wiviott SD, Braunwald E, McCabe CH et al. Prasugrel versus clopidogrel in patients with acute coronary syndromes. N Engl J Med 2007;357:200115.
  • 54
    Wiviott SD, Braunwald E, Angiolillo DJ et al. Greater clinical benefit of more intensive oral antiplatelet therapy with prasugrel in patients with diabetes mellitus in the trial to assess improvement in therapeutic outcomes by optimizing platelet inhibition with prasugrel-Thrombolysis in Myocardial Infarction. Circulation 2008;118:162636.
  • 55
    Sabatine MS. Novel antiplatelet strategies in acute coronary syndromes. Cleve Clin J Med 2009;76:S815.
  • 56
    Smyth SS, Woulfe DS, Weitz JI et al. G-protein-coupled receptors as signaling targets for antiplatelet therapy. Arterioscler Thromb Vasc Biol 2009;29:44957.
  • 57
    Wright CB, Moon Y, Paik MC et al. Inflammatory biomarkers of vascular risk as correlates of leukoariosis. Stroke 2009;40:346671.
  • 58
    Furie KL, Kasner SE, Adams RJ et al. Guidelines for the prevention of stroke in patients with stroke or transient ischemic attack: a guideline for healthcare professionals from the american heart association/american stroke association. Stroke 2011;43:22776.