Antiplatelet therapy in acute coronary syndromes

Journal of Cardiovascular Pharmacology and Therapeutics

Volumn 16, Issue 1, 2011, Pages 24-42

  Aragam, Krishna G ^a   Bhatt, Deepak L ^b  

^a UNIVERSITY OF MICHIGAN   (United States)

^b HARVARD MEDICAL SCHOOL   (United States)

Author keywords

acute coronary syndrome; antiplatelet therapy; aspirin; clopidogrel; glycoprotein IIb IIIa inhibitor

Indexed keywords

3A,4,4A,5,6,7,8,8A,9,9A DECAHYDRO N [4 [2 [5 (3 FLUOROPHENYL) 2 PYRIDYL]VINYL] 3 METHYL 1 OXO 3H BENZO[F]ISOBENZOFURAN 7 YL]CARBAMIC ACID ETHYL ESTER; ABCIXIMAB; ACETYLSALICYLIC ACID; ANTITHROMBOCYTIC AGENT; ATORVASTATIN; CANGRELOR; CGT 2168; CLOPIDOGREL; E 5555; ELINOGREL; ERYTHROMYCIN; HIRULOG; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; METOPROLOL; OMEPRAZOLE; PLACEBO; PRASUGREL; PROTEINASE ACTIVATED RECEPTOR 1; PROTON PUMP INHIBITOR; RIFAMPICIN; SCH 5348; THIENOPYRIDINE DERIVATIVE; THROMBIN INHIBITOR; THROMBIN RECEPTOR ANTAGONIST; TICAGRELOR; TICLOPIDINE; UNCLASSIFIED DRUG; WARFARIN;

ACUTE CORONARY SYNDROME; ANGIOCARDIOGRAPHY; ANTICOAGULANT THERAPY; ARTICLE; BLEEDING; BRAIN HEMORRHAGE; BRAIN ISCHEMIA; CARDIOVASCULAR RISK; CREATININE BLOOD LEVEL; DRUG DOSE COMPARISON; DRUG EFFICACY; DRUG MEGADOSE; DRUG POTENCY; DRUG SAFETY; DRUG WITHDRAWAL; DYSPNEA; FIBRINOLYTIC THERAPY; FOLLOW UP; GASTROINTESTINAL HEMORRHAGE; GENETIC POLYMORPHISM; GENETIC VARIABILITY; GENOTYPE; HEART INFARCTION; HIGH RISK PATIENT; HOSPITAL READMISSION; HUMAN; LOADING DRUG DOSE; LONG TERM CARE; LOSS OF FUNCTION MUTATION; LOW DRUG DOSE; MAINTENANCE DRUG DOSE; NON ST SEGMENT ELEVATION MYOCARDIAL INFARCTION; OUTCOME ASSESSMENT; PERCUTANEOUS CORONARY INTERVENTION; PERIPHERAL OCCLUSIVE ARTERY DISEASE; POINT OF CARE TESTING; PRIORITY JOURNAL; RISK REDUCTION; SIDE EFFECT; SINGLE DRUG DOSE; ST SEGMENT ELEVATION MYOCARDIAL INFARCTION; STENT THROMBOSIS; STROKE; THROMBOCYTE ACTIVATION; THROMBOCYTE AGGREGATION; TRANSIENT ISCHEMIC ATTACK; TREATMENT DURATION; TREATMENT RESPONSE; URIC ACID BLOOD LEVEL;

ACUTE CORONARY SYNDROME; ANGIOPLASTY; ASPIRIN; DRUG INTERACTIONS; HUMANS; MEDICATION ADHERENCE; PLATELET AGGREGATION INHIBITORS; PLATELET GLYCOPROTEIN GPIIB-IIIA COMPLEX; PURINERGIC P2Y RECEPTOR ANTAGONISTS; THROMBOSIS;

EID: 79951470134     PISSN: 10742484     EISSN: 19404034     Source Type: Journal    
DOI: 10.1177/1074248410381758     Document Type: Article

References (137)

1. American Heart Association. Heart Disease and Stroke Statistics- 2009 Update. Dallas, Texas: American Heart Association ; 2009.
2. Meadows TA, Bhatt DL Clinical aspects of platelet inhibitors and thrombus formation. Circ Res. 2007 ; 100 (9). 1261-1275. (Pubitemid 46742917)
3. Anderson JL, Adams CD, Antman EM, et al. ACC/AHA 2007 guidelines for the management of patients with UA/non ST-elevation myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 2002 Guidelines for the Management of Patients With Unstable Angina/Non ST-Elevation Myocardial Infarction): developed in collaboration with the American College of Emergency Physicians, the Society for Cardiovascular Angiography and Interventions, and the Society of Thoracic Surgeons: endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation and the Society for Academic Emergency Medicine. Circulation. 2007;116(7):e148-e304.
4. Roth GJ, Majerus PW The mechanism of the effect of aspirin on human platelets. I. Acetylation of a particulate fraction protein. J Clin Invest. 1975 ; 56 (3). 624-632.
5. Cairns JA, Gent M., Singer J., et al. Aspirin, sulfinpyrazone, or both in unstable angina. Results of a Canadian multicenter trial. N Engl J Med. 1985 ; 313 (22). 1369-1375. (Pubitemid 16211835)
6. Lewis HD Jr, Davis JW, Archibald DG, et al. Protective effects of aspirin against acute myocardial infarction and death in men with unstable angina. Results of a Veterans Administration Cooperative Study. N Engl J Med. 1983 ; 309 (7). 396-403.
7. Theroux P., Ouimet H., McCans J., et al. Aspirin, heparin, or both to treat acute unstable angina. N Engl J Med. 1988 ; 319 (17). 1105-1111.
8. Risk of myocardial infarction and death during treatment with low dose aspirin and intravenous heparin in men with unstable coronary artery disease. The RISC Group. Lancet. 1990 ; 336 (8719). 827-830.
9. Wallentin LC Aspirin (75 mg/day) after an episode of unstable coronary artery disease: long-term effects on the risk for myocardial infarction, occurrence of severe angina and the need for revascularization. Research Group on Instability in Coronary Artery Disease in Southeast Sweden. J Am Coll Cardiol. 1991 ; 18 (7). 1587-1593.
10. 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 (7329). 71-86.
11. Peters RJ, Mehta SR, Fox KA, et al. Effects of aspirin dose when used alone or in combination with clopidogrel in patients with acute coronary syndromes: observations from the Clopidogrel in Unstable angina to prevent Recurrent Events (CURE) study. Circulation. 2003 ; 108 (14). 1682-1687. (Pubitemid 37243654)
12. Topol EJ, Easton D., Harrington RA, et al. Randomized, double-blind, placebo-controlled, international trial of the oral IIb/IIIa antagonist lotrafiban in coronary and cerebrovascular disease. Circulation. 2003 ; 108 (4). 399-406. (Pubitemid 36935531)
13. Mehta SR, Bassand JP, Chrolavicius S., et al. Design and rationale of CURRENT-OASIS 7: a randomized, 2 x 2 factorial trial evaluating optimal dosing strategies for clopidogrel and aspirin in patients with ST and non-ST-elevation acute coronary syndromes managed with an early invasive strategy. Am Heart J. 2008 ; 156 (6). 1080.e1-1088e1.
14. Mehta SR CURRENT-OASIS 7: A 2x2 Factorial Randomized Trial of Optimal Clopidogrel and Aspirin Dosing in Patients with ACS Undergoing an Early Invasive Strategy with Intent for PCI. Barcelona, Spain: European Society of Cardiology Congress ; 2009.
15. Storey RF, Sanderson HM, White AE, May JA, Cameron KE, Heptinstall S. The central role of the P(2T) receptor in amplification of human platelet activation, aggregation, secretion and pro-coagulant activity. Br J Haematol. 2000 ; 110 (4). 925-934.
16. Thebault JJ, Blatrix CE, Blanchard JF, Panak EA Effects of ticlopidine, a new platelet aggregation inhibitor in man. Clin Pharmacol Ther. 1975 ; 18 (4). 485-490.
17. Balsano F., Rizzon P., Violi F., et al. Antiplatelet treatment with ticlopidine in unstable angina. A controlled multicenter clinical trial. The Studio della Ticlopidina nell'Angina Instabile Group. Circulation. 1990 ; 82 (1). 17-26. (Pubitemid 20216311)
18. Scrutinio D., Cimminiello C., Marubini E., Pitzalis MV, Di Biase M., Rizzon P. Ticlopidine versus aspirin after myocardial infarction (STAMI) trial. J Am Coll Cardiol. 2001 ; 37 (5). 1259-1265.
19. Hall P., Nakamura S., Maiello L., et al. A randomized comparison of combined ticlopidine and aspirin therapy versus aspirin therapy alone after successful intravascular ultrasound-guided stent implantation. Circulation. 1996 ; 93 (2). 215-222. (Pubitemid 26031477)
20. Urban P., Macaya C., Rupprecht HJ, et al. Randomized evaluation of anticoagulation versus antiplatelet therapy after coronary stent implantation in high-risk patients: the multicenter aspirin and ticlopidine trial after intracoronary stenting (MATTIS). Circulation. 1998 ; 98 (20). 2126-2132. (Pubitemid 28527471)
21. Schomig A., Neumann FJ, Kastrati A., et al. A randomized comparison of antiplatelet and anticoagulant therapy after the placement of coronary-artery stents. N Engl J Med. 1996 ; 334 (17). 1084-1089. (Pubitemid 26120185)
22. Leon MB, Baim DS, Popma JJ, et al. A clinical trial comparing three antithrombotic-drug regimens after coronary-artery stenting. Stent Anticoagulation Restenosis Study Investigators. N Engl J Med. 1998 ; 339 (23). 1665-1671. (Pubitemid 28550691)
23. Bertrand ME, Legrand V., Boland J., et al. Randomized multicenter comparison of conventional anticoagulation versus antiplatelet therapy in unplanned and elective coronary stenting. The full anticoagulation versus aspirin and ticlopidine (fantastic) study. Circulation. 1998 ; 98 (16). 1597-1603. (Pubitemid 28500380)
24. Steinhubl SR, Tan WA, Foody JM, Topol EJ Incidence and clinical course of thrombotic thrombocytopenic purpura due to ticlopidine following coronary stenting. EPISTENT Investigators. Evaluation of Platelet IIb/IIIa Inhibitor for Stenting. JAMA. 1999 ; 281 (9). 806-810. (Pubitemid 29113740)
25. Bertrand ME, Rupprecht HJ, Urban P., Gershlick AH Double-blind study of the safety of clopidogrel with and without a loading dose in combination with aspirin compared with ticlopidine in combination with aspirin after coronary stenting: the clopidogrel aspirin stent international cooperative study (CLASSICS). Circulation. 2000 ; 102 (6). 624-629. (Pubitemid 30640661)
26. Bhatt DL, Bertrand ME, Berger PB, et al. Meta-analysis of randomized and registry comparisons of ticlopidine with clopidogrel after stenting. J Am Coll Cardiol. 2002 ; 39 (1). 9-14. (Pubitemid 34059855)
27. A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). CAPRIE Steering Committee. Lancet. 1996 ; 348 (9038). 1329-1339.
28. Bhatt DL, Marso SP, Hirsch AT, Ringleb PA, Hacke W., Topol EJ Amplified benefit of clopidogrel versus aspirin in patients with diabetes mellitus. Am J Cardiol. 2002 ; 90 (6). 625-628. (Pubitemid 35264538)
29. Bhatt DL, Chew DP, Hirsch AT, Ringleb PA, Hacke W., Topol EJ Superiority of clopidogrel versus aspirin in patients with prior cardiac surgery. Circulation. 2001 ; 103 (3). 363-368. (Pubitemid 32105974)
30. Ringleb PA, Bhatt DL, Hirsch AT, Topol EJ, Hacke W. Benefit of clopidogrel over aspirin is amplified in patients with a history of ischemic events. Stroke. 2004 ; 35 (2). 528-532. (Pubitemid 38174442)
31. Yusuf S., Zhao F., Mehta SR, Chrolavicius S., Tognoni G., Fox KK Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation. N Engl J Med. 2001 ; 345 (7). 494-502. (Pubitemid 32758501)
32. Mehta SR, Yusuf S., Peters RJ, et al. 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 (9281). 527-533. (Pubitemid 32772726)
33. 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 (19). 2411-2420. (Pubitemid 35340537)
34. Steinhubl SR, Berger PB, Brennan DM, Topol EJ Optimal timing for the initiation of pre-treatment with 300 mg clopidogrel before percutaneous coronary intervention. J Am Coll Cardiol. 2006 ; 47 ( 50: 939-943.
35. Byrne RA, Schulz S., Mehilli J., et al. Rationale and design of a randomized, double-blind, placebo-controlled trial of 6 versus 12 months clopidogrel therapy after implantation of a drug-eluting stent: The Intracoronary Stenting and Antithrombotic Regimen: Safety And EFficacy of 6 Months Dual Antiplatelet Therapy After Drug-Eluting Stenting (ISAR-SAFE) study. Am Heart J. 2009 ; 157 (4). 620e2-624e2.
36. Sabatine MS, Cannon CP, Gibson CM, et al. Addition of clopidogrel to aspirin and fibrinolytic therapy for myocardial infarction with ST-segment elevation. N Engl J Med. 2005 ; 352 (12). 1179-1189. (Pubitemid 40397259)
37. Sabatine MS, Cannon CP, Gibson CM, et al. Effect of clopidogrel pretreatment before percutaneous coronary intervention in patients with ST-elevation myocardial infarction treated with fibrinolytics: the PCI-CLARITY study. JAMA. 2005 ; 294 (10). 1224-1232. (Pubitemid 41352110)
38. Chen ZM, Jiang LX, Chen YP, et al. Addition of clopidogrel to aspirin in 45,852 patients with acute myocardial infarction: randomised placebo-controlled trial. Lancet. 2005 ; 366 (9497). 1607-1621.
39. Bhatt DL, Fox KA, Hacke W., et al. Clopidogrel and aspirin versus aspirin alone for the prevention of atherothrombotic events. N Engl J Med. 2006 ; 354 (16). 1706-1717.
40. Bhatt DL, Flather MD, Hacke W., et al. Patients with prior myocardial infarction, stroke, or symptomatic peripheral arterial disease in the CHARISMA trial. J Am Coll Cardiol. 2007 ; 49 (19). 1982-1988. (Pubitemid 46694290)
41. Wiviott SD Clopidogrel response variability, resistance, or both? Am J Cardiol. 2006 ; 98 (10A). 18N - 24N.
42. Michelson AD Platelet function testing in cardiovascular diseases. Circulation. 2004 ; 110 (19). e489 - e493.
43. Michelson AD, Frelinger AL 3rd, Furman MI Current options in platelet function testing. Am J Cardiol. 2006 ; 98 (10A). 4N - 10N.
44. 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 (23). 2908-2913. (Pubitemid 36736631)
45. Muller I., Besta F., Schulz C., Massberg S., Schonig A., Gawaz M. Prevalence of clopidogrel non-responders among patients with stable angina pectoris scheduled for elective coronary stent placement. Thromb Haemost. 2003 ; 89 (5). 783-787. (Pubitemid 36603418)
46. Serebruany VL, Steinhubl SR, Berger PB, Malinin AI, Bhatt DL, Topol EJ Variability in platelet responsiveness to clopidogrel among 544 individuals. J Am Coll Cardiol. 2005 ; 45 (2). 246-251. (Pubitemid 40094733)
47. 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 (25). 3171-3175.
48. Gurbel PA, Bliden KP, Samara W., et al. Clopidogrel effect on platelet reactivity in patients with stent thrombosis: results of the CREST Study. J Am Coll Cardiol. 2005 ; 46 (10). 1827-1832. (Pubitemid 41579803)
49. Kurihara A., Hagihara K., Kazui M., Ozeki T., Farid N., Ikeda T. In vitro metabolism of antiplatelet agent clopidogrel: cytochrome P450 isoforms responsible for two oxidation steps involved in the active metabolite formation. Drug Metab Rev. 2005 ; 37 (suppl2). 99.
50. Lau WC, Waskell LA, Watkins PB, et al. Atorvastatin reduces the ability of clopidogrel to inhibit platelet aggregation: a new drug-drug interaction. Circulation. 2003 ; 107: 32-37. (Pubitemid 36070929)
51. Neubauer H., Gunesdogan B., Hanefeld C., Spiecker M., Mugge A. Lipophilic statins interfere with the inhibitory effects of clopidogrel on platelet function-a flow cytometry study. Eur Heart J. 2003 ; 24 (19). 1744-1749. (Pubitemid 37236863)
52. Muller 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 (18). 2195-2197. (Pubitemid 37363034)
53. 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 (11). 1335-1338. (Pubitemid 38387816)
54. Serebruany VL, Midei MG, Malinin AI, et al. Absence of interaction between atorvastatin or other statins and clopidogrel: results from the interaction study. Arch Intern Med. 2004 ; 164 (18). 2051-2057. (Pubitemid 39390564)
55. Vinholt P., Poulsen TS, Korsholm L., et al. The antiplatelet effect of clopidogrel is not attenuated by statin treatment in stable patients with ischemic heart disease. Thromb Haemost. 2005 ; 94: 438-443. (Pubitemid 41122501)
56. Saw J., Brennan DM, Steinhubl SR, et al. Lack of evidence of a clopidogrel-statin interaction in the CHARISMA trial. J Am Coll Cardiol. 2007 ; 50 (4). 291-295. (Pubitemid 47058889)
57. Li XQ, Andersson TB, Ahlstrom M., Weidolf L. Comparison of inhibitory effects of the proton pump-inhibiting drugs omeprazole, esomeprazole, lansoprazole, pantoprazole, and rabeprazole on human cytochrome P450 activities. Drug Metab Dispos. 2004 ; 32 (8). 821-827. (Pubitemid 38955611)
58. Ho PM, Maddox TM, Wang L., et al. Risk of adverse outcomes associated with concomitant use of clopidogrel and proton pump inhibitors following acute coronary syndrome. JAMA. 2009 ; 301 (9). 937-944.
59. Rassen JA, Choudhry NK, Avorn J., Schneeweiss S. Cardiovascular outcomes and mortality in patients using clopidogrel with proton pump inhibitors after percutaneous coronary intervention or acute coronary syndrome. Circulation. 2009 ; 120 (23). 2322-2329.
60. O'Donoghue ML, Braunwald E., Antman EM, et al. Pharmacodynamic effect and clinical efficacy of clopidogrel and prasugrel with or without a proton-pump inhibitor: an analysis of two randomised trials. Lancet. 2009 ; 374 (9694). 989-997.
61. Bhatt DL The Clopidogrel and the Optimization of Gastrointestinal Events (COGENT) trial. Transcatheter Cardiovascular Therapeutics Conference. San Francisco, CA, 2009.
62. Depta JP, Bhatt DL Omeprazole and clopidogrel: Should clinicians be worried? Cleve Clin J Med. 2010 ; 77 (2). 113-116.
63. Kim KA, Park PW, Hong SJ, Park JY The effect of CYP2C19 polymorphism on the pharmacokinetics and pharmacodynamics of clopidogrel: a possible mechanism for clopidogrel resistance. Clin Pharmacol Ther. 2008 ; 84 (2). 236-242.
64. Mega JL, Close SL, Wiviott SD, et al. Cytochrome p-450 polymorphisms and response to clopidogrel. N Engl J Med. 2009 ; 360 (21). 354-362.
65. Collet JP, Hulot JS, Pena A., et al. Cytochrome P450 2C19 polymorphism in young patients treated with clopidogrel after myocardial infarction: a cohort study. Lancet. 2009 ; 373 (9660). 309-317.
66. Trenk D., Hochholzer W., Fromm MF, et al. Cytochrome P450 2C19 681G>A polymorphism and high on-clopidogrel platelet reactivity associated with adverse 1-year clinical outcome of elective percutaneous coronary intervention with drug-eluting or bare-metal stents. J Am Coll Cardiol. 2008 ; 51 (20). 1925-1934. (Pubitemid 351636443)
67. Simon T., Verstuyft C., Mary-Krause M., et al. Genetic determinants of response to clopidogrel and cardiovascular events. N Engl J Med. 2009 ; 360 (4). 363-375.
68. Shuldiner 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 (8). 849-857.
69. Bhatt DL Charisma Genomics SUBSTUDY: Evaluation of the CYP2C19 Polymorphism in a Prospective, Randomized, Placebo-Controlled Trial of Chronic Clopidogrel Use for Primary and Secondary Prevention. Transcatheter Cardiovascular Therapeutics Conference. San Francisco, CA, 2009.
70. Breet NJ, van Werkum JW, Bouman HJ, et al. Comparison of platelet function tests in predicting clinical outcome in patients undergoing coronary stent implantation. JAMA. 2010 ; 303 (8). 754-762.
71. Price MJ, Berger PB, Angiolillo DJ, et al. Evaluation of individualized clopidogrel therapy after drug-eluting stent implantation in patients with high residual platelet reactivity: design and rationale of the GRAVITAS trial. Am Heart J. 2009 ; 157 (5). 818-824, 824e1.
72. Bhatt DL Tailoring antiplatelet therapy based on pharmacogenomics: how well do the data fit? JAMA. 2009 ; 302 (8). 896-897.
73. 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 (9). 1392-1396. (Pubitemid 40615608)
74. von Beckerath N., Taubert D., Pogatsa-Murray G., Schomig E., Kastrati A., Schomig 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 (19). 2946-2950. (Pubitemid 41612296)
75. 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 (16). 2099-2106. (Pubitemid 40577905)
76. 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 (7). 1339-1345. (Pubitemid 44436814)
77. von Beckerath N., Kastrati A., Wieczorek A., et al. A double-blind, randomized study on platelet aggregation in patients treated with a daily dose of 150 or 75 mg of clopidogrel for 30 days. Eur Heart J. 2007 ; 28 (15). 1814-1819. (Pubitemid 47236637)
78. Angiolillo DJ, Shoemaker SB, Desai B., et al. Randomized comparison of a high clopidogrel maintenance dose in patients with diabetes mellitus and coronary artery disease: results of the Optimizing Antiplatelet Therapy in Diabetes Mellitus (OPTIMUS) study. Circulation. 2007 ; 115 (6). 708-716. (Pubitemid 46294761)
79. Asai F., Jakubowski JA, Naganuma H., et al. Platelet inhibitory activity and pharmacokinetics of prasugrel (CS-747) a novel thienopyridine P2Y12 inhibitor: a single ascending dose study in healthy humans. Platelets. 2006 ; 17 (4). 209-217. (Pubitemid 43890792)
80. Jernberg T., Payne CD, Winters KJ, et al. Prasugrel achieves greater inhibition of platelet aggregation and a lower rate of non-responders compared with clopidogrel in aspirin-treated patients with stable coronary artery disease. Eur Heart J. 2006 ; 27 (10). 1166-1173.
81. Brandt JT, Payne CD, Wiviott SD, et al. A comparison of prasugrel and clopidogrel loading doses on platelet function: magnitude of platelet inhibition is related to active metabolite formation. Am Heart J. 2007 ; 153 (1). 66e9-66e16.
82. Wiviott SD, Braunwald E., McCabe CH, et al. Prasugrel versus clopidogrel in patients with acute coronary syndromes. N Engl J Med. 2007 ; 357 (20). 2001-2015. (Pubitemid 350106708)
83. 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 38. Circulation. 2008 ; 118 (16). 1626-1636.
84. 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 (19). 2553-2560.
85. Mahoney EM, Wang K., Arnold SV, et al. Cost-effectiveness of prasugrel versus clopidogrel in patients with acute coronary syndromes and planned percutaneous coronary intervention: results from the trial to assess improvement in therapeutic outcomes by optimizing platelet inhibition with Prasugrel-Thrombolysis in Myocardial Infarction TRITON-TIMI 38. Circulation. 2010 ; 121 (1). 71-79.
86. Storey RF, Husted S., Harrington RA, 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 (19). 1852-1856. (Pubitemid 350017792)
87. 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 (9). 1038-1047.
88. Cannon CP, Husted S., Harrington RA, et al. 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 (19). 1844-1851. (Pubitemid 350007959)
89. Wallentin L., Becker RC, Budaj A., et al. Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med. 2009 ; 361 (11). 1045-1057.
90. Boersma E., Harrington RA, Moliterno DJ, et al. Platelet glycoprotein IIb/IIIa inhibitors in acute coronary syndromes: a meta-analysis of all major randomised clinical trials. Lancet. 2002 ; 359 (9302). 189-198. (Pubitemid 34113814)
91. Cannon CP, Harrington RA, James S., et al. Comparison of ticagrelor with clopidogrel in patients with a planned invasive strategy for acute coronary syndromes (PLATO): a randomised double-blind study. Lancet. 2010 ; 375 (9711). 283-293.
92. Alexander D., Ou FS, Roe MT, et al. Use of and inhospital outcomes after early clopidogrel therapy in patients not undergoing an early invasive strategy for treatment of non-ST-segment elevation myocardial infarction: results from Can Rapid risk stratification of Unstable angina patients Suppress ADverse outcomes with Early implementation of the American College of Cardiology/American Heart Association guidelines (CRUSADE). Am Heart J. 2008 ; 156 (3). 606-612.
93. Fugate SE, Cudd LA Cangrelor for treatment of coronary thrombosis. Ann Pharmacother. 2006 ; 40 (5). 925-930. (Pubitemid 43765010)
94. Greenbaum AB, Grines CL, Bittl JA, et al. Initial experience with an intravenous P2Y12 platelet receptor antagonist in patients undergoing percutaneous coronary intervention: results from a 2-part, phase II, multicenter, randomized, placebo- and active-controlled trial. Am Heart J. 2006 ; 151 (3). 689e1-689e10.
95. Harrington RA, Stone GW, McNulty S., et al. Platelet inhibition with cangrelor in patients undergoing PCI. N Engl J Med. 2009 ; 361 (24). 2318-2329.
96. Bhatt DL, Lincoff AM, Gibson CM, et al. Intravenous platelet blockade with cangrelor during PCI. N Engl J Med. 2009 ; 361 (24). 2330-2341.
97. Gurbel PA, Bliden KP, Antonino MJ, et al. The effect of elinogrel on high platelet reactivity during dual antiplatelet therapy and the relation to CYP2C19*2 genotype: first experience in patients. J Thromb Haemost. 2010 ; 8 (1). 43-53.
98. Berger JS, Roe MT, Gibson CM, et al. Safety and feasibility of adjunctive antiplatelet therapy with intravenous elinogrel, a direct-acting and reversible P2Y12 ADP-receptor antagonist, before primary percutaneous intervention in patients with ST-elevation myocardial infarction: the Early Rapid ReversAl of platelet thromboSis with intravenous Elinogrel before PCI to optimize reperfusion in acute Myocardial Infarction (ERASE MI) pilot trial. Am Heart J. 2009 ; 158 (6). 998.e1-1004.e1.
99. Steinhubl SR, Oh JJ, Oestreich JH, Ferraris S., Charnigo R., Akers WS Transitioning patients from cangrelor to clopidogrel: pharmacodynamic evidence of a competitive effect. Thromb Res. 2008 ; 121 (4). 527-534. (Pubitemid 351174272)
100. A Phase 2 Safety and Efficacy Study of PRT060128, a Novel Intravenous and Oral P2Y12 Inhibitor, in Non-Urgent PCI (INNOVATE-PCI) trial. http://www.clinicaltrials.gov:Identifier:NCT00751231. Accessed: February 5, 2010.
101. Simoons ML Effect of glycoprotein IIb/IIIa receptor blocker abciximab on outcome in patients with acute coronary syndromes without early coronary revascularisation: the GUSTO IV-ACS randomised trial. Lancet. 2001 ; 357 (9272). 1915-1924. (Pubitemid 32568331)
102. Dauerman HL, Frederick PD, Miller D., French WJ Current incidence and clinical outcomes of bivalirudin administration among patients undergoing primary coronary intervention for stent thrombosis elevation acute myocardial infarction. Coron Artery Dis. 2007 ; 18 (2). 141-148.
103. Montalescot G., Barragan P., Wittenberg O., et al. Platelet glycoprotein IIb/IIIa inhibition with coronary stenting for acute myocardial infarction. N Engl J Med. 2001 ; 344 (25). 1895-1903. (Pubitemid 32553358)
104. Stone GW, Grines CL, Cox DA, et al. Comparison of angioplasty with stenting, with or without abciximab, in acute myocardial infarction. N Engl J Med. 2002 ; 346: 957-966. (Pubitemid 34983245)
105. De Luca G., Suryapranata H., Stone GW, et al. Abciximab as adjunctive therapy to reperfusion in acute ST-segment elevation myocardial infarction: a meta-analysis of randomized trials. JAMA. 2005 ; 293 (14). 1759-1765.
106. Kastrati A., Mehilli J., Neumann FJ, et al. Abciximab in patients with acute coronary syndromes undergoing percutaneous coronary intervention after clopidogrel pretreatment: the ISAR-REACT 2 randomized trial. JAMA. 2006 ; 295 (13). 1531-1518.
107. O'Donoghue M., Antman EM, Braunwald E., et al. The efficacy and safety of prasugrel with and without a glycoprotein IIb/IIIa inhibitor in patients with acute coronary syndromes undergoing percutaneous intervention: a TRITON-TIMI 38 (Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition With Prasugrel-Thrombolysis In Myocardial Infarction 38) analysis. J Am Coll Cardiol. 2009 ; 54 (8). 678-685.
108. Primary versus tenecteplase-facilitated percutaneous coronary intervention in patients with ST-segment elevation acute myocardial infarction (ASSENT-4 PCI): randomised trial. Lancet. 2006 ; 367 (9510). 569-578.
109. Antman EM, Giugliano RP, Gibson CM, et al. Abciximab facilitates the rate and extent of thrombolysis: results of the thrombolysis in myocardial infarction (TIMI) 14 trial. The TIMI 14 Investigators. Circulation. 1999 ; 99 (21). 2720-2732. (Pubitemid 29250016)
110. de Lemos JA, Antman EM, Gibson CM, et al. Abciximab improves both epicardial flow and myocardial reperfusion in ST-elevation myocardial infarction. Observations from the TIMI 14 trial. Circulation. 2000 ; 101 (3). 239-243. (Pubitemid 30054149)
111. Trial of abciximab with and without low-dose reteplase for acute myocardial infarction. Strategies for Patency Enhancement in the Emergency Department (SPEED) Group. Circulation. 2000 ; 101 (24). 2788-2794.
112. Ellis SG, Tendera M., de Belder MA, et al. Facilitated PCI in patients with ST-elevation myocardial infarction. N Engl J Med. 2008 ; 358: 2205-2217. (Pubitemid 351724450)
113. Giugliano RP, White JA, Bode C., et al. Early versus delayed, provisional eptifibatide in acute coronary syndromes. N Engl J Med. 2009 ; 360 (21). 2176-2190.
114. Chew DP, Bhatt DL, Sapp S., Topol EJ Increased mortality with oral platelet glycoprotein IIb/IIIa antagonists: a meta-analysis of phase III multicenter randomized trials. Circulation. 2001 ; 103 (2). 201-206. (Pubitemid 32095403)
115. Coughlin SR Protease-activated receptors in hemostasis, thrombosis and vascular biology. J Thromb Haemost. 2005 ; 3 (8). 1800-1814. (Pubitemid 41716567)
116. Chackalamannil S., Wang Y., Greenlee WJ, et al. Discovery of a novel, orally active himbacine-based thrombin receptor antagonist (SCH 530348) with potent antiplatelet activity. J Med Chem. 2008 ; 51 (11). 3061-3064. (Pubitemid 351821864)
117. Chintala M., Vemulapalli S., Kurowski S., et al. SCH 530348, a novel oral antiplatelet agent, demonstrated no bleeding risk alone or in combination with aspirin and clopidogrel in cynomolgus monkeys. Atheroscler Thromb Vasc Biol. 2008 ; 28: e32 - e149. Abstract P579.
118. Kosoglou T., Reyderman L., Kasserra C., et al. Optimizing dose of the novel thrombin receptor antagonist SCH 530348 based on pharmacodynamics and pharmacokinetics in healthy subjects. Clin Pharmacol Ther. 2008 ; 83 Suppl1: S55.
119. Kosoglou T., Tiessen R., Van Vliet AA, Fales RR, Keller R., Cutler DL Safety and tolerability of SCH 530348, a novel antiplatelet agent, after single and multiple oral dosing in healthy subjects. Eur Heart J. 2008 ; 29 Suppl abstr: 201. Abstract P1340.
120. Becker RC, Moliterno DJ, Jennings LK, et al. Safety and tolerability of SCH 530348 in patients undergoing non-urgent percutaneous coronary intervention: a randomised, double-blind, placebo-controlled phase II study. Lancet. 2009 ; 373 (9667). 919-928.
121. Morrow DA, Scirica BM, Fox KA, et al. Evaluation of a novel antiplatelet agent for secondary prevention in patients with a history of atherosclerotic disease: design and rationale for the Thrombin-Receptor Antagonist in Secondary Prevention of Atherothrombotic Ischemic Events (TRA 2 degrees P)-TIMI 50 trial. Am Heart J. 2009 ; 158 (3). 335.e3-341.e3.
122. The Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome (TRA*CER) trial: study design and rationale. Am Heart J. 2009 ; 158 ( 3 )s: 327.e4-334.e4.
123. Chackalamannil S. Thrombin receptor (protease activated receptor-1) antagonists as potent antithrombotic agents with strong antiplatelet effects. J Med Chem. 2006 ; 49 (18). 5389-5403. (Pubitemid 44373171)
124. Serebruany VL, Kogushi M., Dastros-Pitei D., Flather M., Bhatt DL The in-vitro effects of E5555, a protease-activated receptor (PAR)-1 antagonist, on platelet biomarkers in healthy volunteers and patients with coronary artery disease. Thromb Haemost. 2009 ; 102 (1). 111-119.
125. Safety and tolerability of E5555 and its effects on markers of intravascular inflammation in subjects with coronary artery disease. http://www.clinicaltrials.gov:Identifier:NCT00312052. Accessed February 6, 2010.
126. Safety and tolerability of E5555 and its effects on markers of intravascular inflammation in subjects with acute coronary syndrome. http://www.clinicaltrials.gov:Identifier:NCT00548587. Accessed February 6, 2010.
127. Bhatt DL, Steg PG, Ohman EM, et al. International prevalence, recognition, and treatment of cardiovascular risk factors in outpatients with atherothrombosis. JAMA. 2006 ; 295 (2). 180-189. (Pubitemid 43076437)
128. Iakovou I., Schmidt T., Bonizzoni E., et al. Incidence, predictors, and outcome of thrombosis after successful implantation of drug-eluting stents. JAMA. 2005 ; 293 (17). 2126-2130. (Pubitemid 40617065)
129. Jeremias A., Sylvia B., Bridges J., et al. Stent thrombosis after successful sirolimus-eluting stent implantation. Circulation. 2004 ; 109 (16). 1930-1932. (Pubitemid 38544480)
130. Spertus JA, Kettelkamp R., Vance C., et al. Prevalence, predictors, and outcomes of premature discontinuation of thienopyridine therapy after drug-eluting stent placement: results from the PREMIER registry. Circulation. 2006 ; 113 (24). 2803-2809. (Pubitemid 44305292)
131. Pfisterer M., Brunner-La Rocca HP, Buser PT, et al. Late clinical events after clopidogrel discontinuation may limit the benefit of drug-eluting stents: an observational study of drug-eluting versus bare-metal stents. J Am Coll Cardiol. 2006 ; 48 (12). 2584-2591. (Pubitemid 44881238)
132. Ho PM, Peterson ED, Wang L., et al. Incidence of death and acute myocardial infarction associated with stopping clopidogrel after acute coronary syndrome. JAMA. 2008 ; 299 (5). 532-539. (Pubitemid 351222546)
133. Sibbing D., Stegherr J., Braun S., et al. A double-blind, randomized study on prevention and existence of a rebound phenomenon of platelets after cessation of clopidogrel treatment. J Am Coll Cardiol. 2010 ; 55 (6). 558-565.
134. Valerin MA, Brennan MT, Noll JL, et al. Relationship between aspirin use and postoperative bleeding from dental extractions in a healthy population. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2006 ; 102: 326.
135. Grines CL, Bonow RO, Casey DE Jr, et al. Prevention of premature discontinuation of dual antiplatelet therapy in patients with coronary artery stents: a science advisory from the American Heart Association, American College of Cardiology, Society for Cardiovascular Angiography and Interventions, American College of Surgeons, and American Dental Association, with representation from the American College of Physicians. Circulation. 2007 ; 115 (6). 813-818. (Pubitemid 46294748)
136. Serebruany VL, Oshrine BR, Malinin AI, Atar D., Michelson AD, Ferguson JJ 3rd. Noncompliance in cardiovascular clinical trials. Am Heart J. 2005 ; 150 (5). 882-886. (Pubitemid 41607757)
137. Serebruany V., Cherala G., Williams C., et al. Association of platelet responsiveness with clopidogrel metabolism: role of compliance in the assessment of "resistance". Am Heart J. 2009 ; 158 (6). 925-932.