The evolution of antiplatelet therapy in cardiovascular disease

Nature Reviews Cardiology

Volumn 8, Issue 10, 2011, Pages 547-559

  Yousuf, Omair ^a   Bhatt, Deepak L ^b  

^a JOHNS HOPKINS UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b HARVARD MEDICAL SCHOOL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ABCIXIMAB; ACETYLSALICYLIC ACID; ACETYLSALICYLIC ACID 3 (NITROXYMETHYL)PHENYL ESTER; ANTITHROMBOCYTIC AGENT; ARACHIDONIC ACID; ARYLDIALKYLPHOSPHATASE 1; ATOPAXAR; CANGRELOR; CILOSTAZOL; CLOPIDOGREL; CYCLOOXYGENASE 1; CYTOCHROME P450 2C19; DIPYRIDAMOLE; ELINOGREL; EPTIFIBATIDE; FIBRINOLYTIC AGENT; GLYCOPROTEIN IIB/IIIA INHIBITOR; NONSTEROID ANTIINFLAMMATORY AGENT; OMEPRAZOLE; PLACEBO; PRASUGREL; PURINERGIC P2Y12 RECEPTOR; TEMANOGREL; TERUTROBAN; THROMBOXANE A2; TICAGRELOR; TICLOPIDINE; TIROFIBAN; TRIFLUSAL; UNCLASSIFIED DRUG; VORAPAXAR;

ACUTE CORONARY SYNDROME; ACUTE HEART INFARCTION; ARTICLE; ATHEROSCLEROSIS; BRADYCARDIA; BRAIN HEMORRHAGE; BRAIN ISCHEMIA; CARDIOVASCULAR DISEASE; COMPARATIVE STUDY; CORONARY ARTERY BYPASS GRAFT; CORONARY ARTERY DISEASE; CORONARY ARTERY THROMBOSIS; CREATININE CLEARANCE; DRUG EFFICACY; DRUG MECHANISM; DRUG METABOLISM; DYSPNEA; GASTROINTESTINAL SYMPTOM; HEART INFARCTION; HUMAN; LOADING DRUG DOSE; META ANALYSIS (TOPIC); NON ST SEGMENT ELEVATION MYOCARDIAL INFARCTION; PERCUTANEOUS CORONARY INTERVENTION; PRIMARY PREVENTION; PRIORITY JOURNAL; RISK REDUCTION; SECONDARY PREVENTION; SIDE EFFECT; ST SEGMENT ELEVATION MYOCARDIAL INFARCTION; STROKE; THROMBOCYTE ACTIVATION; THROMBOCYTE AGGREGATION;

BLOOD PLATELETS; CARDIOVASCULAR DISEASES; DRUG DESIGN; HEMORRHAGE; HUMANS; PATIENT SELECTION; PLATELET AGGREGATION INHIBITORS; RISK ASSESSMENT; TREATMENT OUTCOME;

EID: 80053289254     PISSN: 17595002     EISSN: 17595010     Source Type: Journal    
DOI: 10.1038/nrcardio.2011.96     Document Type: Article

References (145)

1. Chen, Z. M. et al. Addition of clopidogrel to aspirin in 45,852 patients with acute myocardial infarction: randomised placebo-controlled trial. Lancet 366, 1607-1621 (2005).
2. Sabatine, M. S. et al. Addition of clopidogrel to aspirin and fibrinolytic therapy for myocardial infarction with ST segment elevation. N. Engl. J. Med. 352, 1179-1189 (2005). (Pubitemid 40397259)
3. Yusuf, S. et al. Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST segment elevation. N. Engl. J. Med. 345, 494-502 (2001). (Pubitemid 32758501)
4. Mehta, S. R. & Yusuf, S. Short- and long-term oral antiplatelet therapy in acute coronary syndromes and percutaneous coronary intervention. J. Am. Coll. Cardiol. 41, 79S-88S (2003). (Pubitemid 36223351)
5. Mehta, S. R. 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 358, 527-533 (2001). (Pubitemid 32772726)
6. Steinhubl, S. R. et al. Early and sustained dual oral antiplatelet therapy following percutaneous coronary intervention: a randomized controlled trial. JAMA 288, 2411-2420 (2002). (Pubitemid 35340537)
7. Buonamici, P. et al. Impact of platelet reactivity after clopidogrel administration on drug-eluting stent thrombosis. J. Am. Coll. Cardiol. 49, 2312-2317 (2007). (Pubitemid 46891710)
8. Gurbel, P. A. et al. Clopidogrel effect on platelet reactivity in patients with stent thrombosis: results of the CREST Study. J. Am. Coll. Cardiol. 46, 1827-1832 (2005). (Pubitemid 41579803)
9. Hochholzer, W. et al. Impact of the degree of peri-interventional platelet inhibition after loading with clopidogrel on early clinical outcome of elective coronary stent placement. J. Am. Coll. Cardiol. 48, 1742-1750 (2006). (Pubitemid 44648629)
10. Matetzky, S. et al. Clopidogrel resistance is associated with increased risk of recurrent atherothrombotic events in patients with acute myocardial infarction. Circulation 109, 3171-3175 (2004).
11. Patti, G. et al. Point of care measurement of clopidogrel responsiveness predicts clinical outcome in patients undergoing percutaneous coronary intervention results of the ARMYDA-PRO (Antiplatelet therapy for Reduction of MYocardial Damage during Angioplasty-Platelet Reactivity Predicts Outcome) study. J. Am. Coll. Cardiol. 52, 1128-1133 (2008).
12. Sibbing, D. et al. Platelet reactivity after clopidogrel treatment assessed with point of care analysis and early drug-eluting stent thrombosis. J. Am. Coll. Cardiol. 53, 849-856 (2009).
13. Wallentin, L. et al. Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N. Engl. J. Med. 361, 1045-1057 (2009).
14. Wiviott, S. D. et al. Prasugrel versus clopidogrel in patients with acute coronary syndromes. N. Engl. J. Med. 357, 2001-2015 (2007). (Pubitemid 350106708)
15. Bhatt, D. L. Intensifying platelet inhibition-navigating between Scylla and Charybdis. N. Engl. J. Med. 357, 2078-2081 (2007). (Pubitemid 350106717)
16. ISIS 2 (Second International Study of Infarct Survival) Collaborative Group. Randomised trial of intravenous streptokinase, oral aspirin, both, or neither among 17,187 cases of suspected acute myocardial infarction. Lancet 2, 349-360 (1988).
17. Baigent, C. et al. ISIS 2: 10 year survival among patients with suspected acute myocardial infarction in randomised comparison of intravenous streptokinase, oral aspirin, both, or neither. The ISIS 2 (Second International Study of Infarct Survival) Collaborative Group. BMJ 316, 1337-1343 (1998). (Pubitemid 28195871)
18. 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 324, 71-86 (2002).
19. Bartolucci, A. A., Tendera, M. & Howard, G. Meta-analysis of multiple primary prevention trials of cardiovascular events using aspirin. Am. J. Cardiol. 107, 1796-1801 (2011).
20. Berger, J. S., Brown, D. L. & Becker, R. C. Low-dose aspirin in patients with stable cardiovascular disease: a meta-analysis. Am. J. Med. 121, 43-49 (2008).
21. Berger, J. S. et al. Aspirin use, dose, and clinical outcomes in postmenopausal women with stable cardiovascular disease: the Women's Health Initiative Observational Study. Circ. Cardiovasc. Qual. Outcomes 2, 78-87 (2009).
22. Steinhubl, S. R. et al. Aspirin to prevent cardiovascular disease: the association of aspirin dose and clopidogrel with thrombosis and bleeding. Ann. Intern. Med. 150, 379-386 (2009).
23. Jolly, S. S. et al. Effects of aspirin dose on ischaemic events and bleeding after percutaneous coronary intervention: insights from the PCI-CURE study. Eur. Heart J. 30, 900-907 (2009).
24. Joyal, D. et al. The influence of low (81 mg) versus high (325 mg) doses of ASA on the incidence of sirolimus-eluting stent thrombosis. J. Invasive Cardiol. 19, 291-294 (2007). (Pubitemid 47041848)
25. Peters, R. J. 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 108, 1682-1687 (2003). (Pubitemid 37243654)
26. Topol, E. J. et al. Randomized, double-blind, placebo-controlled, international trial of the oral IIb/IIIa antagonist lotrafiban in coronary and cerebrovascular disease. Circulation 108, 399-406 (2003). (Pubitemid 36935531)
27. Mehta, S. R. et al. Dose comparisons of clopidogrel and aspirin in acute coronary syndromes. N. Engl. J. Med. 363, 930-942 (2010).
28. Mehta, S. R. et al. Double-dose versus standard-dose clopidogrel and high-dose versus low-dose aspirin in individuals undergoing percutaneous coronary intervention for acute coronary syndromes (CURRENT-OASIS 7): a randomised factorial trial. Lancet 376, 1233-1243 (2010).
29. Hebert, P. R. & Hennekens, C. H. An overview of the 4 randomized trials of aspirin therapy in the primary prevention of vascular disease. Arch. Intern. Med. 160, 3123-3127 (2000).
30. De Berardis, G. et al. Aspirin for primary prevention of cardiovascular events in people with diabetes: meta-analysis of randomised controlled trials. BMJ 339, b4531 (2009).
31. Snoep, J. D., Hovens, M. M., Eikenboom, J. C., van der Bom, J. G. & Huisman, M. V. Association of laboratory-defined aspirin resistance with a higher risk of recurrent cardiovascular events: a systematic review and meta-analysis. Arch. Intern. Med. 167, 1593-1599 (2007). (Pubitemid 47280339)
32. Krasopoulos, G., Brister, S. J., Beattie, W. S. & Buchanan, M. R. Aspirin "resistance" and risk of cardiovascular morbidity: systematic review and meta-analysis. BMJ 336, 195-198 (2008). (Pubitemid 351212675)
33. Tantry, U. S., Bliden, K. P. & Gurbel, P. A. Overestimation of platelet aspirin resistance detection by thrombelastograph platelet mapping and validation by conventional aggregometry using arachidonic acid stimulation. J. Am. Coll. Cardiol. 46, 1705-1709 (2005). (Pubitemid 41531626)
34. Michelson, A. D. et al. Aspirin resistance: position paper of the Working Group on Aspirin Resistance. J. Thromb. Hemost. 3, 1309-1311 (2005). (Pubitemid 41725257)
35. Bhatt, D. L. Aspirin resistance: more than just a laboratory curiosity. J. Am. Coll. Cardiol. 43, 1127-1129 (2004). (Pubitemid 38353001)
36. Bhatt, D. L. et al. ACCF/ACG/AHA 2008 expert consensus document on reducing the gastrointestinal risks of antiplatelet therapy and NSAID use: a report of the American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents. J. Am. Coll. Cardiol. 52, 1502-1517 (2008).
37. Bhatt, D. L. NSAIDS and the risk of myocardial infarction: do they help or harm? Eur. Heart J. 27, 1635-1636 (2006). (Pubitemid 44025341)
38. Bhatt, D. L. Glycoprotein IIb/IIIa inhibitors: do they still have a role? J. Am. Coll. Cardiol. 57, 1200-1201 (2011).
39. Bhatt, D. L. & Topol, E. J. Current role of platelet glycoprotein IIb/IIIa inhibitors in acute coronary syndromes. JAMA 284, 1549-1558 (2000).
40. Boersma, E. et al. Platelet glycoprotein IIb/IIIa inhibitors in acute coronary syndromes: a meta-analysis of all major randomised clinical trials. Lancet 359, 189-198 (2002). (Pubitemid 34113814)
41. Chew, D. P., Bhatt, D. L., Sapp, S. & Topol, E. J. Increased mortality with oral platelet glycoprotein IIb/IIIa antagonists: a meta-analysis of phase III multicenter randomized trials. Circulation 103, 201-206 (2001). (Pubitemid 32095403)
42. Kastrati, A. et al. A clinical trial of abciximab in elective percutaneous coronary intervention after pretreatment with clopidogrel. N. Engl. J. Med. 350, 232-238 (2004). (Pubitemid 38071801)
43. Schömig, A. et al. One year outcomes with abciximab vs. placebo during percutaneous coronary intervention after pre-treatment with clopidogrel. Eur. Heart J. 26, 1379-1384 (2005). (Pubitemid 41373514)
44. Mehilli, J. et al. Randomized clinical trial of abciximab in diabetic patients undergoing elective percutaneous coronary interventions after treatment with a high loading dose of clopidogrel. Circulation 110, 3627-3635 (2004). (Pubitemid 40003783)
45. Kastrati, A. et al. Abciximab in patients with acute coronary syndromes undergoing percutaneous coronary intervention after clopidogrel pretreatment: the ISAR-REACT 2 randomized trial. JAMA 295, 1531-1538 (2006).
46. Deibele, A. J. et al. Intracoronary eptifibatide bolus administration during percutaneous coronary revascularization for acute coronary syndromes with evaluation of platelet glycoprotein IIb/IIIa receptor occupancy and platelet function: the Intracoronary Eptifibatide (ICE) Trial. Circulation 121, 784-791 (2010).
47. Boersma, E. et al. Platelet glycoprotein IIb/IIIa receptor inhibition in non ST elevation acute coronary syndromes: early benefit during medical treatment only, with additional protection during percutaneous coronary intervention. Circulation 100, 2045-2048 (1999). (Pubitemid 29532053)
48. Giugliano, R. P. et al. Early versus delayed, provisional eptifibatide in acute coronary syndromes. N. Engl. J. Med. 360, 2176-2190 (2009).
49. Stone, G. W. et al. Routine upstream initiation vs deferred selective use of glycoprotein IIb/IIIa inhibitors in acute coronary syndromes: the ACUITY Timing trial. JAMA 297, 591-602 (2007).
50. Stone, G. W. et al. Comparison of angioplasty with stenting, with or without abciximab, in acute myocardial infarction. N. Engl. J. Med. 346, 957-966 (2002). (Pubitemid 34983245)
51. De Luca, G. et al. Abciximab as adjunctive therapy to reperfusion in acute ST segment elevation myocardial infarction: a meta-analysis of randomized trials. JAMA 293, 1759-1765 (2005).
52. Mehilli, J. et al. Abciximab in patients with acute ST segment elevation myocardial infarction undergoing primary percutaneous coronary intervention after clopidogrel loading: a randomized double-blind trial. Circulation 119, 1933-1940 (2009).
53. Ellis, S. G. et al. Facilitated PCI in patients with ST elevation myocardial infarction. N. Engl. J. Med. 358, 2205-2217 (2008). (Pubitemid 351724450)
54. Lincoff, A. M. et al. Bivalirudin and provisional glycoprotein IIb/IIIa blockade compared with heparin and planned glycoprotein IIb/IIIa blockade during percutaneous coronary intervention: REPLACE 2 randomized trial. JAMA 289, 853-863 (2003). (Pubitemid 37430344)
55. Stone, G. W. et al. Bivalirudin during primary PCI in acute myocardial infarction. N. Engl. J. Med. 358, 2218-2230 (2008). (Pubitemid 351724451)
56. Stone, G. W. et al. Bivalirudin for patients with acute coronary syndromes. N. Engl. J. Med. 355, 2203-2216 (2006). (Pubitemid 44791162)
57. Scrutinio, D. et al. Ticlopidine versus aspirin after myocardial infarction (STAMI) trial. J. Am. Coll. Cardiol. 37, 1259-1265 (2001).
58. Balsano, F. et al. Antiplatelet treatment with ticlopidine in unstable angina. A controlled multicenter clinical trial. The Studio della Ticlopidina nell'Angina Instabile Group. Circulation 82, 17-26 (1990). (Pubitemid 20216311)
59. Hall, P. et al. A randomized comparison of combined ticlopidine and aspirin therapy versus aspirin therapy alone after successful intravascular ultrasound-guided stent implantation. Circulation 93, 215-222 (1996). (Pubitemid 26031477)
60. Urban, P. 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 98, 2126-2132 (1998). (Pubitemid 28527471)
61. Schömig, A. et al. A randomized comparison of antiplatelet and anticoagulant therapy after the placement of coronary-artery stents. N. Engl. J. Med. 334, 1084-1089 (1996). (Pubitemid 26120185)
62. Leon, M. B. et al. A clinical trial comparing three antithrombotic-drug regimens after coronary-artery stenting. Stent Anticoagulation Restenosis Study Investigators. N. Engl. J. Med. 339, 1665-1671 (1998). (Pubitemid 28550691)
63. Bertrand, M. E. 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 98, 1597-1603 (1998).
64. Bhatt, D. L. et al. Meta-analysis of randomized and registry comparisons of ticlopidine with clopidogrel after stenting. J. Am. Coll. Cardiol. 39, 9-14 (2002). (Pubitemid 34059855)
65. CAPRIE Steering Committee. A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). Lancet 348, 1329-1339 (1996).
66. Helton, T. J. et al. Incremental effect of clopidogrel on important outcomes in patients with cardiovascular disease: a meta-analysis of randomized trials. Am. J. Cardiovasc. Drugs 7, 289-297 (2007). (Pubitemid 47295838)
67. Bhatt, D. L. Can clopidogrel and aspirin lower mortality in patients with acute myocardial infarction? Nat. Clin. Pract. Cardiovasc. Med. 3, 182-183 (2006).
68. Bhatt, D. L. et al. Clopidogrel and aspirin versus aspirin alone for the prevention of atherothrombotic events. N. Engl. J. Med. 354, 1706-1717 (2006).
69. Bhatt, D. L. et al. Patients with prior myocardial infarction, stroke, or symptomatic peripheral arterial disease in the CHARISMA trial. J. Am. Coll. Cardiol. 49, 1982-1988 (2007). (Pubitemid 46694290)
70. Wang, T. H. et al. An analysis of mortality rates with dual-antiplatelet therapy in the primary prevention population of the CHARISMA trial. Eur. Heart J. 28, 2200-2207 (2007). (Pubitemid 47428941)
71. von Beckerath, N. et al. 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 112, 2946-2950 (2005). (Pubitemid 41612296)
72. Montalescot, G. 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. 48, 931-938 (2006). (Pubitemid 44292463)
73. Patti, G. et al. 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 111, 2099-2106 (2005). (Pubitemid 40577905)
74. Cuisset, T. et al. Benefit of a 600 mg loading dose of clopidogrel on platelet reactivity andclinical outcomes in patients with non ST segment elevation acute coronary syndrome undergoing coronary stenting. J. Am. Coll. Cardiol. 48, 1339-1345 (2006). (Pubitemid 44436814)
75. von Beckerath, N. 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. 28, 1814-1819 (2007). (Pubitemid 47236637)
76. Patti, G. et al. High versus standard clopidogrel maintenance dose after percutaneous coronary intervention and effects on platelet inhibition, endothelial function, and inflammation results of the ARMYDA 150 mg (Antiplatelet Therapy for Reduction of Myocardial Damage During Angioplasty) randomized study. J. Am. Coll. Cardiol. 57, 771-778 (2011).
77. Bonello, L. 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. 51, 1404-1411 (2008). (Pubitemid 351447314)
78. Price, M. J. Standard versus high-dose clopidogrel according to platelet function testing after PCI: results of the GRAVITAS trial [abstract 21791]. 2010 Clinical Trial/Clinical Science Abstracts. Circulation 122, 2215-2226 (2010).
79. Collet, J. P. et al. Randomized comparison of platelet function monitoring to adjust antiplatelet therapy versus standard of care: rationale and design of the assessment with a double randomization of (1) a fixed dose versus a monitoring-guided dose of aspirin and clopidogrel after DES implantation, and (2) treatment interruption versus continuation, 1 year after stenting (ARCTIC) study. Am. Heart J. 161, 5e5-12e5 (2011).
80. Bhatt, D. L. Tailoring antiplatelet therapy based on pharmacogenomics: how well do the data fit? JAMA 302, 896-897 (2009).
81. Sabatine, M. S. 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 294, 1224-1232 (2005). (Pubitemid 41352110)
82. Bavry, A. A. & Bhatt, D. L. Appropriate use of drug-eluting stents: balancing the reduction in restenosis with the concern of late thrombosis. Lancet 371, 2134-2143 (2008). (Pubitemid 351842583)
83. Kushner, F. G. et al. 2009 focused updates: ACC/AHA guidelines for the management of patients with ST elevation myocardial infarction (updating the 2004 guideline and 2007 focused update) and ACC/AHA/SCAI guidelines on percutaneous coronary intervention (updating the 2005 guideline and 2007 focused update) a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J. Am. Coll. Cardiol. 54, 2205-2241 (2009).
84. Desai, N. R. & Bhatt, D. L. The state of periprocedural antiplatelet therapy after recent trials. JACC Cardiovasc. Interv. 3, 571-583 (2010).
85. Gurbel, P. A., Bliden, K. P., Hiatt, B. L. & O'Connor, C. M. Clopidogrel for coronary stenting: response variability, drug resistance, and the effect of pretreatment platelet reactivity. Circulation 107, 2908-2913 (2003). (Pubitemid 36736631)
86. Müller, I. et al. Prevalence of clopidogrel non-responders among patients with stable angina pectoris scheduled for elective coronary stent placement. Thromb. Hemost. 89, 783-787 (2003). (Pubitemid 36603418)
87. Serebruany, V. L. et al. Variability in platelet responsiveness to clopidogrel among 544 individuals. J. Am. Coll. Cardiol. 45, 246-251 (2005). (Pubitemid 40094733)
88. Gurbel, P. A. 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 111, 1153-1159 (2005). (Pubitemid 40365477)
89. Lev, E. I. et al. Aspirin and clopidogrel drug response in patients undergoing percutaneous coronary intervention: the role of dual drug resistance. J. Am. Coll. Cardiol. 47, 27-33 (2006). (Pubitemid 43005160)
90. Bhatt, D. L. What makes platelets angry: diabetes, fibrinogen, obesity, and impaired response to antiplatelet therapy? J. Am. Coll. Cardiol. 52, 1060-1061 (2008).
91. Bhatt, D. L. Resisting the temptation to oversimplify antiplatelet resistance. JACC Cardiovasc. Interv. 1, 660-662 (2008).
92. Breet, N. J. et al. Comparison of platelet function tests in predicting clinical outcome in patients undergoing coronary stent implantation. JAMA 303, 754-762 (2010).
93. Cuisset, T. et al. Predictive value of post-treatment platelet reactivity for occurrence of post-discharge bleeding after non-ST elevation acute coronary syndrome. Shifting from antiplatelet resistance to bleeding risk assessment? EuroIntervention 5, 325-329 (2009).
94. Shuldiner, A. R. et al. Association of cytochrome P450 2C19 genotype with the antiplatelet effect and clinical efficacy of clopidogrel therapy. JAMA 302, 849-857 (2009).
95. Mega, J. L. et al. Cytochrome p 450 polymorphisms and response to clopidogrel. N. Engl. J. Med. 360, 354-362 (2009).
96. Mega, J. L. 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 376, 1312-1319 (2010).
97. Mega, J. L. et al. Reduced-function CYP2C19 genotype and risk of adverse clinical outcomes among patients treated with clopidogrel predominantly for PCI: a meta-analysis. JAMA 304, 1821-1830 (2010).
98. Pare, G. et al. Effects of CYP2C19 genotype on outcomes of clopidogrel treatment. N. Engl. J. Med. 363, 1704-1714 (2010).
99. Bouman, H. J. et al. Paraoxonase 1 is a major determinant of clopidogrel efficacy. Nat. Med. 17, 110-116 (2011).
100. Bhatt, D. L. Tailoring antiplatelet therapy based on pharmacogenomics: how well do the data fit? JAMA 302, 896-897 (2009).
101. Bhatt, D. L. et al. Clopidogrel with or without omeprazole in coronary artery disease. N. Engl. J. Med. 363, 1909-1917 (2010).
102. Abraham, N. S. et al. ACCF/ACG/AHA 2010 Expert Consensus Document on the concomitant use of proton pump inhibitors and thienopyridines: a focused update of the ACCF/ACG/AHA 2008 expert consensus document on reducing the gastrointestinal risks of antiplatelet therapy and NSAID use: a report of the American College of Cardiology Foundation Task Force on Expert Consensus Documents. Circulation 122, 2619-2633 (2010).
103. Olesen, J. B. et al. Calcium-channel blockers do not alter the clinical efficacy of clopidogrel after myocardial infarction a nationwide cohort study. J. Am. Coll. Cardiol. 57, 409-417 (2011).
104. Serebruany, V. L. et al. Absence of interaction between atorvastatin or other statins and clopidogrel: results from the interaction study. Arch. Intern. Med. 164, 2051-2057 (2004). (Pubitemid 39390564)
105. Wallentin, L. et al. Effect of CYP2C19 and ABCB1 single nucleotide polymorphisms on outcomes of treatment with ticagrelor versus clopidogrel for acute coronary syndromes: a genetic substudy of the PLATO trial. Lancet 376, 1320-1328 (2010).
106. Wiviott, S. D. et al. Prasugrel compared with high loading- and maintenance-dose clopidogrel in patients with planned percutaneous coronary intervention: the Prasugrel in Comparison to Clopidogrel for Inhibition of Platelet Activation and Aggregation-Thrombolysis in Myocardial Infarction 44 trial. Circulation 116, 2923-2932 (2007). (Pubitemid 350291199)
107. Wiviott, S. D. et al. Intensive oral antiplatelet therapy for reduction of ischaemic events including stent thrombosis in patients with acute coronary syndromes treated with percutaneous coronary intervention and stenting in the TRITON-TIMI 38 trial: a subanalysis of a randomised trial. Lancet 371, 1353-1363 (2008).
108. Montalescot, G. et al. Prasugrel compared with clopidogrel in patients undergoing percutaneous coronary intervention for ST elevation myocardial infarction (TRITON-TIMI 38): double-blind, randomised controlled trial. Lancet 373, 723-731 (2009).
109. Wiviott, S. D. 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 118, 1626-1636 (2008).
110. Bhatt, D. L. Prasugrel in clinical practice. N. Engl. J. Med. 361, 940-942 (2009).
111. US NIH. ClinicalTrials.gov. A Comparison of Prasugrel and Clopidogrel in Acute Coronary Syndrome Subjects (TRILOGY ACS) [online], http://clinicaltrials. gov/ct2/show/NCT00699998 (2011).
112. Bhatt, D. L. Is prasugrel superior to clopidogrel for patients with acute coronary syndromes undergoing PCI? Nat. Clin. Pract. Cardiovasc. Med. 5, 252-253 (2008). (Pubitemid 351593906)
113. Angiolillo, D. J. et al. Increased platelet inhibition after switching from maintenance clopidogrel to prasugrel in patients with acute coronary syndromes: results of the SWAP (SWitching Anti Platelet) study. J. Am. Coll. Cardiol. 56, 1017-1023 (2010).
114. Cannon, C. P. 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 375, 283-293 (2010).
115. Held, C. et al. Ticagrelor versus clopidogrel in patients with acute coronary syndromes undergoing coronary artery bypass surgery results from the PLATO (Platelet Inhibition and Patient Outcomes) trial. J. Am. Coll. Cardiol. 57, 672-684 (2010).
116. Steg, P. G. et al. Ticagrelor versus clopidogrel in patients with ST elevation acute coronary syndromes intended for reperfusion with primary percutaneous coronary intervention: A Platelet Inhibition and Patient Outcomes (PLATO) trial subgroup analysis. Circulation 122, 2131-2141 (2010).
117. Bhatt, D. L. Antiplatelet therapy: Ticagrelor in ACS-what does PLATO teach us? Nat. Rev. Cardiol. 6, 737-738 (2009).
118. Schneider, D. J. Mechanisms potentially contributing to the reduction in mortality associated with ticagrelor therapy. J. Am. Coll. Cardiol. 57, 685-687 (2011).
119. Cuisset, T. et al. Comparison of omeprazole and pantoprazole influence on a high 150 mg clopidogrel maintenance dose the PACA (Proton Pump Inhibitors And Clopidogrel Association) prospective randomized study. J. Am. Coll. Cardiol. 54, 1149-1153 (2009).
120. Tantry, U. S. et al. First analysis of the relation between CYP2C19 genotype and pharmacodynamics in patients treated with ticagrelor versus clopidogrel: the ONSET/OFFSET and RESPOND genotype studies. Circ. Cardiovasc. Genet. 3, 556-566 (2010).
121. Gurbel, P. A. et al. Response to ticagrelor in clopidogrel nonresponders and responders and effect of switching therapies: the RESPOND study. Circulation 121, 1188-1199 (2010).
122. US Department of Health and Human Services. Ticagrelor for acute coronary syndromes, NDA 22-433 [online], http://www.fda.gov/downloads/ AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/ CardiovascularandRenalDrugsAdvisoryCommittee/UCM220192pdf (2010).
123. US NIH. ClinicalTrials.gov. Prevention of Cardiovascular Events (eg, Death From Heart or Vascular Disease, Heart Attack, or Stroke) in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin (PEGASUS) [online], http://clinicaltrials.gov/ct2/show/NCT01225562 (2011).
124. Harrington, R. A. et al. Platelet inhibition with cangrelor in patients underoing PCI. N. Engl. J. Med. 361, 2318-2329 (2009).
125. Bhatt, D. L. et al. Intravenous platelet blockade with cangrelor during PCI. N. Engl. J. Med. 361, 2330-2341 (2009).
126. US NIH. ClinicalTrials.gov. A Clinical Trial Comparing Cangrelor to Clopidogrel Standard Therapy in Subjects Who Require Percutaneous Coronary Intervention (CHAMPION PHOENIX) [online], http://clinicaltrials.gov/ct2/show/ NCT01156571 (2010).
127. Leonardi, S. et al. Rationale and design of the randomized, double-blind trial testing INtraveNous and Oral administration of elinogrel, a selective and reversible P2Y(12)-receptor inhibitor, versus clopidogrel to eVAluate Tolerability and Efficacy in nonurgent Percutaneous Coronary Interventions patients (INNOVATE-PCI). Am. Heart J. 160, 65-72 (2010).
128. Rao, S. V. INNOVATE-PCI: a phase II safety and efficacy study of PRT060128 (elinogrel), a novel intravenous and oral P2Y12 inhibitor, in non-urgent PCI [abstract 2036]. Presented at the 2010 ESC Congress.
129. Gurbel, P. A. et al. Randomized double-blind assessment of the ONSET and OFFSET of the antiplatelet effects of ticagrelor versus clopidogrel in patients with stable coronary artery disease: the ONSET/OFFSET study. Circulation 120, 2577-2585 (2009).
130. Jeong, Y. H. et al. Adding cilostazol to dual antiplatelet therapy achieves greater platelet inhibition than high maintenance dose clopidogrel in patients with acute myocardial infarction: Results of the adjunctive cilostazol versus high maintenance dose clopidogrel in patients with AMI (ACCEL-AMI) study. Circ. Cardiovasc. Interv. 3, 17-6 (2010).
131. Tamhane, U. et al. Efficacy of cilostazol in reducing restenosis in patients undergoing contemporary stent based PCI: a meta-analysis of randomised controlled trials. EuroIntervention 5, 384-393 (2009).
132. Kumbhani, D. J. & Bhatt, D. L. Secondary prevention of stroke: can we do better than aspirin? Lancet Neurol. 9, 942-943 (2010).
133. Suh, J. W. et al. Multicenter randomized trial evaluating the efficacy of cilostazol on ischemic vascular complications after drug-eluting stent implantation for coronary heart disease: results of the CILON T (influence of CILostazol-based triple antiplatelet therapy ON ischemic complication after drug-eluting stenT implantation) trial. J. Am. Coll. Cardiol. 57, 280-289 (2011).
134. Verro, P., Gorelick, P. B. & Nguyen, D. Aspirin plus dipyridamole versus aspirin for prevention of vascular events after stroke or TIA: a meta-analysis. Stroke 39, 1358-1363 (2008). (Pubitemid 351440719)
135. Diener, H. C. et al. Aspirin and clopidogrel compared with clopidogrel alone after recent ischaemic stroke or transient ischaemic attack in high-risk patients (MATCH): randomised, double-blind, placebo-controlled trial. Lancet 364, 331-337 (2004).
136. Sacco, R. L. et al. Aspirin and extended-release dipyridamole versus clopidogrel for recurrent stroke. N. Engl. J. Med. 359, 1238-1251 (2008).
137. Costa, J., Ferro, J. M., Matias-Guiu, J., Alvarez Sabin, J. & Torres, F. Triflusal for preventing serious vascular events in people at high risk. Cochrane Database of Systematic Reviews Issue 3 Art. No.: CD004296 doi:101002/14651858CD004296pub2 (2005).
138. US NIH. ClinicalTrials.gov. CoMparison of TriflusAl and Clopidogrel Effect in Secondary Prevention of STroke Based on the CytochRome P450 2C19 GenOtyping (MAESTRO) [online], http://clinicaltrials.gov/ct2/show/NCT01174693 (2011).
139. US NIH. ClinicalTrials.gov. Trial to Assess the Effects of SCH 530348 in Preventing Heart Attack and Stroke in Patients With Acute Coronary Syndrome (TRACER) [online], http://clinicaltrials.gov/ct2/show/NCT00527943 (2011).
140. US NIH. ClinicalTrials.gov. Trial to Assess the Effects of SCH 530348 in Preventing Heart Attack and Stroke in Patients With Atherosclerosis (TRA 2°P-TIMI 50) [online], http://clinicaltrials.gov/ct2/show/NCT00526474 (2010).
141. Goto, S., Ogawa, H., Takeuchi, M., Flather, M. D. & Bhatt, D. L. for the J LANCELOT Investigators. Double-blind, placebo-controlled Phase II studies of the protease-activated receptor 1 antagonist E5555 (atopaxar) in Japanese patients with acute coronary syndrome or high-risk coronary artery disease. Eur. Heart J. 31, 2601-2613 (2010).
142. O'Donoghue, M. L. et al. Safety and tolerability of atopaxar in the treatment of patients with acute coronary syndromes: the Lessons From Antagonizing the Cellular Effects of Thrombin-Acute Coronary Syndromes Trial. Circulation 123, 1843-1853 (2011).
143. Wiviott, S. D. et al. Randomized trial of atopaxar in the treatment of patients with coronary artery disease: the Lessons From Antagonizing the Cellular Effect of Thrombin-Coronary Artery Disease Trial. Circulation 123, 1854-1863 (2011).
144. Michelson, A. D. Antiplatelet therapies for the treatment of cardiovascular disease. Nat. Rev. Drug Discov. 9, 154-169 (2010).
145. Bousser, M. G. et al. Terutroban versus aspirin in patients with cerebral ischaemic events (PERFORM): a randomised, double-blind, parallel-group trial. Lancet 377, 2013-2022 (2011).