Ticagrelor: A review of its use in the management of acute coronary syndromes

Drugs

Volumn 71, Issue 7, 2011, Pages 909-933

  Deeks, Emma D ^a  

^a ADIS INTERNATIONAL LIMITED   (New Zealand)

Author keywords

Acute coronary syndromes; Adis Drug Evaluations; Ticagrelor

Indexed keywords

ACETYLSALICYLIC ACID; AMPRENAVIR; APREPITANT; ARC 124910XX; ATAZANAVIR; ATORVASTATIN; CARBAMAZEPINE; CLARITHROMYCIN; CLOPIDOGREL; DEXAMETHASONE; DILTIAZEM; ERYTHROMYCIN; ETHINYLESTRADIOL; FLUCONAZOLE; KETOCONAZOLE; MEVINOLIN; NEFAZODONE; PHENOBARBITAL; PHENYTOIN; PLACEBO; PRASUGREL; PURINERGIC P2Y12 RECEPTOR; QUINIDINE; RIFAMPICIN; RITONAVIR; SIMVASTATIN; TICAGRELOR; TOLBUTAMIDE; UNCLASSIFIED DRUG; UNINDEXED DRUG; VERAPAMIL; WARFARIN;

ACUTE CORONARY SYNDROME; ANTICOAGULATION; AREA UNDER THE CURVE; ARTICLE; ATHEROSCLEROSIS; BLEEDING; BLOOD CLOTTING; BRADYCARDIA; BRAIN HEMORRHAGE; CLINICAL TRIAL; CORONARY ARTERY BYPASS GRAFT; CORONARY ARTERY DISEASE; DATA BASE; DISEASE ASSOCIATION; DRUG ABSORPTION; DRUG BIOAVAILABILITY; DRUG DISTRIBUTION; DRUG EFFECT; DRUG EFFICACY; DRUG ELIMINATION; DRUG HALF LIFE; DRUG INDICATION; DRUG INTERACTION; DRUG MECHANISM; DRUG METABOLISM; DRUG RECEPTOR BINDING; DRUG TOLERABILITY; DYSPNEA; ENZYME INHIBITION; EPISTAXIS; FOOD; FOOD DRUG INTERACTION; GASTROINTESTINAL HEMORRHAGE; GENOTYPE; HEART BLOCK; HEART DEATH; HEART INFARCTION; HEART MUSCLE ISCHEMIA; HUMAN; HYPERURICEMIA; INJECTION SITE BLEEDING; LOADING DRUG DOSE; MAXIMUM PLASMA CONCENTRATION; NON ST SEGMENT ELEVATION MYOCARDIAL INFARCTION; NONHUMAN; PERCUTANEOUS CORONARY INTERVENTION; QT INTERVAL; SKIN BLEEDING; SKIN BRUISING; ST SEGMENT ELEVATION MYOCARDIAL INFARCTION; STROKE; SUBCUTANEOUS HEMORRHAGE; SYNCOPE; THROMBOCYTE AGGREGATION; THROMBOCYTE FUNCTION; TREATMENT DURATION; TREATMENT RESPONSE; UNSTABLE ANGINA PECTORIS; VENTRICULAR PAUSE;

ACUTE CORONARY SYNDROME; ADENOSINE; ANIMALS; HUMANS; MULTICENTER STUDIES AS TOPIC; PURINERGIC P2Y RECEPTOR ANTAGONISTS; RANDOMIZED CONTROLLED TRIALS AS TOPIC;

ANGINA;

EID: 79956225628     PISSN: 00126667     EISSN: 11791950     Source Type: Journal    
DOI: 10.2165/11206850-000000000-00000     Document Type: Article

References (82)

1. American Heart Association. Acute coronary syndrome [online]. Available from URL: http://www.americanheart. org/presenter.jhtml?identifier=3010002 [Accessed 2011 Jan 19].
2. Bassand JP, Hamm CW, Ardissino D, et al. Guidelines for the diagnosis and treatment of non-ST-segment elevation acute coronary syndromes. Eur Heart J 2007 Jul; 28 (13): 1598-1660.
3. American Heart Association. Atherosclerosis [online]. Available from URL: http://www.americanheart.org/pre senter.jhtml?identifier=4440 [Accessed 2011 Mar 22].
4. Chhabra N. Endothelial dysfunction: a predictor of atherosclerosis. Internet J Med Update 2009 Jan; 4 (1): 33-41.
5. Gharacholou SM, Lopes RD, Washam JB, et al. Antithrombotic therapy in acute coronary syndromes: guidelines translated for the clinician. J Thrombosis Thrombolysis 2010 May; 29 (4): 516-528.
6. Steinhubl SR, Moliterno DJ. The role of the platelet in the pathogenesis of atherothrombosis.Am J Cardiovasc Drugs 2005; 5 (6): 399-408. (Pubitemid 41584840)
7. Davi G, Patrono C. Platelet activation and atherothrombosis. N Engl J Med 2007 Dec 13; 357 (24): 2482-2494.
8. Angiolillo DJ. ADP receptor antagonism: what's in the pipeline? Am J Cardiovasc Drugs 2007; 7 (6): 423-432. (Pubitemid 350256050)
9. Capodanno D, Dharmashankar K, Angiolillo DJ. Mechanism of action and clinical development of ticagrelor, a novel platelet ADP P2Y12 receptor antagonist. Expert Rev Cardiovasc Ther 2010 Feb; 8 (2): 151-158.
10. Dib C,Hanna EB, Abu-Fadel MS.A new era for antiplatelet therapy in patients with acute coronary syndrome. Am J Med Sci 2010 Nov; 340 (5): 407-411.
11. Kowalczyk M, Banach M, Mikhailidis DP, et al. Ticagrelor: a new platelet aggregation inhibitor in patients with acute coronary syndromes. An improvement of other inhibitors? Med Sci Monit 2009 Dec; 15 (12): MS24-30.
12. Plosker GL, Lyseng-Williamson KA. Clopidogrel: a review of its use in the prevention of thrombosis. Drugs 2007; 67 (4): 613-646. (Pubitemid 46442637)
13. Tapp L, Shantsila E, Lip GYH. Role of ticagrelor in clopidogrel nonresponders: resistance is futile? Circulation 2010 Mar 16; 121 (10): 1169-1171.
14. Iyú D, Glenn JR, White AE, et al. Mode of action of P2Y12 antagonists as inhibitors of platelet function. Thromb Haemost 2011 Jan 3; 105 (1): 96-106.
15. Hö gberg C, Svensson H, Gustafsson R. The reversible oral P2Y12 antagonist AZD6140 inhibits ADP-induced contractions in murine and human vasculature. Int J Cardiol 2010 Jul 9; 142 (2): 187-192.
16. Patil SB, Jackman LE, Francis SE, et al. Ticagrelor effectively and reversibly blocks murine platelet P2Y12-mediated thrombosis and demonstrates a requirement for sustained P2Y12 inhibition to prevent subsequent neointima. Arterioscler Thromb Vasc Biol 2010 Dec; 30 (12): 2385-2391.
17. Wang K, Zhou X, Huang Y, et al. Adjunctive treatment with ticagrelor, but not clopidogrel, added to tPA enables sustained coronary artery recanalisation with recovery of myocardium perfusion in a canine coronary thrombosis model. Thromb Haemost 2010 Sep; 104 (3): 609-617.
18. van Giezen JJJ, Berntsson P, Zachrisson H, et al. Comparison of ticagrelor and thienopyridine P2Y12 binding characteristics and antithrombotic and bleeding effects in rat and dog models of thrombosis/hemostasis. Thromb Res 2009 Nov; 124 (5): 565-571.
19. van Giezen JJJ, Nilsson L, Berntsson P, et al. Ticagrelor binds to human P2Y12 independently from ADP but antagonizes ADP-induced receptor signaling and platelet aggregation. J Thromb Haemost 2009 Sep; 7 (9): 1556-1565.
20. Bjö rkman JA, Kirk I, van Giezen JJ. AZD6140 inhibits adenosine uptake into erythrocytes and enhances coronary blood flow after local ischemia or intracoronary adenosine infusion [abstract no. 245]. Circulation 2007; 116 (16 Suppl.): 11-28.
21. Husted S, Emanuelsson H, Heptinstall S, et al. 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 May; 27 (9): 1038-1047.
22. Gurbel PA, Bliden KP, Butler K, et al. Response to ticagrelor in clopidogrel nonresponders and responders and effect of switching therapies. The RESPOND study. Circulation 2010 Mar 16; 121 (10): 1188-1199.
23. Gurbel PA, Bliden KP, Butler K, et al. Randomized doubleblind 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 2009 Dec 22; 120 (25): 2577-2585.
24. Storey RF, Bliden KP, Patil SB, et al. Incidence of dyspnea and assessment of cardiac and pulmonary function in patients with stable coronary artery disease receiving ticagrelor, clopidogrel, or placebo in the ONSET/OFFSET study. J Am Coll Cardiol 2010 Jul 13; 56 (3): 185-193.
25. Tantry US, Bliden KP, Wei C, 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 2010 Dec 1; 3 (6): 556-566.
26. Storey RF, Bliden KP, Patil SB, et al. Earlier recovery of platelet function after treatment cessation in ticagrelortreated patients compared to clopidogrel high responders [abstract no. P2313]. EurHeart J 2010 Sep; 31 Suppl. 1: 389.
27. Bliden K, Tantry U, Antonino M, et al. Differential effect of ticagrelor versus clopidogrel on the prevalence of high ontreatment platelet reactivity: results from the ONSETOFFSET study [abstract no. 5900]. Circulation 2009; 120: S1172-1173.
28. Storey RF, Thornton SM, Lawrance R, et al. Ticagrelor yields consistent dose-dependent inhibition of ADPinduced platelet aggregation in patients with atherosclerotic disease regardless of genotypic variations in P2RY12, P2RY1, and ITGB3. Platelets 2009 Aug; 20 (5): 341-348.
29. Husted S, Storey RF, Harrington RA, et al. Changes in inflammatory biomarkers in patients treated with ticagrelor or clopidogrel. Clin Cardiol 2010 Apr; 33 (4): 206-212.
30. 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 Nov 6; 50 (19): 1852-1856. (Pubitemid 350017792)
31. Patil SB, Angiolillo DJ, Desai B, et al. Platelet inhibition by ticagrelor is not affected by proton pump inhibitors: results from the PLATO platelet substudy [abstract no. 5067]. Eur Heart J 2010 Sep; 31 Suppl. 1: 905-906.
32. Storey RF, Becker RC, Cannon CP, et al. Ticagrelor does not affect pulmonary function tests compared to clopidogrel in acute coronary syndromes: results of the PLATO pulmonary substudy [abstract no. 1100-276]. J Am Coll Cardiol 2010 Mar 9; 55 (10A).
33. Storey RF, Angiolillo DJ, Patil SB, et al. Inhibitory effects of ticagrelor compared with clopidogrel on platelet function in patients with acute coronary syndromes. The PLATO (PLATelet inhibition and patient Outcomes) platelet substudy. J Am Coll Cardiol 2010 Oct 26; 56 (18): 1456-1462.
34. Wallentin L, Becker RC, Budaj A, et al. Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med 2009 Sep 10; 361 (11): 1045-1057.
35. 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 [published erratum appears in J Am Coll Cardiol 2007 Nov 27; 50 (22): 2196]. J Am Coll Cardiol 2007 Nov 6; 50 (19): 1844-1851. (Pubitemid 350007959)
36. Butler K, Wei C, Teng R. Single-dose ticagrelor does not prolong the QT interval in healthy subjects. Int J Clin Pharmacol Ther 2010 Oct; 48 (10): 643-651.
37. Teng R, Butler K. Pharmacokinetics, pharmacodynamics, tolerability and safety of single ascending doses of ticagrelor, a reversibly binding oral P2Y12 receptor antagonist, in healthy subjects. Eur J Clin Pharmacol 2010 May; 66 (5): 487-496.
38. Butler K, Teng R. Pharmacokinetics, pharmacodynamics, safety and tolerability of multiple ascending doses of ticagrelor in healthy volunteers. Br J Clin Pharmacol 2010 Jul; 70 (1): 65-77.
39. AstraZeneca UK Limited. Brilique 90 mg film coated tablets: UK summary of product characteristics [online]. Available from URL: http://www.medicines.org. uk/EMC/ medicine/23935/SPC/Brilique+90+mg+film+coated+tablets/ [Accessed 2011 Apr 6].
40. AstraZeneca AB. Brilique 90mg film-coated tablets: EU summary of product characteristics [online]. Available from URL: http://www.ema.europa.eu/docs/en- GB/docu ment-library/EPAR-Product-Information/human/001241/ WC500100494.pdf [Accessed 2011 Apr 6].
41. European Medicines Agency. Assessment report for Brilique [online]. Available from URL: http://www.ema.europa.eu/ docs/en-GB/document-library/EPAR- Publicassessment- report/human/001241/WC500100492.pdf [Accessed 2011 Apr 6].
42. Frelinger AL, Michelson AD. Clopidogrel. Linking evaluation of platelet response variability to mechanismof action. J Am Coll Cardiol 2005 Aug 16; 46 (4): 646-647. (Pubitemid 41132691)
43. Labarthe B, Thé roux P, Angioi . M, et al. Matching the evaluation of the clinical efficacy of clopidogrel to platelet function tests relevant to the biological properties of the drug. J Am Coll Cardiol 2005 Aug 16; 46 (4): 638-645. (Pubitemid 41132690)
44. Springthorpe B, Bailey A, Barton P, et al. From ATP to AZD6140: the discovery of an orally active reversible P2Y12 receptor antagonist for the prevention of thrombosis. Bioorg Med Chem Lett 2007 Nov 1; 17 (21): 6013-6018. (Pubitemid 47446193)
45. Husted S, van Giezen JJJ. Ticagrelor: the first reversibly binding oral P2Y12 receptor antagonist. Cardiovasc Ther 2009 Winter; 27 (4): 259-274.
46. Lucas AR, Korol R, Pepine CJ. Inflammation in atherosclerosis. Some thoughts about acute coronary syndromes. Circulation 2006 May 2; 113 (17): e728-732.
47. Husted SE, Gurbel P, Storey RF, et al. Pharmacokinetics and pharmacodynamics of ticagrelor in patients with stable coronary artery disease [abstract no. 5494]. Circulation 2009 Nov; 120 (18 Suppl.): S1102.
48. Teng R, Oliver S, Hayes MA, et al. Absorption, distribution, metabolism, and excretion of ticagrelor in healthy subjects. Drug Metab Dispos 2010 Sep; 38 (9): 1514-1521.
49. Ruckle JL, Winter HR, Garber S, et al. Single-dose pharmacokinetics, pharmacodynamics, and tolerability of the reversible oral ADP P2Y12 receptor antagonist AZD6140 are similar for healthy Japanese and Caucasian volunteers [abstract no. PII-4]. Clin Pharmacol Ther 2007 Mar; 81 Suppl. 1: S49.
50. Butler K, Mitchell PD, Teng R. No significant food effect on the pharmacokinetics of AZD6140, the first reversible oral P2Y12 receptor antagonist, in healthy subjects [abstract no. PI-39]. Clin Pharmacol Ther 2009; 85 Suppl. 1: S20.
51. Zhou D, Andersson TB, Grimm SW. In vitro evaluation of potential drug-drug interactions with ticagrelor: cytochrome P450 reaction phenotyping, inhibition, induction, and differential kinetics. Drug Metab Dispos 2011 Apr; 39 (4): 703-710.
52. James S, Akerblom A, Cannon CP, et al. Comparison of ticagrelor, the first reversible oral P2Y12 receptor antagonist, with clopidogrel in patients with acute coronary syndromes: rationale, design, and baseline characteristics of the PLATelet inhibition and patient Outcomes (PLATO) trial. Am Heart J 2009 Apr; 157 (4): 599-605.
53. James S, Budaj A, Aylward P, et al. Ticagrelor versus clopidogrel in acute coronary syndromes in relation to renal function. Results from the PLATelet inhibition and patient Outcomes (PLATO) trial. Circulation 2010 Sep 14; 122 (11): 1056-1067.
54. 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 Jan 23; 375 (9711): 283-293.
55. Held C, A ? senblad N, Bassand JP, 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 2011 Feb 8; 57 (6): 672-684.
56. Wallentin L, James S, Storey RF, 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 2010 Oct 16; 376 (9749): 1320-1328.
57. James S, Angiolillo DJ, Cornel JH, et al. Ticagrelor vs. clopidogrel in patients with acute coronary syndromes and diabetes: a substudy fromthe PLATelet inhibition and patient Outcomes (PLATO) trial. Eur Heart J 2010 Dec; 31 (24): 3006-3016.
58. Steg PG, James S, Harrington RA, et al. Ticagrelor versus clopidogrel in patients with ST-elevation acute coronary syndromes intended for reperfusion with primary percuta- neous coronary intervention. A PLATelet inhibition and patient Outcomes (PLATO) trial subgroup analysis. Circulation 2010 Nov 23; 122 (21): 2131-2141.
59. Storey RF, Becker RC, Harrington RA, et al. Increased incidence of dyspnoea associated with ticagrelor did not appear to adversely affect cardiovascular outcomes in the PLATO study [abstract no. P1352]. Eur Heart J 2010 Sep; 31 Suppl. 1: 203.
60. Van de Werf F, Bax J, Betriu A, et al. Management of acute myocardial infarction in patients presenting with persistent ST-segment elevation. The Task Force on the management of ST-segment elevation acute myocardial infarction of the European Society of Cardiology. Eur Heart J 2008 Dec; 29 (23): 2909-2945.
61. Ramanath VS, Eagle KA. Evidence-based medical therapy of patients with acute coronary syndromes. Am J Cardiovasc Drugs 2007; 7 (2): 95-116. (Pubitemid 46790266)
62. Fuster V, Sweeny JM. Clopidogrel and the reduced-function CYP2C19 genetic variant. JAMA 2010 Oct 27; 304 (16): 1839-1840.
63. Abergel E, Nikolsky E. Ticagrelor: an investigational oral antiplatelet treatment for reduction of major adverse cardiac events in patients with acute coronary syndrome. Vasc Health Risk Manag 2010 Oct 21; 6: 963-977.
64. Schö mig A. Ticagrelor - is there need for a new player in the antiplatelet-therapy field? N Engl J Med 2009 Sep 10; 361 (11): 1108-1111.
65. Gurbel PA, Kereiakes DJ, Tantry US. Ticagrelor for the treatment of arterial thrombosis. Expert Opin Pharmacother 2010 Sep; 11 (13): 2251-2259.
66. Duggan ST, Keating GM. Prasugrel: a review of its use in patients with acute coronary syndromes undergoing percutaneous coronary intervention. Drugs 2009; 69 (12): 1707-1726.
67. Wijns W, Kolh P, Danchin N, et al. Guidelines on myocardial revascularization: the Task Force on Myocardial Revascularization of the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS). Eur Heart J 2010 Oct; 31 (20): 2501-2555.
68. Bristol-Myers Squibb Pharmaceuticals Ltd. Plavix filmcoated tablets: summary of product characteristics [online]. Available from URL: http://www.medicines.org.uk [Accessed 2011 Apr 6].
69. Eli Lilly and Company Limited. Efient 5mg & 10 mg filmcoated tablets: summary of product characteristics [online]. Available from URL: http://www.medicines.org.uk [Accessed 2011 Apr 6].
70. Daiichi Sankyo, Inc. and Eli Lilly and Company. Effient (prasugrel) tablets: US prescribing information [online]. Available from URL: http://www.accessdata.fda.gov/drugsatfda-docs/ label/2010/022307s002lbl.pdf [Accessed 2011 Apr 6].
71. Tomoda H. Ticagrelor versus clopidogrel in acute coronary syndromes [letter]. N Engl J Med 2009 Dec 10; 361 (24): 2385; author reply 2387-2388.
72. Serebruany VL. Adenosine release: a potential explanation for the benefits of ticagrelor in the PLATelet inhibition and clinical Outcomes trial? Am Heart J 2011 Jan; 161 (1): 1-4.
73. Serebruany VL. The TRITON versus PLATO trials: differences beyond platelet inhibition. Thromb Haemost 2010 Feb; 103 (2): 259-261.
74. Rosenstein RS, Parra D. Ticagrelor versus clopidogrel in acute coronary syndromes [letter]. N Engl JMed 2009 Dec 10; 361 (24): 2385-6; author reply 2387-2388.
75. Liu T, Stern C. PLATO trial. California Pharmacist 2010 Spring; LVII (2): 46-48.
76. Bhatt DL, Cryer BL, Contant CF, et al. Clopidogrel with or without omeprazole in coronary artery disease. N Engl J Med 2010 Nov 11; 363 (20): 1909-1917.
77. AstraZeneca. 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) [Clin icalTrials.gov identifier NCT01225562]. US National Institutes of Health, ClinicalTrials.gov [online]. Available from URL: http://www.clinicaltrials.gov [Accessed 2011 Feb 2].
78. Siller-Matula JM, Krumphuber J, Jilma B. Pharmacokinetic, pharmacodynamic and clinical profile of novel antiplatelet drugs targeting vascular diseases. Br J Pharmacol 2010 Feb 1; 159 (3): 502-517.
79. Biondi-Zoccai G, Lotrionte M, Agostoni P, et al. Is ticagrelor superior to prasugrel for the treatment of acute coronary syndromes? Evidence from a 32,893-patient adjusted indirect comparison meta-analysis [abstract no. P1351]. Eur Heart J 2010 Sep; 31 Suppl. 1: 203.
80. AstraZeneca. Extended drug utilization study among patients exposed to ticagrelor, clopidogrel and prasugrel [ClinicalTrials.gov identifier NCT01276275]. US National Institutes of Health, ClinicalTrials.gov [online]. Available from URL: http://www.clinicaltrials.gov [Accessed 2011 Feb 2].
81. Kolansky DM. Acute coronary syndromes: morbidity, mortality, and pharmacoeconomic burden. Am J Manag Care 2009 Mar; 15 (2 Suppl.): S36-41.
82. Dawkins S, Adlam D, Prendergast B. New antiplatelet regimes for acute coronary syndrome management: high cost and low cost options [abstract no. P1340]. EurHeart J 2010 Sep; 31 Suppl. 1: 199-200