Ticagrelor: A P2Y 12 antagonist for use in acute coronary syndromes

Expert Review of Clinical Pharmacology

Volumn 5, Issue 3, 2012, Pages 257-269

  Wijeyeratne, Yanushi Dullewe ^a   Joshi, Rashi ^a   Heptinstall, Stan ^a  

^a UNIVERSITY OF NOTTINGHAM   (United Kingdom)

Author keywords

acute coronary syndrome; antiplatelet therapy; clopidogrel; cyclopentyl triazolo pyrimidine; P2Y 12 antagonists; prasugrel; thienopyridine; thrombosis; ticagrelor

Indexed keywords

ACETYLSALICYLIC ACID; AR C 124910XX; CANGRELOR; CLARITHROMYCIN; CLOPIDOGREL; CYTOCHROME P450 2C19; DIGOXIN; DIPYRIDAMOLE; DRUG METABOLITE; ELINOGREL; G PROTEIN COUPLED RECEPTOR KINASE; GLYCOPROTEIN IIB; GLYCOPROTEIN IIIA; KETOCONAZOLE; PEPTIDOLEUKOTRIENE; PRASUGREL; PURINERGIC P2Y12 RECEPTOR; PYRIMIDINE NUCLEOTIDE; SIMVASTATIN; TICAGRELOR; UNCLASSIFIED DRUG; ADENOSINE; ANTITHROMBOCYTIC AGENT; DRUG DERIVATIVE; PIPERAZINE DERIVATIVE; PURINERGIC P2Y RECEPTOR ANTAGONIST; THIOPHENE DERIVATIVE; TICLOPIDINE;

ACUTE CORONARY SYNDROME; ATHEROSCLEROSIS; BLOOD OXYGEN TENSION; BRAIN HEMORRHAGE; CARDIOVASCULAR MORTALITY; CLINICAL TRIAL (TOPIC); CONFIDENCE INTERVAL; CORONARY ARTERY DISEASE; CORONARY ARTERY THROMBOSIS; DIABETES MELLITUS; DRUG EFFICACY; DRUG MARKETING; DRUG MEGADOSE; DRUG SAFETY; DRUG TOLERABILITY; DRUG WITHDRAWAL; DYSPNEA; ELECTROCARDIOGRAM; EPISTAXIS; FOOD AND DRUG ADMINISTRATION; FUNCTIONAL RESIDUAL CAPACITY; GASTROINTESTINAL HEMORRHAGE; GENETIC POLYMORPHISM; GYNECOMASTIA; HAZARD RATIO; HEART DEATH; HEART FAILURE; HEART LEFT BUNDLE BRANCH BLOCK; HEART SUPRAVENTRICULAR ARRHYTHMIA; HOSPITAL DISCHARGE; HUMAN; LOADING DRUG DOSE; LOW DRUG DOSE; MULTICENTER STUDY (TOPIC); NON ST SEGMENT ELEVATION MYOCARDIAL INFARCTION; NONHUMAN; PERCUTANEOUS CORONARY INTERVENTION; RANDOMIZED CONTROLLED TRIAL (TOPIC); RESIDUAL VOLUME; REVIEW; SKIN BLEEDING; SKIN BRUISING; ST SEGMENT ELEVATION MYOCARDIAL INFARCTION; STENT THROMBOSIS; THROMBOCYTE AGGREGATION; THROMBOCYTE FUNCTION; TOTAL LUNG CAPACITY; UNSTABLE ANGINA PECTORIS; DRUG COMBINATION; DRUG EFFECT; KAPLAN MEIER METHOD; POSTMARKETING SURVEILLANCE; THROMBOCYTE;

ACUTE CORONARY SYNDROME; ADENOSINE; ASPIRIN; BLOOD PLATELETS; CLINICAL TRIALS AS TOPIC; DRUG THERAPY, COMBINATION; HUMANS; KAPLAN-MEIER ESTIMATE; PIPERAZINES; PLATELET AGGREGATION; PLATELET AGGREGATION INHIBITORS; PRODUCT SURVEILLANCE, POSTMARKETING; PURINERGIC P2Y RECEPTOR ANTAGONISTS; THIOPHENES; TICLOPIDINE;

EID: 84861430100     PISSN: 17512433     EISSN: 17512441     Source Type: Journal    
DOI: 10.1586/ecp.12.17     Document Type: Review

References (51)

1. Centers for Disease Control and Prevention (CDC). Prevalence of coronary heart disease-United States, 2006-2010. Morb. Mortal. Wkly Rep. 60(40), 1377-1381 (2011
2. Leal J, Luengo-Fernández R, Gray AM et al. Economic burden of cardiovascular diseases in the enlarged EU. Eur. Heart J. 27(3), 1610-1619 (2006
3. Fox KAA, Dabbous OH, Goldberg RJ et al. Prediction of risk of death and myocardial infarction in the six months after presentation with acute coronary syndrome: prospective multinational observational study (GRACE). Br. Med. J. 333(7578), 1091-1094 (2006
4. Fox KAA, Carruthers KF, Dunbar DR et al. Underestimated and under-recognized: the late consequences of acute coronary syndrome (GRACE UK-Belgian study). Eur. Heart J. 31(22), 2755-2764 (2010
5. Tang EW, Wong CK, Herbison P. Global registry of acute coronary events (GRACE) hospital discharge risk score accurately predicts long-term mortality post acute coronary syndrome. Am. Heart J. 153(1), 29-35 (2007
6. Mehran R, Pocock S, Nikolsky E et al. Impact of bleeding on mortality after percutaneous coronary intervention results from a patient-level pooled analysis of the REPLACE-2 (Randomized Evaluation of PCI Linking Angiomax to Reduced Clinical Events), ACUITY (Acute Catheterization and Urgent Intervention Triage Strategy), and HORIZONS-AMI (Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction) trials. JACC Cardiovasc. Interv. 4(6), 654-664 (2011
7. Wijeyeratne YD, Heptinstall S. Antiplatelet therapy: ADP receptor antagonists. Br. J. Clin. Pharmacol. 72(4), 647-657 (2011
8. Danchin N, Aissaoui N. Pharmacologic therapy for non-ST-segment elevation acute coronary syndromes: focus on anti-thrombotic therapy. Cardiovasc. Drugs Ther. 24(4), 325-330 (2010
9. Fox SC, May JA, Shah A, Neubert U, Heptinstall S. Measurement of platelet P-selectin for remote testing of platelet function during treatment with clopidogrel and/or aspirin. Platelets 20(4), 250-259 (2009
10. Sofi F, Marcucci R, Gori AM et al. Clopidogrel non-responsiveness and risk of cardiovascular morbidity. An updated meta-analysis. Thromb. Haemost. 103(4), 841-848 (2010
11. Kunadian B, Thornley AR, Tanos M, Dunning J. Should clopidogrel be stopped prior to urgent cardiac surgery? Interact. Cardiovasc. Thorac. Surg. 5(5), 630-636 (2006
12. Wiviott SD, Braunwald E, McCabe CH et al. Prasugrel versus clopidogrel in patients with acute coronary syndromes. N. Engl. J. Med. 357(20), 2001-2015 (2007
13. van Giezen JJ, Nilsson L, Berntsson P et al. Ticagrelor binds to human P2Y(12) independently from ADP but antagonizes ADP-induced receptor signaling and platelet aggregation. J. Thromb. Haemost. 7(9), 1556-1565 (2009
14. Teng R, Oliver S, Hayes MA, Butler K. Absorption, distribution, metabolism, and excretion of ticagrelor in healthy subjects. Drug Metab. Dispos. 38(9), 1514-1521 (2010
15. Husted S, van Giezen JJ. Ticagrelor: the first reversibly binding oral P2Y12 receptor antagonist. Cardiovasc. Ther. 27(4), 259-274 (2009
16. Högberg C, Svensson H, Gustafsson R, Eyjolfsson A, Erlinge D. The reversible oral P2Y12 antagonist AZD6140 inhibits ADP-induced contractions in murine and human vasculature. Int. J. Cardiol. 142(2), 187-192 (2010
17. van Giezen JJ, Sidaway J, Glaves P, Kirk I, Björkman JA. Ticagrelor inhibits adenosine uptake in vitro and enhances adenosine-mediated hyperemia responses in a canine model. J. Cardiovasc. Pharmacol. Ther. doi:10.1177/1074248411410883 (2011) (Epub ahead of print
18. Ohman J, Kudira R, Albinsson S et al. Ticagrelor induces adenosine triphosphate release from human red blood cells. Biochem. Biophys. Res. Commun. 418(4), 754-758 (2012
19. Burki NK, Dale WJ, Lee LY. Intravenous adenosine and dyspnea in humans. J. Appl. Physiol. 98(1), 180-185 (2005
20. Iyú, D, Glenn JR, White AE, Fox SC, Heptinstall S. Adenosine derived from ADP can contribute to inhibition of platelet aggregation in the presence of a P2Y12 antagonist. Arterioscl. Thromb. Vasc. Biol. 31(2), 416-422 (2011
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. 27(9), 1038-1047 (2006
22. 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. 50(19), 1844-1851 (2007
23. 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. 50(19), 1852-1856 (2007).
24. Gurbel PA, Bliden KP, Butler K 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(25), 2577-2585 (2009
25. 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 121(10), 1188-1199 (2010
26. James S, Akerblom A, Cannon CP et al. Comparison of ticagrelor, the first reversible oral P2Y(12) 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. 157(4), 599-605 (2009
27. Wallentin L, Becker RC, Budaj A et al. Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N. Engl. J. Med. 361(11), 1045-1057 (2009
28. 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. 56(18), 1456-1462 (2010
29. Butler K, Teng R. Pharmacokinetics, pharmacodynamics, safety and tolerability of multiple ascending doses of ticagrelor in healthy volunteers. Br. J. Clin. Pharmacol. 70(1), 65-77 (2010
30. Butler K. Pharmacokinetics, pharmacodynamics, and safety of ticagrelor in volunteers with severe renal impairment. J. Clin. Pharmacol. doi:10.1177/0091270011415526 (2011) (Epub ahead of print
31. Teng R, Mitchell PD, Butler K. Lack of significant food effect on the pharmacokinetics of ticagrelor in healthy volunteers. J. Clin. Pharm. Ther. doi:10.1111/j.1365-2710.2011.01307.x (2011) (Epub ahead of print
32. Disney BR, Watson RDS, Blann AD, Lip GYH, Anderson MR. Proton pump inhibitors with clopidogrel. Evidence for and against a clinically-important interaction. Aliment. Pharmacol. Ther. 33(7), 758-767 (2011
33. Goodman SG, Clare R, Pieper KS et al. Association of proton pump inhibitor use on cardiovascular outcomes with clopidogrel and ticagrelor: insights from PLATO. Circulation 125(8), 978-986 (2012
34. Serebruany VL. Viewpoint: paradoxical excess mortality in the PLATO trial should be independently verified. Thromb. Haemost. 105(5), 752-759 (2011
35. Wallentin L, Becker RC, James SK, Harrington RA. The PLATO trial reveals further opportunities to improve outcomes in patients with acute coronary syndrome. Thromb. Haemost. 105(5), 760-762 (2011
36. Ohman EM, Roe MT. Explaining the unexpected: insights from the Platelet Inhibition and Clinical Outcomes (PLATO) trial comparing ticagrelor and clopidogrel. Thromb. Haemost. 105(5), 763-765 (2011
37. Mahaffey KW, Wojdyla DM, Carroll K et al. Ticagrelor compared with clopidogrel by geographic region in the platelet inhibition and patient outcomes (PLATO) trial. Circulation 124(5), 544-554 (2011
38. 2+ responses and platelet aggregation by the P2Y12 receptor antagonists AR-C69931MX and clopidogrel is enhanced by prostaglandin E1. Cell Calcium 35(1), 39-46 (2004
39. Cattaneo M, Lecchi A. Inhibition of the platelet P2Y12 receptor for adenosine diphosphate potentiates the antiplatelet effect of prostacyclin. J. Thromb. Haemost. 5(3), 577-582 (2007
40. Iyú D, Glenn JR, White AE, Fox SC, Dovlatova N, Heptinstall S. P2Y(12) and EP3 antagonists promote the inhibitory effects of natural modulators of platelet aggregation that act via cAMP. Platelets 22(7), 504-515 (2011
41. 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 375(9711), 283-293 (2010
42. Steg PG, James S, Harrington RA 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(21), 2131-2141 (2010
43. Armstrong PW, Siha H, Fu Y et al. Elevation acute coronary syndromes in PLATO: insights from the ECG substudy. Circulation 125(3), 514-521 (2012
44. Held C, Asenblad 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. 57(6), 672-684 (2011
45. James SK, Roe MT, Cannon CP et al. Ticagrelor versus clopidogrel in patients with acute coronary syndromes intended for noninvasive management: substudy from prospective randomised Platelet Inhibition and Patient Outcomes (PLATO) trial. Br. Med. J. 342, D3527 (2011
46. James S, Angiolillo DJ, Cornel JH et al. Ticagrelor vs clopidogrel in patients with acute coronary syndromes and diabetes: a substudy from the Platelet Inhibition and Patient Outcomes (PLATO) trial. Eur. Heart J. 31(24), 3006-3016 (2010
47. 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 122(11), 1056-1067 (2010
48. Becker RC, Bassand JP, Budaj A et al. Bleeding complications with the P2Y12 receptor antagonists clopidogrel and ticagrelor in the Platelet Inhibition and Patient Outcomes (PLATO) trial. Eur. Heart J. 32, 2933-2944 (2011
49. Storey RF, Becker RC, Harrington RA et al. Pulmonary function in patients with acute coronary syndrome treated with ticagrelor or clopidogrel (from the Platelet Inhibition and Patient Outcomes [PLATO] pulmonary function substudy). Am. J. Cardiol. 108(11), 1542-1546 (2011
50. Butler K, Teng R. Evaluation and characterization of the effects of ticagreloron serum and urinary uric acid in healthy volunteers. Clin. Pharmacol. Ther. 91(2), 264-271 (2012
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. 39(4), 703-710 (2011)