Skip to main content
SpringerLink
Log in

Cangrelor: A Review in Percutaneous Coronary Intervention

  • Adis Drug Evaluation
  • Published:
Drugs Aims and scope Submit manuscript

Abstract

Cangrelor (Kengrexal®, Kengreal™) is an intravenously administered P2Y12 receptor inhibitor. It is direct-acting and reversible, with a very rapid onset and offset of action. The randomized, double-blind, multinational, phase III CHAMPION PHOENIX trial compared the efficacy of intravenous cangrelor with that of oral clopidogrel in patients requiring percutaneous coronary intervention (PCI) for stable angina pectoris, a non-ST-segment elevation acute coronary syndrome or ST-segment elevation myocardial infarction (MI). The primary composite efficacy endpoint of death from any cause, MI, ischaemia-drive revascularization or stent thrombosis in the 48 h following randomization occurred in significantly fewer cangrelor than clopidogrel recipients. The rate of severe or life-threatening non-coronary artery bypass graft-related, GUSTO-defined bleeding at 48 h did not significantly differ between cangrelor and clopidogrel recipients. In conclusion, intravenous cangrelor is an important new option for use in patients undergoing PCI who have not been treated with oral P2Y12 inhibitors.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Wallentin L. P2Y12 inhibitors: differences in properties and mechanisms of action and potential consequences for clinical use. Eur Heart J. 2009;30(16):1964–77.

    Article  CAS  PubMed  Google Scholar 

  2. Levine GN, Bates ER, Blankenship JC, et al. 2011 ACCF/AHA/SCAI guideline for percutaneous coronary intervention: a report of the American College of Cardiology Foundation/American Heart Association task force on practice guidelines and the Society for Cardiovascular Angiography and Interventions. Circulation. 2011;124(23):e574–651.

    Article  PubMed  Google Scholar 

  3. O’Gara PT, Kushner FG, Ascheim DD, et al. 2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction: executive summary. A report of the American College of Cardiology Foundation/American Heart Association task force on practice guidelines. Circulation. 2013;127(4):529–55.

    Article  PubMed  Google Scholar 

  4. Windecker S, Kolh P, Alfonso F, et al. 2014 ESC/EACTS 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). Developed with the special contribution of the European Association of Percutaneous Cardiovascular Interventions (EAPCI). Eur Heart J. 2014;35(37):2541–619.

    Article  PubMed  Google Scholar 

  5. Lhermusier T, Baker NC, Waksman R. Overview of the 2014 Food and Drug Administration Cardiovascular and Renal Drugs Advisory Committee meeting regarding cangrelor. Am J Cardiol. 2015;115(8):1154–61.

    Article  PubMed  Google Scholar 

  6. Waite LH, Phan YL, Spinler SA. Cangrelor: a novel intravenous antiplatelet agent with a questionable future. Pharmacotherapy. 2014;34(10):1061–76.

    Article  CAS  PubMed  Google Scholar 

  7. European Medicines Agency. Kengrexal (cangrelor): EU summary of product characteristics. 2015. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/003773/WC500188098.pdf. Accessed 15 June 2015.

  8. The Medicines Company. Kengreal™ (cangrelor) for injection, for intravenous use: US prescribing information. 2015. http://www.kengreal.com/pdfs/kengreal-us-prescribing-information.pdf. Accessed 24 June 2015.

  9. Xiang B, Zhang G, Ren H, et al. The P2Y12 antagonists, 2MeSAMP and cangrelor, inhibit platelet activation through P2Y12/Gi-dependent mechanism. PLoS One. 2012;7(12):e51037.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  10. Akers WS, Oh JJ, Oestreich JH, et al. Pharmacokinetics and pharmacodynamics of a bolus and infusion of cangrelor: a direct, parenteral P2Y12 receptor antagonist. J Clin Pharmacol. 2010;50(1):27–35.

    Article  CAS  PubMed  Google Scholar 

  11. Storey RF, Wilcox RG, Heptinstall S. Comparison of the pharmacodynamic effects of the platelet ADP receptor antagonists clopidogrel and AR-C69931MX in patients with ischaemic heart disease. Platelets. 2002;13(7):407–13.

    Article  CAS  PubMed  Google Scholar 

  12. Storey RF, Oldroyd KG, Wilcox RG. Open multicentre study of the P2T receptor antagonist AR-C69931MX assessing safety, tolerability and activity in patients with acute coronary syndromes. Thromb Haemost. 2001;85(3):401–7.

    CAS  PubMed  Google Scholar 

  13. 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):689 e1–e10.

  14. Ingall AH, Dixon J, Bailey A, et al. Antagonists of the platelet P2T receptor: a novel approach to antithrombotic therapy. J Med Chem. 1999;42(2):213–20.

    Article  CAS  PubMed  Google Scholar 

  15. Srinivasan S, Mir F, Huang J-S, et al. The P2Y12 antagonists, 2-methylthioadenosine 5′-monophosphate triethylammonium salt and cangrelor (ARC69931MX), can inhibit human platelet aggregation through a Gi-independent increase in cAMP levels. J Biol Chem. 2009;284(24):16108–17.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  16. Ferreiro J, Ueno M, Tello-Montoliu A, et al. Effects of cangrelor in coronary artery disease patients with and without diabetes mellitus: an in vitro pharmacodynamic investigation. J Thromb Thrombolysis. 2013;35(2):155–64.

    Article  CAS  PubMed  Google Scholar 

  17. Angiolillo DJ, Schneider DJ, Bhatt DL, et al. Pharmacodynamic effects of cangrelor and clopidogrel: the platelet function substudy from the cangrelor versus standard therapy to achieve optimal management of platelet inhibition (CHAMPION) trials. J Thromb Thrombolysis. 2012;34(1):44–55.

    Article  CAS  PubMed  Google Scholar 

  18. Steinhubl SR, Oh JJ, Oestreich JH, et al. Transitioning patients from cangrelor to clopidogrel: pharmacodynamic evidence of a competitive effect. Thromb Res. 2008;121(4):527–34.

    Article  CAS  PubMed  Google Scholar 

  19. Green CL, Whellan DJ, Lambe L, et al. Electrocardiographic safety of cangrelor, a new intravenous antiplatelet agent: a randomized, double-blind, placebo- and moxifloxacin-controlled thorough QT study. J Cardiovasc Pharmacol. 2013;62(5):466–78.

    Article  CAS  PubMed  Google Scholar 

  20. Dovlatova NL, Jakubowski JA, Sugidachi A, et al. The reversible P2Y12 antagonist cangrelor influences the ability of the active metabolites of clopidogrel and prasugrel to produce irreversible inhibition of platelet function. J Thromb Haemost. 2008;6(7):1153–9.

    Article  CAS  PubMed  Google Scholar 

  21. Schneider DJ, Seecheran N, Raza SS, et al. Pharmacodynamic effects during the transition between cangrelor and prasugrel. Coron Artery Dis. 2015;26(1):42–8.

    Article  PubMed  Google Scholar 

  22. Schneider DJ, Agarwal Z, Seecheran N, et al. Pharmacodynamic effects during the transition between cangrelor and ticagrelor. JACC Cardiovasc Interv. 2014;7(4):435–42.

    Article  PubMed  Google Scholar 

  23. Harrington RA, Stone GW, McNulty S, et al. Platelet inhibition with cangrelor in patients undergoing PCI. N Engl J Med. 2009;361(24):2318–29.

    Article  CAS  PubMed  Google Scholar 

  24. Bhatt DL, Lincoff AM, Gibson CM, et al. Intravenous platelet blockade with cangrelor during PCI. N Engl J Med. 2009;361(24):2330–41.

    Article  CAS  PubMed  Google Scholar 

  25. Leonardi S, Mahaffey KW, White HD, et al. Rationale and design of the Cangrelor versus standard therapy to acHieve optimal Management of Platelet InhibitiON PHOENIX trial. Am Heart J. 2012;163(5):768–76.e2.

  26. Leonardi S, Truffa AAM, Neely ML, et al. A novel approach to systematically implement the universal definition of myocardial infarction: insights from the CHAMPION PLATFORM trial. Heart. 2013;99(17):1282–7.

    Article  CAS  PubMed  Google Scholar 

  27. Thygesen K, Alpert JS, Jaffe AS, et al. Third universal definition of myocardial infarction. Circulation. 2012;126(16):2020–35.

    Article  PubMed  Google Scholar 

  28. Thygesen K, Alpert JS, White HD, et al. Universal definition of myocardial infarction. Circulation. 2007;116(22):2634–53.

    Article  PubMed  Google Scholar 

  29. White HD, Chew DP, Dauerman HL, et al. Reduced immediate ischemic events with cangrelor in PCI: a pooled analysis of the CHAMPION trials using the universal definition of myocardial infarction. Am Heart J. 2012;163(2):182–90 e4.

  30. Bhatt DL, Stone GW, Mahaffey KW, et al. Effect of platelet inhibition with cangrelor during PCI on ischemic events. N Engl J Med. 2013;368(14):1303–13.

    Article  CAS  PubMed  Google Scholar 

  31. Généreux P, Stone GW, Harrington RA, et al. Impact of intraprocedural stent thrombosis during percutaneous coronary intervention: insights from the CHAMPION PHOENIX Trial (clinical trial comparing cangrelor to clopidogrel standard of care therapy in subjects who require percutaneous coronary intervention). J Am Coll Cardiol. 2014;63(7):619–29.

    Article  PubMed  Google Scholar 

  32. White HD, Bhatt DL, Gibson CM, et al. Outcomes with cangrelor versus clopidogrel on a background of bivalirudin: insights from the CHAMPION PHOENIX (a clinical trial comparing cangrelor to clopidogrel standard therapy in subjects who require percutaneous coronary intervention [PCI]). JACC Cardiovasc Interv. 2015;8(3):424–33.

    Article  PubMed  Google Scholar 

  33. O’Donoghue ML, Bhatt DL, Stone G, et al. The efficacy, safety, and net clinical benefit of cangrelor in women undergoing elective or urgent PCI: insights from the CHAMPION-PHOENIX trial [abstract no. 1139-083]. J Am Coll Cardiol. 2015;65(10 Suppl):A104.

    Article  Google Scholar 

  34. Cavender M, Bhatt D, Stone G, et al. Cangrelor in elderly patients endergoing PCI: findings from CHAMPION-PHOENIX [abstract no. 2101-286 ]. J Am Coll Cardiol. 2015;65(10 Suppl):A1773.

    Article  Google Scholar 

  35. Steg PG, Bhatt DL, Hamm CW, et al. Effect of cangrelor on periprocedural outcomes in percutaneous coronary interventions: a pooled analysis of patient-level data. Lancet. 2013;382(9909):1981–92.

    Article  CAS  PubMed  Google Scholar 

  36. Angiolillo DJ, Bhatt DL, Steg PG, et al. Impact of cangrelor overdosing on bleeding complications in patients undergoing percutaneous coronary intervention: insights from the CHAMPION trials. J Thromb Thrombolysis. 2015;. doi:10.1007/s11239-015-1233-3.

    PubMed Central  Google Scholar 

  37. Bristol-Myers Squibb/Sanofi. Plavix (clopidogrel bisulfate) tablets: US prescribing information. 2013. http://www.bms.com/. Accessed 16 Apr 2015.

  38. Eli Lilly and Company. Effient (prasugrel) tablets for oral use: US prescribing information. 2013. http://www.effient.com/. Accessed 16 Apr 2015.

  39. AstraZeneca. Brilinta® (ticagrelor) tablets for oral use: US prescribing information. 2015. http://www.brilinta.com/. Accessed 16 Apr 2015.

  40. Parodi G, Bellandi B, Xanthopoulou I, et al. Morphine is associated with a delayed activity of oral antiplatelet agents in patients with ST-elevation acute myocardial infarction undergoing primary percutaneous coronary intervention. Circ Cardiovasc Interv. 2015;8(1):e001593.

    Article  PubMed  Google Scholar 

  41. Lange RA, Hillis LD. The duel between dual antiplatelet therapies. N Engl J Med. 2013;368(14):1356–7.

    Article  CAS  PubMed  Google Scholar 

  42. European Medicines Agency. Plavix (clopidogrel): EU summary of product characteristics. 2015. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000174/WC500042189.pdf. Accessed 29 June 2015.

  43. European Medicines Agency. Kengrexal (cangrelor): EU public assessment report. 2015. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Public_assessment_report/human/003773/WC500188100.pdf. Accessed 15 June 2015.

  44. Wallentin L, Becker RC, Budaj A, et al. Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med. 2009;361(11):1045–57.

    Article  CAS  PubMed  Google Scholar 

  45. Wiviott SD, Braunwald E, McCabe CH, et al. Prasugrel versus clopidogrel in patients with acute coronary syndromes. N Engl J Med. 2007;357(20):2001–15.

    Article  CAS  PubMed  Google Scholar 

  46. European Medicines Agency. Brilique (ticagrelor): EU summary of product characteristics. 2014. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/001241/WC500100494.pdf. Accessed 29 June 2015.

  47. European Medicines Agency. Efient (prasugrel): EU summary of product characteristics. 2014. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000984/WC500021971.pdf. Accessed 29 June 2015.

  48. Tamborini Permunian E, Riva N, Guasti L, et al. Cangrelor for the treatment of arterial thrombosis: Pharmacokinetics/pharmacodynamics and clinical data. Expert Opin Drug Metab Toxicol. 2015;11(4):625–37.

  49. Angiolillo DJ, Firstenberg MS, Price MJ, et al. Bridging antiplatelet therapy with cangrelor in patients undergoing cardiac surgery: a randomized controlled trial. JAMA. 2012;307(3):265–74.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  50. Firstenberg MS, Dyke CM, Angiolillo DJ, et al. Safety and efficacy of cangrelor, an intravenous, short-acting platelet inhibitor in patients requiring coronary artery bypass surgery. Heart Surg Forum. 2013;16(2):61–70.

    Google Scholar 

  51. Food and Drug Administration. FDA briefing document for the cardiovascular and renal drugs advisory committee (CRDAC): cangrelor injection. 2014. http://www.fda.gov. Accessed 1 Apr 2015.

  52. Food and Drug Administration. FDA briefing document for the cardiovascular and renal drugs advisory committee (CRDAC): Kengreal (cangrelor) for injection. 2015. http://www.fda.gov. Accessed 14 Apr 2015.

Download references

Disclosure

The preparation of this review was not supported by any external funding. During the peer review process, the manufacturer of the agent under review was offered an opportunity to comment on this article. Changes resulting from comments received were made by the author on the basis of scientific and editorial merit. Gillian Keating is a salaried employee of Adis/Springer.

Author information

Authors and Affiliations

  1. Springer, Private Bag 65901, Mairangi Bay, 0754, Auckland, New Zealand

    Gillian M. Keating

Authors
  1. Gillian M. Keating
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Gillian M. Keating.

Additional information

The manuscript was reviewed by: S. Leonardi, Department of Cardiology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy; A. Mandurino-Mirizzi, University of Pavia, Pavia, Italy; D. J. Schneider, Cardiology Unit, Cardiovascular Research Institute, Department of Medicine, University of Vermont, Colchester, VT, USA.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Keating, G.M. Cangrelor: A Review in Percutaneous Coronary Intervention. Drugs 75, 1425–1434 (2015). https://doi.org/10.1007/s40265-015-0445-3

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40265-015-0445-3

Keywords

Search

Navigation