Cangrelor - rising from the ashes: a phoenix story
DOI:
https://doi.org/10.18203/2319-2003.ijbcp20160134Keywords:
Cangrelor, Clopidogrel, Novel anti-platelet, PCI, Stent thrombosesAbstract
Cangrelor is a novel intravenous antiplatelet agent that has been approved for usage in the setting of percutaneous coronary revascularization in patients with acute coronary syndrome. The drug was evaluated in three major trials namely Champion-Platform, Champion-PCI and Champion Phoenix with a total of 25,107 patients. Although there was a reduction in the incidence of ischemia driven revascularization, Q wave MI and stent thromboses in the first 48 hours among cangrelor users as compared to clopidogrel, there was no difference in the incidence of all-cause mortality or myocardial infarction. In terms of safety, cangrelor does not appear to have a higher bleeding risk. A distinct appeal with cangrelor is its unique pharmacokinetic property of having a rapid onset and offset of action. The drug would also have a niche role among patients with challenges to oral drug administration as in mechanically ventilated patients and those with severe vomiting. Although the drug managed to rise against odds in getting regulatory approval from the FDA, it remains to be seen if this could become a frontline agent among the current array of anti-platelet molecules.References
Klein LW. Are drug-eluting stents the preferred treatment for multivessel coronary artery disease? J Am Coll Cardiol. 2006;47(1):22-6.
Windecker S, Kolh P, Alfonso F, Collet JP, Cremer J, 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.
Kubica A, Kozinski M, Grzesk G, Fabiszak T, Navarese EP, Goch A. Genetic determinants of platelet response to clopidogrel. J Thromb Thrombolysis. 2011;32(4):459-66.
Jeong YH, Tantry US, Kim IS, Koh JS, Kwon TJ, Park Y, et al. Effect of CYP2C19*2 and *3 loss-of-function alleles on platelet reactivity and adverse clinical events in East Asian acute myocardial infarction survivors treated with clopidogrel and aspirin. Circ Cardiovasc Interv. 2011;4(6):585-94.
Franchi F, Rollini F, Park Y, Angiolillo DJ. Novel Antiplatelet Agents: The Current State and What Is Coming Down the Pike. Prog Cardiovasc Dis, 2015
Rafeedheen R, Bliden KP, Liu F, Tantry US, Gurbel PA. Novel antiplatelet agents in cardiovascular medicine. Curr Treat Options Cardiovasc Med. 2015;17(6):383.
Cattaneo M. The clinical relevance of response variability to antiplatelet therapy. Hematol Educ Program Am Soc Hematol Am Soc Hematol Educ Program. 2011;2011:70-5.
Michelson AD. Advances in antiplatelet therapy. Hematol Educ Program Am Soc Hematol Am Soc Hematol Educ Program. 2011;2011:62-9.
Wallentin L. P2Y(12) inhibitors: differences in properties and mechanisms of action and potential consequences for clinical use. Eur Heart J. 2009;30(16):1964-77.
FDA Briefing document for the Cardiovascular & Renal Drugs Advisory Committee- Cangrelor- Maryland, USA. 2015:1-25.
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.
Harrington RA, Stone GW, McNulty S, White HD, Lincoff AM, Gibson CM, et al. Platelet inhibition with cangrelor in patients undergoing PCI. N Engl J Med. 2009;361(24):2318-29.
Bhatt DL, Lincoff AM, Gibson CM, Stone GW, McNulty S, Montalescot G, et al. Intravenous platelet blockade with cangrelor during PCI. N Engl J Med. 2009;361(24):2330-41.
Bhatt DL, Stone GW, Mahaffey KW, Gibson CM, Steg PG, Hamm CW, et al. Effect of platelet inhibition with cangrelor during PCI on ischemic events. N Engl J Med. 2013;368(14):1303-13.
Mega JL, Simon T, Collet JP, Anderson JL, Antman EM, Bliden K, et al. Reduced-function CYP2C19 genotype and risk of adverse clinical outcomes among patients treated with clopidogrel predominantly for PCI: a meta-analysis. JAMA. 2010;304(16):1821-30.
