Use of Alternative Antiplatelet Agents for Clopidogrel Hypersensitivity

Author(s): Ayesha Ather, Craig J. Beavers*

Journal Name: Current Vascular Pharmacology

Volume 17 , Issue 2 , 2019

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Graphical Abstract:


Clopidogrel is a widely used agent for secondary prevention of vascular events and is a cornerstone of dual antiplatelet therapy in patients with acute coronary syndrome (ACS) post coronary stent implantation. Hypersensitivity reactions to clopidogrel are well documented and may range from localized to systemic in presentation. This can lead to discontinuation of therapy, thus increasing the risk of vascular events. The authors have developed recommendations for potential alternative agents for the management of clopidogrel hypersensitivity reactions. Proposed strategies include treatment with an alternative P2Y12 inhibitor, cilostazol or warfarin.

Keywords: Clopidogrel, hypersensitivity, prasugrel, ticagrelor, cilostazol, warfarin, stenting, rash.

Campbell KL, Cohn JR, Savage MP. Clopidogrel hypersensitivity: Clinical challenges and options for management. Expert Rev Clin Pharmacol 2010; 3: 553-61.
Campbell KL, Cohn JR, Fischman DL, et al. Management of clopidogrel hypersensitivity without drug interruption. Am J Cardiol 2011; 107: 812-6.
Cheema AN, Mohammad A, Hong T, et al. Characterization of clopidogrel hypersensitivity reactions and management with oral steroids without clopidogrel discontinuation. J Am Coll Cardiol 2011; 58: 1445-54.
Manchette AM, Drucker AG, Januzzi JL. Acute coronary syndrome antiplatelet alternatives in clopidogrel allergy. Pharmacotherapy 2014; 34: e152-6.
El-Beyrouty C, Spinler SA. Cilostazol for prevention of thrombosis and restenosis after intracoronary stenting. Ann Pharmacother 2001; 35: 1108-13.
Han Y, Wang S, Li Y, et al. Cilostazol improves long-term outcomes after coronary stent implantation. Am Heart J 2005; 150: 568.
Lee SW, Park SW, Hong MK, et al. Comparison of cilostazol and clopidogrel after successful coronary stenting. Am J Cardiol 2005; 95: 859-62.
Park SJ, Shim WH, Ho DS, et al. A paclitaxel-eluting stent for the prevention of coronary restenosis. N Engl J Med 2003; 348: 1537-45.
Sekiguchi M, Hoshizaki H, Adachi H, et al. Effects of antiplatelet agents on subacute thrombosis and restenosis after successful coronary stenting: A randomized comparison of ticlopidine and cilostazol. Circ J 2004; 68: 610-4.
Matsumoto M. Cilostazol in secondary prevention of stroke: Impact of the Cilostazol Stroke Prevention Study. Atheroscler Suppl 2005; 6: 33-40.
Huang Y, Cheng Y, Wu J, et al. Cilostazol as an alternative to aspirin after ischaemic stroke: A randomised, double-blind, pilot study. Lancet Neurol 2008; 7: 494-9.
Shinohara Y, Katayama Y, Uchiyama S, et al. Cilostazol for prevention of secondary stroke (CSPS 2): An aspirin-controlled, double-blind, randomised non-inferiority trial. Lancet Neurol 2010; 9: 959-68.
Vandvik PO, Lincoff AM, Gore JM, et al. Primary and secondary prevention of cardiovascular disease: Antithrombotic therapy and prevention of thrombosis, 9th ed: American college of chest physicians evidence-based clinical practice guidelines. Chest 2012; 141(2 Suppl): 637-68.
Paradiso-Hardy FL, Angelo CM, Lanctôt KL, Cohen EA. Hematologic dyscrasia associated with ticlopidine therapy: Evidence for causality. CMAJ 2000; 163: 1441-8.
Moussa I, Oetgen M, Roubin G, et al. Effectiveness of clopidogrel and aspirin versus ticlopidine and aspirin in preventing stent thrombosis after coronary stent implantation. Circulation 1999; 99: 2364-6.
Mueller C, Roskamm H, Neumann FJ, et al. A randomized comparison of clopidogrel and aspirin versus ticlopidine and aspirin after the placement of coronary artery stents. J Am Coll Cardiol 2003; 41: 969-73.
Bertrand ME, Rupprecht HJ, Urban P, Gershlick AH. Double- blind study of the safety of clopidogrel with and without a loading dose in combination with aspirin compared with ticlopidine in combination with aspirin after coronary stenting: the clopidogrel aspirin stent international cooperative study (CLAS- SICS). Circulation 2000; 102: 624-9.
Owen P, Garner J, Hergott L, Page RL 2nd. Clopidogrel desensitization: case report and review of published protocols. Pharmacotherapy 2008; 28: 259-70.
Lokhandwala JO, Best PJ, Butterfield JH, et al. Frequency of allergic or hematologic adverse reactions to ticlopidine among patients with allergic or hematologic adverse reactions to clopidogrel. Circ Cardiovasc Interv 2009; 2: 348-51.
Wiviott SD, Braunwald E, McCabe CH, et al. Prasugrel versus clopidogrel in patients with acute coronary syndromes. N Engl J Med 2007; 357: 2001-15.
Roe MT, Armstrong PW, Fox KA, et al. Prasugrel versus clopidogrel for acute coronary syndromes without revascularization. N Engl J Med 2012; 367: 1297-309.
Binazon O, Dubois-Gauche A, Nanau RM, Neuman MG. Efficacy and safety of platelet inhibitors. J Pharm Pharm Sci 2013; 16: 1-39.
Siu H, Kaliyadan A, Fischman DL, Nardone E, Poll D, Savage MP. Use of prasugrel in the setting of clopidogrel hypersensitivity: Case report and systematic review of the literature. Platelets 2016; 27: 824-7.
Levine GN, Bates ER, Bittl JA, et al. 2016 ACC/AHA guideline focused update on duration of dual antiplatelet therapy in patients with coronary artery disease: A report of the American college of cardiology/American heart association task force on clinical practice guidelines. J Thorac Cardiovasc Surg 2016; 152: 1243-75.
Wallentin L, Becker RC, Budaj A, et al. Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med 2009; 361: 1045-57.
Hiatt WR, Fowkes FG, Heizer G, et al. Ticagrelor versus Clopidogrel in symptomatic peripheral artery disease. N Engl J Med 2017; 376: 32-40.
Maybrook RJ, Fischer R, Deibert B, et al. Ticagrelor-induced acute generalized exanthematous pustulosis. Int J Cardiol 2015; 191: 11-2.
Harris JR, Coons JC. Ticagrelor use in a patient with a documented clopidogrel hypersensitivity. Ann Pharmacother 2014; 48: 1230-3.
Dai J, Lyu S, Ge C. Hypersensitivity to ticagrelor and low response to clopidogrel: A case report. Asia Pac Allergy 2017; 7: 51-3.
Leon MB, Baim DS, Popma JJ, et al. A clinical trial comparing three antithrombotic-drug regimens after coronary-artery stenting. Stent Anticoagulation Restenosis Study Investigators. N Engl J Med 1998; 339: 1665-71.
Schömig A, Neumann FJ, Kastrati A, et al. A randomized comparison of antiplatelet and anticoagulant therapy after the placement of coronary-artery stents. N Engl J Med 1996; 334: 1084-9.
Mehta SR, Tanguay JF, Eikelboom JW, 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 randomized factorial trial. Lancet 2010; 376: 1233-43.
Mangiacapra F, Muller O, Ntalianis A, et al. Comparison of 600 versus 300-mg Clopidogrel loading dose in patients with ST-segment elevation myocardial infarction undergoing primary coronary angioplasty. Am J Cardiol 2010; 106: 1208-11.

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Article Details

Year: 2019
Page: [127 - 132]
Pages: 6
DOI: 10.2174/1570161116666180730100806
Price: $65

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