Abstract
Background and Objective: The thienopyridine family includes ticlopidine, clopidogrel and prasugrel which are antiplatelet drugs largely used, mainly associated to aspirin, for treatment of acute coronary syndromes and after percutaneous coronary interventions, to avoid thrombosis. In some patients, thienpyridines may cause hypersensitivity reactions which jeopardize the optimal therapeutic and preventive approach to vascular diseases. The management of thienopyridine hypersensitivity seems to be best done as an interdisciplinary collaboration between the allergist and cardiologist.
Method: The present study investigates the management of thienopyridines hypersensitivity on the basis of published case reports and studies, comparing the pro and contro of pharmacological treatments, different desensitization protocols to thienopyridines and substitution of antiplatelet agents eaches others, according to the point of view of cardiologist and allergist. For the cardiologist, the important issues are the necessity of continuing therapy, the desired duration of therapy based on the clinical indication of the individual patient and appropriateness of using one of the alternative P2Y12 inhibitors. For the allergist, the important issues are weighing the risk and benefits of the various therapeutic options: treating “through” desensitization, or switching to an alternative agent.
Results and Conclusion: All the data seem to suggest that only working together, a cardio-allergy team of specialists may evaluate and offer the best approach to clinical decision-making for the individual patient.
Keywords: Thienopyridines, hypersensitivity, ticlopidine, clopidogrel, prasugrel, ticagrelor desensitization, premedication.
Graphical Abstract
[1]
ACC/AHA Guidelines for percutaneous coronary intervention. J. Am. Coll. Cardiol., 2001, 37, 2239i-2249i.
[3]
Girja, D.; Singh, B.D.; Komal, S. Thienopyridines: Platelets ADP receptor antagonist. J. Drug Deliv. Ther., 2011, 1, 8-16.
[4]
Dominick, J.A.; Ortiz, A.F.; Bernardo, E.; Alfonso, F.; Macaya, C.; Bass, T.; Costa, M.A. Variability in individual responsiveness to clopidogrel: Clinical implications, management, and future perspectives. J. Am. Coll. Cardiol., 2007, 49, 1505-1516.
[5]
Wallentin, L. P2Y12 inhibitors: Differences in properties and mechanisms of action and potential consequences for clinical use. Eur. Heart J., 2009, 30, 1964-1977.
[6]
Campbell, K.L.; Cohn, J.R.; Savage, M.P. Clopidogrel hypersensitivity: Clinical challenges and options for management. Expert Rev. Clin. Pharmacol., 2010, 3, 553-561.
[7]
Dobesh, P.P.; Oestreich, J.H. Ticagrelor: Pharmacokinetics, pharmaco-dynamics, clinical efficacy, and safety. Pharmacotherapy, 2014, 34, 1077-1090.
[8]
Calogiuri, G.F.; Alsowaidi, S.; Nettis, E.; Cortellini, G.; Macchia, L.; Vacca, A.; Kounis, N.G. A joint allergist/cardiologist classification for thienopyridines hypersensitivity reactions based on their symptomatic patterns and its impact on the management strategies. Int. J. Cardiol., 2016, 222, 509-514.
[9]
Campbell, K.L.; Cohn, J.R.; Fischman, D.L.; Walinski, P.; Mallya, R.; Jaffrani, W.; Savage, M.P. Management of clopidogrel hypersensitivity without drug interruption. Am. J. Cardiol., 2011, 107, 812-816.
[10]
Simpson, D.G.; Hubaytar, R.T. Hypersensitivity to drugs in the treatment of tuberculosis. Rapid desensitization using cortisone acetate. Am. Rev. Respir. Dis., 1962, 86, 738-739.
[11]
Cheema, A.; Mohammad, A.; Hong, T.; Jakubovic, H.R.; Parmar, G.S.; Sharieff, W.; Garvey, M.B.; Kutryk, M.J.; Fam, N.P.; Graham, J.J.; Chisholm, R.J. Characterization of clopidogrel hypersensitivity reactions and managment with oral steroid without clopidogrel disconntinuatiion. J. Am. Coll. Cardiol., 2011, 58, 1445-1454.
[12]
Dakik, H.A. Successful treatment of clopidogrel hypersensitivity with a seven-days taper of oral corticosteroid. Ann. Pharmacother., 2015, 49, 1077-1078.
[13]
Yang, D.C.; Feldman, D.N.; Kim, L.K.; Minutello, R.M.; Bergman, G.; Wong, S.C.; Swaminathan, R.V. A strategy of ‘treating through’ a prasugrel-induced rash. Int. J. Cardiol., 2013, 168, 4381-4382.
[14]
Cernadas, J.R.; Brockow, K.; Romano, A.; Aberer, W.; Torres, M.J.; Bircher, A.; Campi, P.; Sanz, M.L.; Castells, M.; Demoly, P.; Pichler, W.J. General considerations on rapid desensitization for drug hypersensitivity - A consensus statement. Allergy, 2010, 65, 1357-1366.
[15]
Scherer, K.; Brockow, K.; Aberer, W.; Gooi, J.H.; Demoly, P.; Romano, A.; Schnyder, B.; Whitaker, P.; Cernadas, J.S.; Bircher, A.J. Desensitization in delayed drug hypersensitivity reactions -- an EAACI position paper of the Drug Allergy Interest Group. Allergy, 2013, 68, 844-852.
[16]
Vigo, P.G.; MacDowell, A.L.; Wedner, H.J. Successful desensitization with clopidogrel after a positive skin test. Ann. Allergy Asthma Immunol., 2005, 94, 132.
[17]
Camara, M.G.; Almeda, F.Q. Clopidogrel (Plavix) desensitization: A case series. Catheter. Cardiovasc. Interv., 2005, 65, 525-527.
[18]
Lee-Wong, M.; Gadhvi, D.; Resnick, D. Clopidogrel desensitization. Ann. Allergy Asthma Immunol., 2006, 96, 756-757.
[19]
Oppedijk, B.; Odekerken, D.A. van der, Wildt. J.J.; Melissant, C.F. Rapid oral desensitisation procedure in clopidogrel hypersensitivity. Neth. Heart J., 2008, 16, 21-23.
[20]
Kammer, R.T. Successful clopidogrel desensitization after drug eluting stent implantation. J. Invasive Cardiol., 2009, 21, 134-135.
[21]
Chin, N.; Rangamuwa, K.; Mariasooai, R.; Carnes, J.; Thien, F. Oral antiplatelet agents hypersensitivity and cross reactivity managed by successful desensitization. Asia Pac. Allergy, 2015, 5, 51-54.
[22]
Owen, P.; Garner, J.; Hergott, L. Page RL 2nd. Clopidogrel desensitization: Case report and review of published protocols. Pharmacotherapy, 2008, 28, 259-270.
[23]
Sanchez-Lopez, J.; Munoz-Cano, R.; Batra, J.; Valero, A.; Picado, C. Desensitization to clopidogrel: A growing need. Allergy, 2010, 65, 279-280.
[24]
Walker, N.E.; Fasano, M.B.; Howitz, P.A. Desensitization for the management of clopidogrel hypersensitivity: Initial clinical experience. J. Invasive Cardiol., 2006, 18, 341-344.
[25]
von. Tiehl K.F.; Price, M.J.; Valencia, R.; Ludington, K.J. Teirstein, P.S.; Simon, R.A. Clopidogrel desensitization after drug-eluting stent placement. J. Am. Coll. Cardiol., 2007, 50, 2039-2043.
[26]
Doshi, R.; Enoh, A.; Antonopoulos, P.; Sattar, P. A novel, accelerated method of desensitization in a patient with a documented hypersensitivity reaction to clopidogrel. J. Cardiol. Cases, 2010, 1, e158-e160.
[27]
Fajt, M.; Petrov, A. Clopidogrel hypersensitivity. A novel multi-day outpatient oral desensitization regimen. Ann. Pharmacother., 2010, 44, 11-18.
[28]
Nam, N.J.; Chau, D.; Miller, L.M.; Canffield, R.M. Desensitization to clopidogrel and ticlopidine in two patients with coronary artery disease and indwelling drug-eluting stents. J. Allergy Clin. Immunol., 2006, 117(Suppl. 2), S126. [Abstract 495].
[29]
Barreira, P.; Cadinha, S.; Malheiro, D.; Moreira, J.P. Desensitization to clopidogrel: A tailor made protocol. Eur. Ann. Allergy Clin. Immunol., 2014, 46, 53-55.
[30]
Calogiuri, G.; Nettis, E.; Di Leo, E.; Foti, C.; Ferrannini, A.; Butani, L. Allopurinol hypersensitivity reactions: Desensitization strategies and new therapeutic alternative molecules. Inflamm. Allergy Drug Targets, 2013, 12, 19-28.
[31]
Fernando, S.L.; Assaa, D.N.A. Rapid and sequential desensitization to both aspirin and clopidogrel. Intern. Med. J., 2010, 40, 596-599.
[32]
Mutnick, J.L. Desensitization to prasugrel: Cardiology’s increased need for allergy consultation. Ann. Allergy Asthma Immunol., 2012, 108, 124-125.
[33]
Cegec, I.I.; Francetic, V.; Erdeljic Turk, K.; Makar Ausperger, M.; Aumiler Radacic, I.; Kraljickovic, I.; Cacic, I.; Likic, R. Pharmacoeconomic analysis comparing clopidogrel desensitization protocol versus ticagrelor for antithrombotic treatment in coronary artery disease patients with clopidogrel hypersensitivity after PCI. Clin. Ther., 2015, 37(Suppl.), e77.
[34]
Lokhandwala, J.; Best, P.; Butterfield, J.; Skelding, K.; Scott, T.; Blankenship, J.; Buckley, J.; Berger, P. Frequency of allergic or hematologic adverse reactions among patients with allergic or hematologic adverse reactions to clopidogrel. Circ. Cardiovasc. Interv., 2009, 2, 348-351.
[35]
Morrow, D.A.; Wiviott, S.D.; White, H.D.; Nicolau, J.C.; Bramucci, E.; Murphy, S.A.; Bonaca, M.P.; Ruff, C.T.; Scirica, B.M.; McCabe, C.H.; Antman, E.M.; Braunwald, E. Effect of the novel thienopyridine prasugrel compared with clopidogrel on spontaneous and procedural myocardial infarction in the Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition with Prasugrel-Thrombolysis in Myocardial Infarction 38: An application of the classification system from the universal definition of myocardial infarction. Circulation, 2009, 119, 2758-2764.
[36]
Siu, H.; Kaliyadan, A.; Fischman, D.L.; Nardone, E.; Poll, D.; Savage, M.P. Use of prasugrel in the setting of clopidogrel hypersensitivity. Case report and systematic review of the literature. Platelets, 2016, 27, 824-827.
[37]
Kim, S.H.; Park, S.D.; Baek, Y.S.; Lee, S.Y.; Shin, S.H.; Woo, S.I.; Kim, D.H.; Kwan, J. Prasugrel-induced hypersensitivity skin reaction. Korean Circ. J., 2014, 44, 355-357.
[38]
Deshmukh, A.J.; Pant, S.; Cook, J.; Sachdeva, R.; Rutlen, D.; Uretsky, B.F. Prasugrel-induced rash. Ann. Pharmacother., 2012, 46, 1123-1125.
[39]
Patel, T.N.; Kreindel, M.; Lincoff, A.M. Use of ticlopidine and cilostazol after intracoronary drug-eluting stent placement in a patient with previous clopidogrel-induced thrombotic thrombocytopenic purpura: A case report. J. Invasive Cardiol., 2006, 18, e211-e213.
[40]
Khangura, S.; Gordon, W.L. Prasugrel as an alternative for clopidogrel-associated neutropenia. Can. J. Cardiol., 2011, 27(869), e9-e11.
[41]
Trivier, J.M.; Caron, J.; Mathieu, M.; Cambier, N.; Rose, C. Fatal aplastic anemia associated with clopidogrel. Lancet, 2001, 357, 446.
[42]
Gutiérrez-Fernández, D.; Fuentes-Vallejo, M.S.; Rueda-Ygueravides, M.D.; Foncubierta-Fernández, A.; León-Jiménez, A. Immediate hypersensitivity and delayed hypersensitivity to clopidogrel. Allergol. Immunopathol., 2007, 35, 213-215.
[43]
Brockow, K.; Romano, A.; Blanca, M.; Ring, J.; Pichler, W.; Demoly, P. General considerations for skin test procedures in the diagnosis of drug hypersensitivity. Allergy, 2002, 57, 45-51.
[44]
Pichler, W.J.; Daubner, B.; Kawabata, T. Drug hypersensitivity: Flare-up reactions, cross-reactivity and multiple drug hypersensitivity. J. Dermatol., 2011, 38, 216-221.
[45]
Hou, X.M.; Wu, W.Y. Toxic epidermal necrolysis after percutaneous coronary intervention: Which drug is the culprit? Chin. Med. J. (Engl.), 2011, 124, 467-468.
[46]
Harris, J.R.; Cooms, J. Tigacrelor use in a patient with documented clopidogrel hypersensitivity. Ann. Pharmacother., 2014, 48, 1230-1233.
[47]
Manchette, A.M.; Drucker, A.G.; Jannuzzi, J.L. Acute coronary syndrome antiplatelet alternatives in clopidogrel allergy. Pharmacotherapy, 2014, 34, e152-e156.
[48]
Ulman, C.A.; Palmer, D.G.; Trevino, J.J.; Olsen, T.G.; Krishnamurthy, S.; Gandhi, R.K. Acute generalized exanthematous pustulosis induced by clopidogrel. Int. J. Dermatol., 2014, 53, e461-e462.
[49]
Kaufmann, M.B.; Pham, T.; Parameswaran, L.; Choy, M. Prasugrel hypersensitivity with respiratory distress and rash. Am. J. Health Syst. Pharm., 2016, 73, 1051-1057.
[50]
Quinn, K.L.; Connelly, K.A. First report of hypersensitivity to ticagrelor. Can. J. Cardiol., 2014, 957, e3-e4.
[51]
Maybrook, R.J.; Fischer, R.; Deibert, B.; Gillihan, R.; Laarman, R.; Fraga, G.; Aires, D.; Gollub, S. Ticagrelor-induced acute generalized exanthematous pustulosis. Int. J. Cardiol., 2015, 191, 11-12.
[52]
Dai, J.; Lyu, S.; Ge, C. Hypersensitivity to ticagrelor and low response to clopidogrel: A case report. Asia Pac. Allergy, 2017, 7, 51-53.
[53]
Peppard, S.R.; Held-Googluck, B.; Beddingfield, R. Use of prasugrel in a patient with clopidigrel hypersensitivity. Ann. Pharmacother., 2011, 45, e54.
[54]
Norgard, N.B.; DiNicolantonio, J.J. Clopidogrel, prasugrel, or ticagrelor? A practical guide to use of antiplatelet agents in patients with acute coronary syndromes. Postgrad. Med., 2013, 125, 91-102.
[55]
Angiolillo, D.J.; Rollini, F. Switching from prasugrel to clopidogrel: Navigating in unknown waters. JACC Cardiovasc. Interv., 2013, 6, 166-168.
[56]
Chemnitz, J.; Sohngen, D.; Schulz, A.; Diehl, V.; Scheid, C. Fatal toxic bone marrow failure associated with clopidogrel. Eur. J. Haematol., 2003, 71, 473-474.
[57]
Mallet, L.; Mallet, J. Ticlopidine and fatal aplastic anemia in an elderly woman. Ann. Pharmacother., 1994, 28, 1169-1671.
[58]
Jacob, S.; Dunn, B.L.; Qureshi, Z.P.; Bandarenko, N.; Kwaan, H.C.; Pandey, D.K.; McKoy, J.M.; Barnato, S.E.; Winters, J.L.; Cursio, J.F.; Weiss, I.; Raife, T.J.; Carey, P.M.; Sarode, R.; Kiss, J.E.; Danielson, C.; Ortel, T.L.; Clark, W.F.; Rock, G.; Matsumoto, M.; Fujimura, Y.; Zheng, X.L.; Chen, H.; Chen, F.; Armstrong, J.M.; Raisch, D.W.; Bennett, C.L. Ticlopidine-, clopidogrel-, and prasugrel-associated thrombotic thrombocytopenic purpura: A 20-year review from the Southern Network on Adverse Reactions (SONAR). Semin. Thromb. Hemost., 2012, 38, 845-853.
[59]
Shah, R. Keough, L.A.; Belalcazar-Portacio, A.; Ramanathan, K.B. Ticagrelor as an alternative in clopidogrel-associated neutropenia. Platelets, 2015, 26, 80-82.
[60]
Beavers, C.J.; Carris, N.W.; Ruf, K.M. Management strategies for clopidogrel hypersensitivity. Drugs, 2015, 75, 999-1007.
[61]
Montalto, M.; Porto, I.; Gallo, A.; Camaioni, C.; Bona, R.D.; Grieco, A.; Crea, F.; Landolfi, R. Clopidogrel-induced neutropenia after coronary stenting: is cilostazol a good alternative? Int. J. Vasc. Med., 2011, 2011, 867964.
[62]
Lee, S.W. 1; Park, S.W.; Kim, Y.H.; Yun, S.C.; Park, D.W.; Lee, C.W.; Kang, S.J.; Park, S.J.; Lee, J.H.; Choi, S.W.; Seong, I.W.; Lee, N.H.; Cho, Y.H.; Shin, W.Y.; Lee, S.J.; Lee, S.W.; Hyon, M.S.; Bang, D.W.; Choi, Y.J.; Kim, H.S.; Lee, B.K.; Lee, K.; Park, H.K.; Park, C.B.; Lee, S.G.; Kim, M.K.; Park, K.H.; Park, W.J. Declare-long ii study investigators. A randomized, double-blind, multicenter comparison study of triple antiplatelet therapy with dual antiplatelet therapy to reduce restenosis after drug-eluting stent implantation in long coronary lesions: Results from the declare-long ii (drug-eluting stenting followed by cilostazol treatment reduces late restenosis in patients with long coronary lesions) trial. J. Am. Coll. Cardiol., 2011, 157, 1264-1270.
[63]
Lee, S.W.; Chun, K.J.; Park, S.W.; Kim, H.S.; Kim, Y.H.; Yun, S.C.; Kim, W.J.; Lee, J.Y.; Park, D.W.; Lee, C.W.; Hong, M.K.; Rhee, K.S.; Chae, J.K.; Ko, J.K.; Park, J.H.; Lee, J.H.; Choi, S.W.; Jeong, J.O.; Seong, I.W.; Jon, S.; Cho, Y.H.; Lee, N.H.; Kim, J.H.; Park, S.J. Comparison of triple antiplatelet therapy and dual antiplatelet therapy in patients at high risk of restenosis after drug-eluting stent implantation (from the declare-diabetes and -long trials). Am. J. Cardiol., 2010, 105, 168-173.
[64]
Cannon, C.P.; Gropper, S.; Bhatt, D.L.; Ellis, S.G.; Kimura, T.; Lip, G.Y.; Steg, P.G.; Ten Berg, J.M.; Manassie, J.; Kreuzer, J.; Blatchford, J.; Massaro, J.M.; Brueckmann, M.; Ferreiros Ripoll, E.; Oldgren, J. Hohnloser, S.H. design and rationale of the re-dual pci trial: a prospective, randomized, phase 3b study comparing the safety and efficacy of dual antithrombotic therapy with dabigatran etexilate versus warfarin triple therapy in patients with nonvalvular atrial fibrillation who have undergone percutaneous coronary intervention with stenting. Clin. Cardiol., 2016, 39, 555-564.
[65]
Kim, G.W.; Kang, S.Y.; Sohn, K.H.; Kim, S.H.; Cho, S.H.; Min, K.U.; Chang, Y.S. Successful sequential desensitization in a patient with drug hypersensitivity to three kinds of antiplatelet agents. Allergy Asthma Respir. Dis., 2016, 4, 374-377.
Related Journals
Current Diabetes Reviews
Current Medicinal Chemistry
Current Pharmaceutical Design
Current Topics in Medicinal Chemistry
Current Respiratory Medicine Reviews
Infectious Disorders - Drug Targets
Anti-Infective Agents
Coronaviruses
Recent Advances in Inflammation & Allergy Drug Discovery
Current Probiotics
Related Books
Mitochondrial DNA and the Immuno-inflammatory Response: New Frontiers to Control Specific Microbial Diseases
Pharmacological and Molecular Perspectives on Diabetes
Frontiers in Clinical Drug Research – Anti Allergy Agents
Frontiers in Clinical Drug Research-Diabetes and Obesity
Frontiers in Inflammation
Frontiers in Clinical Drug Research-Diabetes and Obesity
Article Metrics
31
2