Ryan T. Kammer, PharmD
Published: 07/15/2009
Abstract and Introduction
Abstract
A 55-year-old male was admitted with a recent non-ST-elevation myocardial infarction (NTEMI) and taken to the catheterization laboratory for further management. Culprit lesions were identified in the distal right coronary artery and ramus intermedius, requiring 2 paclitaxel-eluting stents (Taxus®, Boston Scientific Corp., Natick, Massachusetts) and a bare-metal stent, respectively. The patient was started on ticlopidine therapy due to a history of clopidogrel-associated skin rash. One day after ticlopidine initiation, the patient developed pruritus and a maculopapular rash of the trunk area. The patient was discharged briefly on aspirin and cilostazol therapy with readmission plans for clopidogrel desensitization. A modified protocol was successfully utilized to desensitize the patient.
Introduction
Thienopyridine therapy is a necessity after implantation of a drug-eluting stent (DES). Recent guidelines2 mandate a minimum of 12 months of thienopyridine therapy in an attempt to prevent late stent thrombosis, a devastating and possibly fatal complication associated with DES. Rarely, patients develop a rash from clopidogrel that requires discontinuation of the drug. Desensitization is an option because clopidogrel skin reactions are thought to involve an Ig-E-mediated component.[1] Successful densensitization has been reported in the immunology,[1,3] cardiology,[4-6] and recently, in the pharmacy literature.[7] It is important to continue to report strategies for desensitization to a therapy that is imperative after coronary artery stenting, especially in those patients who react to both currently available thienopyridine derivatives.
Case Presentation
This case describes a 55-year-old male transferred to our facility for coronary angiography following a NSTEMI. His history revealed prior DES implantation in the right coronary artery (RCA) following an inferior-wall myocardial infarction and documented clopidogrel intolerance due to rash. Catheterization revealed a patent stent, but significant lesions in the distal RCA and ramus intermedius (RI). The decision was made to proceed with percutaneous intervention, which involved implantation of 2 DES in the RCA and a bare-metal stent (BMS) in the RI lesion. The planned antiplatelet regimen post procedure was aspirin and ticlopidine. However, after ticlopidine initiation, the patient developed significant pruritus and a maculopapular rash of the trunk region. The rash resolved following ticlopidine discontinuation and intravenous administration of a dose of methylprednisolone and diphenhydramine. A consulting immunologist recommended a clopidogrel desensitization protocol. Thus, the patient was briefly discharged on aspirin and cilostazol with readmission plans for desensitization in the cardiac intensive care unit. He was successfully desensitized 4 days later using a modified protocol from Lee-Wong M et al1 (Table 1).
Table 1. Oral Desensitization Protocol
The protocol involves an escalating regimen of 15 doses administered orally in 30-minute intervals over a 7-hour period. The patient is continuously monitored, and an anaphylaxis regimen consisting of antihistamines and epinephrine is readily available. A 4-day course of corticosteroids may prevent recurrent or protracted anaphylactic reactions that occur in up to 20% of patients.8 If a minor reaction such as hives develops, an antihistamine is administered and the offending dose is repeated in 30 minutes. Once tolerated, the dose escalation schedule proceeds. In this case, doses were compounded in the pharmacy, with protocol modification of dose 13 to 18.75 mg = 1/4 tablet (from 20 mg), and dose 14 to 37.5 mg = 1/2 tablet (from 40 mg). This patient tolerated the entire protocol without evidence of a reaction and was discharged home the following day. The patient was extensively counseled on the risk of resensitization if subsequent clopidogrel doses were missed.
Discussion
Thienopyridine therapy is mandated after DES implantation. Unfortunately, when challenged with clopidogrel allergy or intolerance, options are limited, but include ticlopidine therapy, a cilostazol regimen or clopidogrel desensitization.
Despite potential blood dyscrasias, many clinicians initially attempt ticlopidine therapy. Unfortunately, the cross-sensitivity rate between clopidogrel and ticlopidine is unknown and occurrences are only described in case reports[7] such as this one. This patient reacted to both drugs whose chemical structure differs only by a carboxymethyl side chain added to clopidogrel.[5] The use of cilostazol after DES deployment has been described in the literature,[9,10] but heart failure often prohibits its use. Ultimately, clopidogrel desensitization may be required, thus reports of success and failure with published protocols must continue to be circulated.
Conclusion
This is a case of successful clopidogrel desensitization after coronary intervention involving DES implantation in a patient allergic to both clopidogrel and ticlopidine. At 15-month follow up, the patient remains on clopidogrel therapy with patent stents.
References
- Lee-Wong M, Gadhvi, D, Resnick D. Clopidogrel desensitization. Ann Allergy Asthma Immunol 2006;96:756-757.
- Anderson JL, Adams CD, Antman EM, et al. ACC/AHA 2007 Guidelines for the management of patients with unstable angina/Non-ST-elevation myocardial infarction: Executive summary. Circulation 2007;116:803-877.
- Vigo PG, MacDowell AL, Wedner HJ. Successful desensitization with clopidogrel after a positive skin test. Ann Allergy Asthma Immunol 2005;94:132.
- Camara MG, Almeda FQ. Clopidogrel (Plavix) desensitization: A case series. Catheter Cardiovasc Interv 2005;65:525-527.
- Walker NE, Fasano MB, Horwitz PA. Desensitization for the management of clopidogrel hypersensitivity: Initial clinical experience. J Invasive Cardiol 2006;18:341-344.
- Von Tiehl KF, Price MJ, Valencia R, et al. Clopidogrel desensitization after drug-eluting stent placement. J Am Coll Cardiol 2007;50:2039-2043.
- Owen P, Garner J, Hergott L, Page II RL. Clopidogrel desensitization: Case report and review of published protocols. Pharmacotherapy 2008;28:259-270.
- Lieberman P. Biphasic anaphylactic reactions. Ann Allergy Asthma Immunol 2005;95:217.
- Makkar K, Wilensky RL, Julien MB, et al. Rash with both clopidogrel and ticlopidine in two patients following percutaneous coronary intervention with drug-eluting stents. Ann Pharmacother 2006;40:1204-1207.
- Park SJ, Shim WH, Ho DS, et al. A paclitaxel-eluting stent for the prevention of coronary restenosis. N Engl J Med 2003;348:1537-1545.
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