Characterization of Clopidogrel Hypersensitivity Reactions and Management With Oral Steroids Without Clopidogrel Discontinuation

Study Questions:

What is clopidogrel hypersensitivity, and how can it be managed successfully with oral steroids without clopidogrel discontinuation?


Patients diagnosed with clopidogrel hypersensitivity after percutaneous coronary intervention (PCI) underwent evaluation and received oral prednisone without clopidogrel discontinuation. Cutaneous testing was performed after completion of clopidogrel therapy for diagnosis and assessment of cross-reactivity. Clopidogrel hypersensitivity onset time was compared across presentation type (generalized rash, focal rash, or angioedema/urticaria) with the Kruskal-Wallis test and between the two loading dose (300 mg and 600 mg) groups with the Wilcoxon rank-sum test. Leukocyte, neutrophil, lymphocyte, eosinophil, and platelet counts at baseline, 1 day after PCI, and at clopidogrel hypersensitivity onset were analyzed with repeated-measures analysis of variance; Bonferroni correction was applied for multiple comparisons.


Sixty-two patients representing 1.6% of the PCI population developed clopidogrel hypersensitivity during the study period. The mean age was 62 ± 11 years, 71% of patients were male, and 35% reported prior adverse drug reaction. Clopidogrel hypersensitivity manifested as generalized exanthema in 79%, localized skin reaction in 16%, and angioedema or urticaria in 5% of patients. Biopsy of affected areas demonstrated alymphocyte-mediated delayed hypersensitivity reaction. Complete resolution of hypersensitivity reaction was observed in 61 patients (98%) with a short course of oral prednisone. Cutaneous testing confirmed delayed hypersensitivity reaction to clopidogrel in 34 (81%) and immediate hypersensitivity in 3 of 42 patients (7%) tested. Allergenic crossreactivity was observed for ticlopidine in 10 (24%), prasugrel in 7 (17%), and both ticlopidine and prasugrel in 3 patients (7%). Histological examination showed lymphocyte-mediated hypersensitivity in abnormal patch test areas.


The authors concluded that clopidogrel hypersensitivity can be managed with oral steroids without clopidogrel discontinuation.


The study reports that clopidogrel hypersensitivity in most patients was characterized by a generalized exanthematous rash affecting the trunk and proximal extremities a median of 5 days after clopidogrel initiation, and both generalized and focal types of clopidogrel hypersensitivity can be successfully treated with a short course of oral steroids without discontinuation of clopidogrel, regardless of the type of immunologic response. Furthermore, a significant number of patients (40%) with an allergic cutaneous response to clopidogrel showed allergenic cross-reactivity with ticlopidine or prasugrel. Ticagrelor may be a potential therapeutic option in some patients with persistent reactions, but needs further study.

Clinical Topics: Invasive Cardiovascular Angiography and Intervention

Keywords: Patch Tests, Platelet Aggregation Inhibitors, Drug-Related Side Effects and Adverse Reactions, Biopsy, Thiophenes, Urticaria, Piperazines, Angioplasty, Skin Tests, Lymphocytes, Cardiology, Hypersensitivity, Exanthema

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