Clopidogrel Hypersensitivity Research Articles

Use of Prasugrel in Patients with Clopidogrel Hypersensitivity

Allergic response to clopidogrel is a significant and difficult clinical problem as it is one of the recommended drugs after coronary stenting to prevent thrombosis. We present the case of a 57-year-old man who underwent coronary revascularization and developed an urticarial rash after being started on dual antiplatelet medication (aspirin and clopidogrel). He was managed conservatively, to which he responded well and was discharged on prasugrel. This case study from India adds to the available literature and discusses the alternative drugs that could be used in patients with clopidogrel hypersensitivity.

Treatment of Clopidogrel Hypersensitivity: The Jefferson Approach

Despite the advent of newer antiplatelet therapies, clopidogrel remains the mainstay of treatment for patients with cardiovascular disease, especially those who undergo coronary stent implantation. Hypersensitivity reactions to clopidogrel that develop soon after stenting present a significant clinical challenge. The widespread use of clopidogrel in the management of patients with coronary artery disease necessitates awareness of treatment options in the setting of an allergic reaction. It has been demonstrated that clopidogrel hypersensitivity can be successfully managed without interrupting clopidogrel therapy. We review available treatment options and highlight the treating-through approach developed at our institution.

Clopidogrel Hypersensitivity: Pathogenesis, Presentation and Diagnosis.

This paper provides an overview of the pathogenesis, presentation and diagnosis of clopidogrel hypersensitivity. The majority of clopidogrel hypersensitivity cases are due to a T cell mediated Gell and Coombs Type IV reaction. History, histology, and patch testing have shown consistency with a T cell mediated mechanism. Clopidogrel reactions most commonly present as a mild delayed maculopapular erythematous rash 5 to 10 days after introduction of the drug, and do not always require discontinuation of the drug. Severe cutaneous, systemic, and immediate adverse reactions to clopidogrel are rare. For the diagnosis of clopidogrel hypersensitivity, drug causality can be determined using patch testing, or for mild reactions, recurrence of symptoms after drug reintroduction, although neither are required for diagnosis.

Managing Clopidogrel Hypersensitivity without Interrupting Therapy: The Toronto Approach.

Clopidogrel remains a widely used antiplatelet agent for patients with established or high risk of atherothrombotic disease, particularly those treated with coronary, carotid or peripheral endovascular stenting. Clopidogrel hypersensitivity is an uncommon but well established adverse drug reaction presenting a challenge for patient management. The clinical presentation ranges from focal or diffuse cutaneous manifestations in most patients to angioedema in some and a systemic immune response in rare cases. The treatment options include drug discontinuation with or without desensitization therapy, switching to alternate ADP receptor antagonists or administration of oral steroids while continuing clopidogrel in patients at high risk of adverse events with clopidogrel discontinuation. In this review the author describes the phenomenon of clopidogrel hypersensitivity, various treatment strategies.

Use of Alternative Antiplatelet Agents for Clopidogrel Hypersensitivity.

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.

P2.4 - Pharmacoeconomic Analysis of Antithrombotic Treatment In Coronary Artery Disease (Cad) Patients With Clopidogrel Hypersensitivity After Percutaneous Coronary Intervention (Pci)

P2.4 - Pharmacoeconomic Analysis of Antithrombotic Treatment In Coronary Artery Disease (Cad) Patients With Clopidogrel Hypersensitivity After Percutaneous Coronary Intervention (Pci)

Erratum to: Management Strategies for Clopidogrel Hypersensitivity.

Erratum to: Management Strategies for Clopidogrel Hypersensitivity.

Work up for the clopidogrel hypersensitivity that led to recognising the undiagnosed myelodysplastic syndrome.

Work up for the clopidogrel hypersensitivity that led to recognising the undiagnosed myelodysplastic syndrome.

Strategies for managing clopidogrel hypersensitivity should take patient-specific factors into account

Approximately 4 % of patients receiving clopidogrel develop hypersensitivity reactions, potentially limiting the use of this treatment. Managing clopidogrel hypersensitivity can be challenging and requires consideration of patient-specific factors. Management options include avoiding clopidogrel use, overcoming the clopidogrel reaction, and switching to an alternative antiplatelet agent.

Pharmacoeconomic analysis comparing Clopidogrel Desensitization Protocol versus ticagrelor for Antithrombotic treatment in Coronary Artery Disease Patients with Clopidogrel Hypersensitivity after PCI

Pharmacoeconomic analysis comparing Clopidogrel Desensitization Protocol versus ticagrelor for Antithrombotic treatment in Coronary Artery Disease Patients with Clopidogrel Hypersensitivity after PCI

Management Strategies for Clopidogrel Hypersensitivity.

Clopidogrel is a cornerstone of dual antiplatelet therapy. Hypersensitivity reactions potentially limit the use of this treatment and present a significant clinical challenge. The authors have developed recommendations for the management of clopidogrel hypersensitivity with consideration for the etiology, pathophysiology, and critical evaluation of potential management strategies. The clopidogrel hypersensitivity reaction is complex in mechanism and presents generally around day 5 of treatment. Generalized reactions are most common, but the reaction may also be localized or systemic. Screening patients for hypersensitivity is not always possible because the type IV delayed reaction is not detected reliably by conventional skin prick, intradermal challenge, or patch testing. Proposed strategies for management of clopidogrel hypersensitivity include treatment of the reaction with corticosteroids, clopidogrel desensitization, substituting an alternative P2Y12 inhibitor, or clopidogrel avoidance. The safety, efficacy, and cost of each potential strategy must be considered when managing a patient with clopidogrel hypersensitivity.

P1105 : Immunologic basis of clopidogrel hypersensitivity and detection by Lymphocyte Toxicity Assay

P1105 : Immunologic basis of clopidogrel hypersensitivity and detection by Lymphocyte Toxicity Assay

TCT-484 Immunologic Basis of Clopidogrel Hypersensitivity and Diagnosis by Lymphocyte Toxicity Assay

Clopidogrel hypersensitivity(HS)manifesting is a recognized complication affecting ∼3% of treated patients. Contrary to other drug allergy, the immunologic basis of clopidogrel HS are poorly understood. In this report, we characterize the cellular and immunologic mechanism of clopidogrel HS and

Ticagrelor Use in a Patient With a Documented Clopidogrel Hypersensitivity.

To report the use of ticagrelor in a patient with a documented hypersensitivity reaction to clopidogrel. A 64-year-old woman presented with non-ST-segment elevation myocardial infarction (NSTEMI) with a history significant for a hypersensitivity reaction to clopidogrel and was medically managed. Based on the patient's past medical history and current evidence available, the determination was made to use ticagrelor in this patient. Ticagrelor was administered without reaction during the hospital stay and on assessment at 2 and 4 weeks postdischarge. Hypersensitivity occurs in approximately 1% of patients receiving clopidogrel. Although the risk of hypersensitivity reaction to clopidogrel is low, evidence to support alternative antiplatelets in this setting is relatively limited. Prasugrel has a similar structure to clopidogrel and, therefore, may cross-react. Furthermore, prasugrel is not recommended in the medical management of NSTEMI. Ticagrelor is a newer P2Y12 inhibitor that contains a cyclopentyltriazolopyrimidine structure. Because of the difference in structure, a lower theoretical risk of cross-reactivity with the thienopyridines would be anticipated. However, there are no reports to date that investigate the use of this agent in patients with a documented thienopyridine allergy. The current case report describes the use of ticagrelor in a patient with documented hypersensitivity to clopidogrel. In this patient, ticagrelor was well tolerated during hospital admission and at 2 and 4 weeks postdischarge following administration.

Circulation: Clinical Summaries

<i>Circulation:</i> Clinical Summaries

A RARE CASE OF CLOPIDOGREL HYPERSENSITIVITY COMBINATION WITH UPPER GASTROINTESTINAL BLEEDING

ObjectivesWe describe a patient who developed upper gastrointestinal bleeding complicating with clopidogrel hypersensitivity 1 week after he had started taking clopidogrel following coronary stent implantation.MethodsHe was treated with antihistamines and...

287 Immunological Mechanisms and Histologic Characteristics of Clopidogrel Induced Cutaneous Hypersensitivity

287 Immunological Mechanisms and Histologic Characteristics of Clopidogrel Induced Cutaneous Hypersensitivity

Use of Prasugrel in a Patient with Clopidogrel Hypersensitivity

To report a case of successful use of prasugrel following percutaneous coronary intervention with placement of a bare metal stent in a patient with a documented hypersensitivity reaction to clopidogrel. A 61-year-old male with a history of coronary artery disease with coronary stent placement presented with ST-elevation myocardial infarction. The patient had developed Stephens-Johnson syndrome 6 years earlier following clopidogrel administration, characterized by erythematous plaques and subsequent desquamation of the hands and feet; clopidogrel was discontinued and he was subsequently treated with ticlopidine in addition to aspirin. The third-generation thienopyridine prasugrel was initiated as a therapeutic alternative to clopidogrel after placement of a bare metal stent; a 60-mg dose was administered after extubation, followed by 10 mg/day. No signs of allergic reaction were observed in the days, weeks, and months following administration. Thienopyridines, specifically clopidogrel, are the standard of care for prevention of coronary stent thrombosis; however, there are few data available on cross-hypersensitivity between these agents. One study demonstrated that 27% of patients who developed an allergic or hematologic reaction to clopidogrel developed a similar reaction to ticlopidine. Other therapeutic options for patients with clopidogrel hypersensitivity who are undergoing a percutaneous coronary intervention with stent placement include clopidogrel desensitization, warfarin plus aspirin, cilostazol, ticagrelor, and ticlopidine. However, these options are limited by efficacy and/or toxicity. With its approval in 2009, prasugrel has become a potential treatment option. Prasugrel may be considered a therapeutic alternative in some patients allergic or intolerant to clopidogrel, but additional data are warranted to make a strong conclusion.

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

The purpose of this study was to characterize clopidogrel hypersensitivity and describe its successful management with oral steroids without clopidogrel discontinuation. Hypersensitivity reactions to clopidogrel are poorly understood and present difficulty in management. Patients diagnosed with clopidogrel hypersensitivity after percutaneous coronary intervention 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. Sixty-two patients representing 1.6% of the percutaneous coronary intervention 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 a lymphocyte-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 cross-reactivity 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. Clopidogrel hypersensitivity is manifested as generalized exanthema and is caused by a lymphocyte-mediated delayed hypersensitivity in most patients. This can be managed with oral steroids without clopidogrel discontinuation. Allergenic cross-reactivity with ticlopidine, prasugrel, or both is present in a significant number of patients with clopidogrel hypersensitivity.

Management of Clopidogrel Hypersensitivity Without Drug Interruption

Clopidogrel hypersensitivity affects up to 6% of treated patients, often leading to discontinuation of the drug. Conventional desensitization protocols incorporate a washout period off medication that may be problematic after percutaneous coronary intervention because premature discontinuation of dual antiplatelet therapy is a major risk factor for stent thrombosis. The purpose of this study was to evaluate a strategy for treating clopidogrel hypersensitivity without drug interruption using corticosteroids and antihistamines to facilitate development of physiologic tolerance. The study population consisted of 25 consecutive patients who developed clopidogrel hypersensitivity after percutaneous coronary intervention and were managed with suppressive therapy using corticosteroids and antihistamines. Treatment success (resolution of hypersensitivity symptoms without interrupting clopidogrel) was assessed, in addition to duration of clopidogrel therapy and adverse cardiac events during late follow-up (mean 670 ± 630 days). The cohort included 19 men and 6 women with a mean age of 62 ± 9 years. Drug-eluting stents were used in 16 patients (64%). Clopidogrel hypersensitivity occurred 6 ± 2 days after drug initiation. Treatment included corticosteroids (5 patients), antihistamines (5 patients), or corticosteroids and antihistamines (15 patients). Patients treated with corticosteroids received tapering courses for a mean of 10 ± 8 days. Treatment was successful with sustained symptom resolution in 22 of 25 patients (88%). Clopidogrel therapy was continued in successfully desensitized patients for 417 ± 369 days and in patients with drug-eluting stents for 529 ± 376 days. There were no deaths, myocardial infarctions, or stent thrombosis during extended follow-up. In conclusion, clopidogrel hypersensitivity can be successfully treated using short-course corticosteroids and antihistamines without interrupting drug therapy. This technique enables long-term continuation of clopidogrel and confers a low risk of adverse cardiac events.