Clopidogrel Hypersensitivity Treated With Steroids a Success

September 29, 2011

September 29, 2011 (Toronto, Ontario)Clopidogrel hypersensitivity can be successfully treated with a single three-week course of prednisone without needing to interrupt treatment with the antiplatelet agent, a new study has confirmed [1].

The study, published in the September 27, 2011 issue of the Journal of the American College of Cardiology, was conducted by a group led by Dr Asim Cheema (St Michael's Hospital, Toronto, ON).

Cheema commented to heartwire : "There have been a couple of smaller studies suggesting that a course of steroids can successfully treat clopidogrel hypersensitivity, but this is the largest and most comprehensive experience so far on this topic. We have also been able to characterize the effect as a delayed sensitivity reaction. This means it normally takes a few days to occur. This is quite unusual with drug reactions, which normally exert themselves much sooner than this."

Cheema explained that hypersensitivity to clopidogrel can occur in up to 5% of patients and usually manifests itself as a skin rash. He added that it is important for doctors to realize that the reaction generally takes a few days to appear, as this can make it difficult to establish a definite cause.

The researchers showed that the hypersensitivity disappeared in all but one of 62 patients with a three-week course of prednisone. And clopidogrel could be continued throughout treatment.

"Great News"

Cheema noted that the most common way of dealing with this hypersensitivity at the moment is to stop the clopidogrel or switch patients to a different antiplatelet agent. But this puts them at risk of events, and some patients also react to other agents. "We have shown that stopping clopidogrel is unnecessary. This is great news, as alternative agents are more expensive and are not approved for as many indications as clopidogrel," he commented.

Cheema said the three-week steroid course was well tolerated. "There are no long-term effects of taking steroids for just a few weeks. You have to be careful with diabetics, though, as steroids can cause glucose control to become impaired."

The study also established that the allergic reaction can be either generalized--an extensive rash all over the body--or focal--occurring in just one or two locations. In this study, the rash was generalized in 79% of patients and focal in about 16%, with the remaining 5% experiencing angioedema or urticaria.

In the paper, the authors report that they identified 62 patients in their practice with hypersensitivity reactions attributable to clopidogrel, representing 1.6% of the patient population undergoing PCI during the study period. Of these, 35% reported experiencing adverse drug reactions previously.

Prednisone was started at 30 mg twice a day, with the dose being gradually reduced over a three-week period. This was associated with a complete resolution of the hypersensitivity reaction in 61 patients (98%). Cutaneous testing confirmed delayed hypersensitivity reaction to clopidogrel in 34 (81%) and immediate hypersensitivity in three of 42 patients (7%) tested.

Cell-Mediated Immune Reaction

The researchers performed patch tests to understand the pathophysiology behind the reaction and found that it was caused by a cell-mediated immunity.

Cheema explained to heartwire that cell-mediated reactions like this one take time to develop, whereas an antibody-mediated reaction shows itself much faster. Also, as clopidogrel hypersensitivity is cell-mediated, it will occur the first time a patient takes the drug, whereas if a reaction is antibody-mediated, it sometimes does not occur the first time the drug is given, as this is when the body becomes sensitized, and the reaction manifests itself only the next time the drug is taken.

"The prednisone is causing an immune tolerance. The reaction does not disappear permanently, but the patient develops tolerance to it. If the patient stops clopidogrel and then is rechallenged, the reaction will occur again."

The researchers also used skin-patch testing to gauge response to prasugrel and ticlopidine, and they found that 17% of patients who were hypersensitive to clopidogrel were also allergic to prasugrel, 24% were also allergic to ticlopidine, and 7% were allergic to all three agents. They didn't test ticagrelor as it wasn't available at the time.

In an accompanying editorial [2], Drs Paul Gurbel, Young-Hoon Jeong, and Udaya Tantry (Sinai Center for Thrombosis Research, Baltimore, MD) say this report is "the single most comprehensive assessment of the mechanisms underlying clopidogrel hypersensitivity and its treatment."

They add that the findings "provide the clinician with reassurance that a simple treatment is safe and highly effective and that interruption of clopidogrel therapy is not required," which they say is "very good news for the troubled patient and worried physician."

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