Frequency of Allergy to Ticlopidine Among Patients Allergic to Clopidogrel and Vice Versa

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Frequency of Allergy to Ticlopidine Among
Patients Allergic to Clopidogrel (and Vice Versa)
GEISINGER

• Juzar Lokhandwala MD, RVT Patricia Best MD,
  FACC Kristina Evans MPH, Peter B. Berger MD,
  FACC
• Geisinger Medical Center, Danville, PA, Mayo
  Clinic, Rochester, MN

Acknowledgements Kristina Evans, MA Nina
Bastian, BS for assistance in querying the
electronic health records at Geisinger Clinic,
and Yvette Henry, PhD, for editorial assistance.
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Background
GEISINGER

• Clopidogrel and ticlopidine are the only 2
  antiplatelet agents of the thienopyridine class.
• Dual antiplatelet therapy (aspirin and a
  thienopyridine) improves outcome in pts who
  receive coronary stents and have acute coronary
  syndromes.
• Recent data suggesting an increased risk of late
  thrombosis of drug eluting stents has lead to
  guidelines recommending dual antiplatelet therapy
  for at least 1 year.

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Background
GEISINGER

• Ticlopidine causes nausea/vomiting/diarrhea in
  in similar efficacy but fewer side effects, has
  replaced ticlopidine.
• However, allergic or adverse hematologic
  reactions occur in 1 of pts taking clopidogrel.
• Premature discontinuation of clopidogrel is a
  strong predictor of stent thrombosis.
• Switching to ticlopidine immediately is the most
  commonly chosen and most evidence based option in
  pts with a severe allergic reaction to
  clopidogrel.

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GEISINGER
Structural similarity between ticlopidine and
clopidogrel.

• No common metabolites of the two thienopyridines
  have yet been found.

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Background
GEISINGER

• Several case reports of patients allergic to both
  clopidogrel and ticlopidine have been described.
• However, the frequency of cross reactivity of
  developing an allergic or adverse hematologic
  reaction to ticlopidine in pts with similar
  reaction to clopidogrel (and vice versa) is
  unknown.
• It is also unknown if the reaction to the second
  thienopyridine is life-threatening.

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Objective
GEISINGER

• To determine the likelihood of an allergic or
  hematological adverse reaction to ticlopidine in
  pts with an allergic or hematological adverse
  reaction to clopidogrel (and vice versa).
• In pts with an allergic or hematological adverse
  reaction to the 2nd thienopyridine, to determine
  if the reaction was life threatening.

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Methods
GEISINGER

• Study type Retrospective chart review
• We analyzed the electronic health record at
  Geisinger and Mayo Clinic.
• Inclusion Criteria
• Age 18 years
• Allergic (rash, angioedema, anaphylaxis) or
  hematologic adverse reaction to either
  thienopyridine between January 1995 and June 2007
• Received the alternative thienopyridine.
• The time course of the development and resolution
  of the adverse reaction had to suggest that the
  thienopyridine was the most likely cause.

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Methods
GEISINGER

• Exclusion Criteria
• Patients who had voluntarily opted not to be
  included in any research study or who had not
  given research authorization for the use of their
  medical records were excluded, as required by
  Minnesota law.
• Note- Intolerance due to gastrointestinal side
  effects, bleeding and bruising were not
  considered to represent an allergic reaction.

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Methods
GEISINGER

• Data from both Geisinger and Mayo were analyzed
  together.
• Patients were assigned to 1 of these 3 groups
• pts allergic to both thienopyridines
• pts allergic to clopidogrel who tolerated
  ticlopidine
• pts allergic to ticlopidine who tolerated
  clopidogrel.
• Data are presented as means and percentages with
  confidence intervals.

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Results
GEISINGER

• Seventy-six pts with an allergy or
  hematologic adverse reaction to clopidogrel
  (n52) or ticlopidine (n38) were identified who
  had also received the other thienopyridine.

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GEISINGER
The Study Population
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GEISINGER
Baseline clinical characteristics of pts in the
study (n76)
HEAL. TEACH. DISCOVER. SERVE.
13
GEISINGER
14
GEISINGER

• No pts with TTP were included in the study

15
GEISINGER
(18 95 CI 11- 29)
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Severity of the allergic or adverse reaction
GEISINGER

• In pts with an allergic or adverse hematologic
  reaction to one thienopyridine, an allergic or
  adverse hematologic reaction to the alternative
  thienopyridine was never life threatening.
• In one patient with angioedema due to
  clopidogrel, recurrent angioedema of lesser
  severity developed after exposure to ticlopidine.
  
• In 2 pts who developed thrombocytopenia with
  clopidogrel, recurrence of thrombocytopenia was
  seen with ticlopidine.
• None of the pts required hospital admission or
  emergency therapy.

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Study limitations
GEISINGER

• Retrospective study
• It is possible that pts may have developed
  allergic or hematologic reactions to a
  thienopyridine and received care somewhere other
  than Geisinger or Mayo Clinic, in which case the
  observed frequency of adverse reactions reported
  in this study may be an underestimate.

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Conclusion
GEISINGER

• Pts with an allergic or adverse hematologic
  reaction to a thienopyridine who are administered
  the other thienopyridine have an 18 increased
  risk of an allergic or hematologic adverse
  reaction to the 2nd thienopyridine.
• In pts who develop what is believed to be an
  allergic (mostly rash) or adverse hematologic
  reaction to the 2nd thienopyridine, the reaction
  was not life threatening in any pt.