Background
Clopidogrel is sometimes substituted for ticlopidine when cerebrovascular or cardiovascular
patients develop hematologic abnormalities after ticlopidine treatment. However, the
adverse event rate after the substitution to clopidogrel remains undetermined. Therefore,
in this study, we aimed to define the risk of adverse events after substituting clopidogrel
for ticlopidine without a washout period.
Methods
We prospectively enrolled patients older than 20 years who had a history of noncardioembolic
strokes, including transient ischemic attacks, were treated with ticlopidine for at
least 6 months. This study was conducted from August 26, 2008, when the first patient
was enrolled, to January 16, 2012, the date of the last patient examination, at 8
active stroke centers in Hiroshima, Japan. We excluded patients who had severe disabilities,
evidence of cardioembolic stroke, or history of a bleeding event. Each patient received
clopidogrel (either 50 mg or 75 mg) once a day in place of ticlopidine without a washout
period. Follow-up exams were scheduled within 12 months after the medication substitution.
The primary end point of this study was adverse events of interest, including clinically
significant reduced blood cell counts, hepatic dysfunction, bleeding, and other serious
side effects.
Results
In this study, 110 patients were enrolled and analyzed in an intent-to-treat manner
(modified intent to treat). Within the scheduled follow-up periods, 9 primary end
point events were observed in separate patients. The primary end point events were
observed at a rate of 8.4% per year (Kaplan–Meier method). At the time of enrolment,
16 patients met the exclusion criteria, of which 8 recovered from their abnormal hematologic
results to the institutional normal limit after the substitution of ticlopidine for
clopidogrel (57.4% per year).
Conclusions
The adverse event rates after the substitution of ticlopidine for clopidogrel is similar
to the adverse event rates of patients who were initially treated with clopidogrel.
The substitution of clopidogrel for ticlopidine should be considered for patients
who develop hematologic abnormalities from ticlopidine treatment.
Key Words
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Article info
Publication history
Published online: February 21, 2014
Accepted:
December 16,
2013
Received in revised form:
December 9,
2013
Received:
November 25,
2013
Footnotes
This study was partially supported by Sanofi K.K., Tokyo, Japan.
Identification
DOI: https://doi.org/10.1016/j.jstrokecerebrovasdis.2013.12.025
Copyright
© 2014 National Stroke Association. Published by Elsevier Inc. All rights reserved.
