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.
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.
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).
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.
To read this article in full you will need to make a payment
Purchase one-time access:Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
One-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:Subscribe to Journal of Stroke and Cerebrovascular Diseases
Already a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
- Comparison of the European and Japanese guidelines for the management of ischemic stroke.Cerebrovasc Dis. 2013; 35: 402-418
- The efficacy and safety of ticlopidine and aspirin in non-whites: analysis of a patient subgroup from the Ticlopidine Aspirin Stroke Study.Neurology. 1993; 43: 27-31
- Patient characteristics in ticlopidine hydrochloride-induced liver injury: case-control study.Hepatol Res. 2005; 33: 234-240
- A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE).Lancet. 1996; 348: 1329-1339
- A randomized, double-blind study comparing the safety and efficacy of clopidogrel versus ticlopidine in Japanese patients with noncardioembolic cerebral infarction.Cerebrovasc Dis. 2008; 25: 40-49
- Clopidogrel trial in patients with elective percutaneous coronary intervention for stable angina and old myocardial infarction (CLEAN).Int Heart J. 2012; 53: 91-101
- Classification of subtype of acute ischemic stroke. Definitions for use in a multicenter clinical trial. TOAST. Trial of Org 10172 in Acute Stroke Treatment.Stroke. 1993; 24: 35-41
- Clopidogrel for Atherothrombotic Event Management in Patients with Peripheral Arterial Disease (COOPER) study: safety and efficacy of clopidogrel versus ticlopidine in Japanese patients.Ann Vasc Dis. 2012; 5: 364-375
- Clopidogrel two doses comparative 1-year assessment of safety and efficacy (COMPASS) study in Japanese patients with ischemic stroke.Cerebrovasc Dis. 2012; 34: 229-239
- Blood pressure levels and bleeding events during antithrombotic therapy: the Bleeding with Antithrombotic Therapy (BAT) Study.Stroke. 2010; 41: 1440-1444
- Effects of a perindopril-based blood pressure-lowering regimen on the risk of recurrent stroke according to stroke subtype and medical history: the PROGRESS trial.Stroke. 2004; 35: 116-121
- Dual antithrombotic therapy increases severe bleeding events in patients with stroke and cardiovascular disease: a prospective, multicenter, observational study.Stroke. 2008; 39: 1740-1745
Published online: February 21, 2014
Accepted: December 16, 2013
Received in revised form: December 9, 2013
Received: November 25, 2013
This study was partially supported by Sanofi K.K., Tokyo, Japan.
© 2014 National Stroke Association. Published by Elsevier Inc. All rights reserved.