Abstract
Two Phase III studies comparing the safety and efficacy of clopidogrel with ticlopidine as antiplatelet agents for the secondary prevention of vascular events in patients with prior stroke were performed in Japan. Both studies were randomized, double-blind, double-dummy comparative trials with the primary objective of comparing the clinical safety of treatment with either clopidogrel or ticlopidine for up to 12 months. The secondary objective was to assess the incidence of a combined efficacy endpoint of cerebral infarction, myocardial infarction, and vascular death. Patients with prior stroke were recruited during July 1996–February 1998 and September 2001–November 2003 at centers across Japan. The results of the two studies were combined in this analysis. There were 1,869 patients in the safety population (clopidogrel, 941; ticlopidine, 928). Significantly, fewer patients experienced a safety event in the clopidogrel group than in the ticlopidine group (p < 0.001; hazard ratio, 0.610; 95% confidence interval 0.529, 0.703). Almost twice as many patients in the ticlopidine group (25.6%) experienced hepatic dysfunction than in the clopidogrel group (13.4%). There were 1,862 patients evaluable for efficacy (clopidogrel, 939; ticlopidine, 923). There was no significant difference in the incidence of the combined efficacy endpoint between clopidogrel (2.6% of patients) and ticlopidine (2.5%). Clopidogrel was better tolerated than ticlopidine. There was no difference in the efficacy of the two agents with regard to the secondary prevention of vascular events in patients with prior stroke. This was the first combined analysis of direct comparison of clopidogrel with ticlopidine in the clinical setting.
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Acknowledgments
This research was supported by sanofi-aventis K.K. Editorial support was also provided by sanofi-aventis K.K. The authors would like to thank the following investigators from Japan who took part in the two clinical trials: Shinya Goto, Tokai University School of Medicine, Kanagawa; Syunsaku Hirai, Geriatrics Research Institute and Hospital, Gunma; Masanori Hirano, Tokyo Metropolitan Police Hospital, Tokyo; Yasuo Ikeda, Keio University, Tokyo; Masayasu Matsumoto, Hiroshima University, Hiroshima; Yoshitaka Miyanaga, Tokyo Women’s Medical University, Tokyo; Mitsuyoshi Nakashima, Aichi Medical University, Aichi; Toshio Okudera, Shinfunagoya Hospital, Fukuoka; Hideki Origasa, University of Toyama Graduate School, Toyama; Yukito Shinohara, Federation of National Public Service Personnel Mutual Aid Associations, Tachikawa Hospital, Tokyo; Makoto Takagi, Saiseikai Central Hospital, Tokyo; Akira Takahashi, Tokai Central Hospital, Gifu; Kunio Tashiro, Health Sciences University of Hokkaido, Hokkaido; Hideo Tohgi, Sobu Hospital, Tokyo.
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Uchiyama, S., Fukuuchi, Y. & Yamaguchi, T. The safety and efficacy of clopidogrel versus ticlopidine in Japanese stroke patients: combined results of two Phase III, multicenter, randomized clinical trials. J Neurol 256, 888–897 (2009). https://doi.org/10.1007/s00415-009-5035-4
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DOI: https://doi.org/10.1007/s00415-009-5035-4