Revaluation of clopidogrel: let the data speak for themselves.
Clopidogrel was believed to be superior to aspirin by the well-known CAPRIE trial. However, no other large clinical trials demonstrated the same results, but all focused on the combination use of clopidogrel with aspirin, and combination therapy in CREDO was called the "Emperor's New Clothes". However, no one overturned the results of these clinical trials by quantitatively analyzing them. We reviewed ten large-scale clinical trials about clopidogrel. On the basis of results of CAPRIE, CREDO and CHARISMA trials, we re-estimated their minimal sample sizes and their powers by three well-established statistical methodologies. From the results of CAPRIE, we inferred that the minimal sample size should be 85 086 or 84 968 but its power was only 30.70%. A huge gap existed. The same was also true of CREDO and CHARISMA trials. Moreover, in CAPRIE trial, 0 was included in the 95% confidence interval and 1 was included in the 95% confidence interval for the relative risk. There were some paradoxical data in CAPRIE trial. We are led to conclude that the results in CAPRIE, CREDO, and from the subgroup analysis in CHARISMA trials were questionable. These results failed to demonstrate that clopidogrel was superior to aspirin or that clopidogrel used in combination with aspirin was better than aspirin alone. The cost-effectiveness analyses by some previous studies were not reliable.
Liu
Li
L
Institute of Clinical Pharmacology, Department of Pharmacology, Tongji Medical College, Huazhong University of Science and Technology, and Department of Radiology, Renmin Hospital, Wuhan, 430030, China. LLsunrising@126.com
Zeng
Fandian
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Zeng
Xiaohua
X
Xue
Qingmei
Q
Nie
Shaoping
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Kang
Cailian
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Wu
Jianhong
J
Kang
Qingyun
Q
Wang
Xingao
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Liu
Xiaoqing
X
Li
Tao
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Chen
Jun
J
Li
Qing
Q
Xu
Rong
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Yang
Xiaoyan
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Kang
Hui
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Jiang
Fagang
F
Li
Zongtao
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Wang
Xuwu
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Zhang
Li
L
Long
Yu
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D001157:Arterial Occlusive Diseases / Q000188:drug therapy* / Q000517:prevention & control; D001241:Aspirin / Q000627:therapeutic use; D000077144:Clopidogrel; D003362:Cost-Benefit Analysis; D004359:Drug Therapy, Combination; D006801:Humans; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000627:therapeutic use
D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin