No rebound effect after a course of clopidogrel in patients with acute TIA or minor stroke

ABSTRACT

Background and Purpose

Previous studies demonstrated that discontinuation of clopidogrel in patients after ACS was associated with a rebound increase in risk of recurrent events. In this study, we aimed to investigate the rebound effect after discontinuation of clopidogrel therapy in patients with TIA or stroke.

Methods

All patients with minor stroke or TIA were recruited from the Clopidogrel in High-Risk Patients With Acute Nondisabling Cerebrovascular Events (CHANCE) trial. Patients were divided into two groups: patients who discontinued clopidogrel and switched to aspirin therapy   (Clopidogrel Discontinuation Group) and patients who continued one mono-antiplatelet therapy (non-Clopidogrel Discontinuation Group) during 90-180  days. The outcomes included risks of recurrent ischemic stroke, recurrent TIA, and composite events during 90-180  days. The prevalence of each outcome was compared between two groups for every 30 days. Further subgroup analysis was conducted in patients with and without CYP2C19 loss-of-function alleles.

Results

Among the 3456 patients included, a total of 10 patients in the Clopidogrel Discontinuation Group and 11 patients in the non-Clopidogrel Discontinuation Group presented ischemic stroke recurrence during the 90–180-day period. The inter-group comparisons were not significant in each 30 days. Similar results were found for recurrent stroke, recurrent TIA, and composite events in these two groups, which were also found in CYP2C19 subgroup analysis.

Conclusions

No rebound increase in the risk of ischemic stroke and composite events was found during the 90 days after discontinuation of clopidogrel therapy in patients with TIA or minor stroke in the CHANCE trial.

Trial Registration

clinicaltrials.gov Identifier: NCT00979589

KEYWORDS:

• Rebound
• clopidogrel
• discontinuation
• minor stroke
• transient ischemic attacks

Acknowledgments

We thank all investigators and participating hospitals of the CHANCE trial.

Contributorship statement

Xinmiao Zhang and Jing Jing analyzed and interpreted the data and drafted the manuscript. Anxin Wang and Yuesong Pan completed the statistical work. Xingquan Zhao, Liping Liu, David Wang, S. Claiborne Johnston, Yilong Wang, Yongjun Wang, and Xia Meng conceived and designed the research.

Data availability statement

The data that support the findings of this study are available from the corresponding author upon reasonable request http://paper.ncrcnd.ttctrc.com/default/project-detail?id=248

Disclosure statement

No potential conflict of interest was reported by the authors.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/01616412.2022.2075660

Additional information

Funding

This study is supported by grants from the Capital’s Funds for Health Improvement and Research (2020-1-2041), Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences (2019-I2M-5-029), National Natural Science Foundation of China (81870905, U20A20358), and National Key R&D Program of China (2018YFC1312903).

Notes on contributors

Xinmiao Zhang

Xinmiao Zhang. She is major in neurology, especially in stroke. She works in the Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China, and China National Clinical Research Center for Neurological Diseases as well.

Jing Jing

Jing Jing. He is major in neurology, especially in stroke. He works in the Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China, and China National Clinical Research Center for Neurological Diseases as well.

Xingquan Zhao

Xingquan Zhao. He is major in neurology, especially in stroke. He works in the Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China, and China National Clinical Research Center for Neurological Diseases as well. He is the chief of our department.

Yuesong Pan. He is major in statistics and works in China National Clinical Research Center for Neurological Diseases.

Yilong Wang. He is major in neurology, especially in stroke. He works in the Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China, and China National Clinical Research Center for Neurological Diseases as well.

Yongjun Wang, MD. He is major in neurology, especially in stroke. He works in the Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China, and China National Clinical Research Center for Neurological Diseases as well. He is the chief of our hospital.

Xia Meng. She is major in neurology, especially in stroke. She works in the Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China, and China National Clinical Research Center for Neurological Diseases as well. She is the chief of the department.

Liping Liu

Liping Liu. She is major in neurology, especially in stroke. She works in the Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China, and China National Clinical Research Center for Neurological Diseases as well.

Anxin Wang

Anxin Wang. He is major in statistics and works in China National Clinical Research Center for Neurological Diseases.

Yuesong Pan

Yuesong Pan. He is major in statistics and works in China National Clinical Research Center for Neurological Diseases.

David Wang

David Wang. He is major in neurology, especially in stroke. He works in the Neurovascular Division, Department of Neurology, Barrow Neurological Institute, St. Joseph’s Hospital and Medical Center.

S. Claiborne Johnston

S. Claiborne Johnston. He is major in neurology, especially in stroke. He works in the Dell Medical School, University of Texas at Austin.

Yilong Wang

Yilong Wang. He is major in neurology, especially in stroke. He works in the Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China, and China National Clinical Research Center for Neurological Diseases as well.

Yongjun Wang

Yongjun Wang, MD. He is major in neurology, especially in stroke. He works in the Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China, and China National Clinical Research Center for Neurological Diseases as well. He is the chief of our hospital.

Xia Meng

Xia Meng. She is major in neurology, especially in stroke. She works in the Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China, and China National Clinical Research Center for Neurological Diseases as well. She is the chief of the department.