Clopidogrel preventive effect based on cytochrome P450 2C19 genotype in ischaemic stroke: protocol for multicentre observational study

• Published in: BMJ open Vol. 10; no. 8; p. e038031
• Main Authors: Song, Tae-Jin, Kim, Jinkwon, Han, Sang Won, Kim, Young Dae, Lee, Jong Yun, Ahn, Seong Hwan, Lee, Hye Sun, Jung, Yo Han, Lee, Kyung-Yul
• Format: Journal Article
• Language: English
• Published: England British Medical Journal Publishing Group 05.08.2020; BMJ Publishing Group LTD; BMJ Publishing Group
• Series: Protocol
• Subjects: Aspirin; Blood platelets; Brain Ischemia - drug therapy; Brain Ischemia - genetics; Brain Ischemia - prevention & control; Cardiovascular disease; Clopidogrel - therapeutic use; Coronary vessels; Cytochrome; Cytochrome P-450 CYP2C19 - genetics; Disease prevention; Genotype; Genotype & phenotype; Heart attacks; Humans; Hypotheses; Informed consent; Ischemic Stroke; Metabolism; Metabolites; Multicenter Studies as Topic; neurogenetics; Neurology; Observational studies; Observational Studies as Topic; Patients; Platelet Aggregation Inhibitors - therapeutic use; Prospective Studies; Stroke; Stroke - genetics; Stroke - prevention & control; Ticlopidine - therapeutic use; Treatment Outcome; stroke; neurology; neurogenetics
• ISSN: 2044-6055; 2044-6055
• DOI: 10.1136/bmjopen-2020-038031

IntroductionClopidogrel is an antiplatelet agent that is widely used for the secondary prevention of cardiovascular and cerebrovascular events. The genotype of cytochrome P450 2C19 (CYP2C19) differentially affects the liver’s metabolism of clopidogrel, which may influence the drug’s response and efficacy for cardiovascular event prevention. In contrast to prior studies of patients with coronary artery diseases, little is known about whether the CYP2C19 genotype influences the preventive efficacy of clopidogrel in patients who had a stroke. We hypothesise that, among patients who had an acute ischaemic stroke who are prescribed clopidogrel, the patients with a loss-of-function CYP2C19 genotype (poor and intermediate metabolisers) may be at a higher risk of composite cardiovascular events than those who are non-carriers (extensive metabolisers).Methods and analysisThis prospective observational multicentre study was designed to determine whether composite cardiovascular events would differ among patients who had an ischaemic stroke prescribed clopidogrel according to CYP2C19 genotype (poor or intermediate vs extensive metabolisers). Inclusion criteria were patients who had an acute ischaemic stroke who underwent CYP2C19 genotype evaluation and received clopidogrel within 72 hours of stroke onset. The primary outcome is composite cardiovascular events (stroke, myocardial infarction, or cardiovascular death) within 6 months after acute ischaemic stroke between patients categorised as poor or intermediate metabolisers and those categorised as extensive metabolisers according to their CYP2C19 genotype.Ethics and disseminationThe Institutional Review Board of Severance Hospital, Yonsei University College of Medicine approved this study (3-2019-0195). We received study approval from the institutional review board of each participating hospital. We plan to disseminate our findings at relevant conferences and meetings and through peer-reviewed journals.Trial registration numberNCT04072705.