Key result
Mild acute ischemic stroke linked to lower clopidogrel active metabolite Cmax versus healthy controls.
Why the study?
Inflammatory states like acute ischaemic stroke may cause CYP2C19 phenoconversion, temporarily reducing enzyme activity and impairing clopidogrel activation.
Does mild acute ischaemic stroke reduce CYP2C19 activity and clopidogrel activation compared to healthy controls?
Observational (n=33)
Does mild acute ischaemic stroke reduce CYP2C19 activity and clopidogrel activation compared to healthy controls?
Acute ischaemic stroke induces CYP2C19 phenoconversion, reducing clopidogrel activation regardless of genotype, suggesting genotyping alone may be insufficient to identify poor metabolizers.
Answers are grounded in this paper and cite their sources.
May reduce clopidogrel activation in mild stroke regardless of genotype; leaves open whether phenoconversion warrants adjusted monitoring or dosing.
Aim Ischaemic stroke is a global health issue, and clopidogrel is widely used for secondary prevention and undergoes hepatic activation by cytochrome 2C19 ( CYP2C19 ) into its active thiol metabolite (H4‐clopi). Although genetic polymorphisms are key determinants of this process, inflammatory states, such as acute ischaemic stroke, may cause phenotype–genotype mismatch (phenoconversion) and temporarily reduce CYP2C19 enzyme activity. Method This pharmacokinetic study was performed in Iranian patients with mild acute ischaemic stroke (NIHSS ≤ 5) who were prescribed clopidogrel for 21 days. Genotyping was conducted by real‐time PCR. CYP2C19 activity and Clopidogrel metabolism were assessed in both the acute and post‐acute phase (21 days after acute ischaemic stroke) by using the omeprazole metabolic ratio (MR) and the maximum plasma concentration (Cmax) of H4‐clopi, respectively. Laboratory parameters and demographic characteristics were also recorded. Results Thirty‐three patients were enrolled (mean age 63 ± 10.5 years; 66% male). Genotype results were consistent with previous reports in ethnically matched healthy populations. CYP2C19 activity was significantly reduced in the acute phase and recovered only partially in the post‐acute phase. Regardless of genotype, H4‐clopi Cmax was significantly lower in ischaemic stroke patients than in healthy controls in both phases, with no significant interphase improvement ( p < 0.05). Inflammatory markers and NIHSS scores significantly decreased in the post‐acute phase ( p < 0.05). Conclusion These findings demonstrate that genotyping alone may be insufficient to identify poor metabolizers, highlighting the importance of direct measurement of CYP2C19 activity and consideration of alternative antiplatelet approaches.
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Alaei et al. (2026) conducted an observational in Mild acute ischaemic stroke (n=33). Mild acute ischaemic stroke vs. Healthy controls was evaluated on H4-clopi maximum plasma concentration (Cmax) (p=<0.05). Mild acute ischaemic stroke was associated with lower clopidogrel active metabolite Cmax compared to healthy controls in both acute and post-acute phases.
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