Related Experiment Video

Updated: Oct 3, 2025

A Method to Study the C924T Polymorphism of the Thromboxane A2 Receptor Gene
07:00

A Method to Study the C924T Polymorphism of the Thromboxane A2 Receptor Gene

Published on: April 1, 2019

10.1K

Increased frequency of CYP2C19 loss-of-function alleles in clopidogrel-treated patients with recurrent cerebral

Crista Minderhoud1,2, Leila S Otten2,3, Pieter H E Hilkens2

  • 1University Medical Center Utrecht, Utrecht, Netherlands.

British Journal of Clinical Pharmacology
|February 17, 2022
PubMed

Insights

Genetic variations in CYP2C19 increase stroke risk in clopidogrel-treated patients. Higher CYP2C19 loss-of-function allele frequency was observed in European patients with recurrent cerebral ischaemia, suggesting genotype-guided therapy benefits.

Area of Science:

  • Pharmacogenomics
  • Neurology
  • Cardiology

Background:

  • Clopidogrel is a key antiplatelet medication for secondary stroke prevention.
  • Genetic variations in CYP2C19 influence clopidogrel efficacy.
  • Previous studies on CYP2C19 and stroke risk were mainly from Asian populations.

Purpose of the Study:

  • To investigate the prevalence of CYP2C19 loss-of-function (LoF) alleles in European patients experiencing recurrent cerebral ischaemia.
  • To compare these allele frequencies with regional reference groups.

Main Methods:

  • CYP2C19 genotyping (*2 and *3 alleles) was conducted on clopidogrel-treated patients with recurrent ischaemic stroke or transient ischaemic attack (TIA).
  • Genotype distributions were compared against two control groups: cardiology patients undergoing coronary stent implantation and healthy Dutch volunteers.

Main Results:

  • 43.6% of patients with recurrent cerebral ischaemia carried at least one CYP2C19 LoF allele, significantly higher than in cardiology (27.6%) and healthy (24.7%) groups (P < .001).
  • Patients experiencing early recurrent events (within 90 days) showed an even higher prevalence of LoF alleles (55.3%, P < .0001).

Conclusions:

  • The frequency of CYP2C19 LoF alleles is significantly elevated in European patients with recurrent cerebral ischaemia treated with clopidogrel.
  • These findings underscore the importance of genotype-guided antiplatelet therapy to potentially improve outcomes in this patient population.
Abstract

Keywords:
CYP2C19cerebral ischaemiaclopidogrelgenetic variantssecondary preventionstroketransient ischaemic attack

More Related Videos

Microfluidics in Assessing Platelet Function06:47

Microfluidics in Assessing Platelet Function

Published on: November 8, 2024

1.1K
Point of Care Transcranial Color-Coded Duplex Ultrasound of the Middle Cerebral Artery04:01

Point of Care Transcranial Color-Coded Duplex Ultrasound of the Middle Cerebral Artery

Published on: August 9, 2024

1.0K

Related Concept Videos

Antiplatelet Drugs: Prostaglandin Synthesis, P2Y12 and Glycoprotein IIb/IIIa Inhibitors01:20

Antiplatelet Drugs: Prostaglandin Synthesis, P2Y12 and Glycoprotein IIb/IIIa Inhibitors

Antiplatelet drugs emerge as frontline defenders against the insidious threat of thromboembolic diseases, where abnormal clots obstruct vital blood vessels. These drugs stand as bulwarks, inhibiting platelet aggregation and clot formation, thereby mitigating the risk of life-threatening conditions like myocardial infarction, coronary artery disease, and thrombotic strokes.
Prostaglandin synthesis inhibitors, exemplified by the widely known aspirin, wield their power by irreversibly acetylating...
682
Nonlinear Pharmacokinetics: Dependence of Elimination Half-Life and Dose Clearance01:23

Nonlinear Pharmacokinetics: Dependence of Elimination Half-Life and Dose Clearance

The elimination half-life and drug clearance of drugs following nonlinear kinetics can vary with dosage. The Michaelis-Menten parameters and drug concentration influence these factors. As the dose increases, the elimination half-life tends to lengthen, resulting in a reduction in clearance and a disproportionately larger area under the curve. The total clearance can be derived from the Michaelis-Menten equation for drugs following a one-compartment model.
A study on guinea pigs examined the...
332
Factors Influencing Drug Absorption: Disease States and Pharmacology01:25

Factors Influencing Drug Absorption: Disease States and Pharmacology

Multiple disease states can significantly influence the oral drug absorption process by affecting blood flow and the functionality of the gastrointestinal (GI) system. Various GI diseases, including conditions that alter GI motility, such as diarrhea, decreased acid secretions (achlorhydria), and infections, have been associated with reduced drug absorption.
Substances such as alcohol and specific drugs, including antineoplastics, can also negatively impact drug absorption. For instance,...
906
Chronopharmacokinetics: Circadian Rhythms and Influence on Drug Response01:15

Chronopharmacokinetics: Circadian Rhythms and Influence on Drug Response

Circadian rhythms are cyclic changes that are crucial in plasma drug concentrations. Various standard circadian parameters, including core body temperature, heart rate, and other cardiovascular factors, directly impact disease states and the therapeutic response to drug therapy.
The time of drug administration is an important factor to consider, as it can influence the toxic dose of a drug. For example, a study conducted by Prins et al. in 1997 examined the effects of the timing of...
148
Desensitization and Tachyphylaxis01:20

Desensitization and Tachyphylaxis

Tachyphylaxis is described as a rapid decrease in response to a drug after repeated or continuous administration of the same drug dose. It is a phenomenon where the body becomes less responsive to a particular substance or intervention over time, requiring higher doses or stronger interventions to achieve the same effect. It results from adaptive changes in the body's receptors, signaling pathways, or physiological processes that occur in response to prolonged exposure to a stimulus.
2.4K
Factors Affecting Drug Response: Overview01:21

Factors Affecting Drug Response: Overview

When it comes to infants and young children, they are typically administered smaller doses of medication in comparison to adults. This is primarily because their organ functions still need to fully develop, meaning their bodies are not as efficient at metabolizing or eliminating drugs. Additionally, their blood-brain barrier is more permeable than in adults. As a result, high concentrations of drugs can easily penetrate the central nervous system (CNS), potentially leading to neurological...
2.5K