Sarah Jafrin1, Nura Ershad Naznin1, Md Sharif Reza1, Md Abdul Aziz1, Mohammad Safiqul Islam2. 1. Department of Pharmacy, Faculty of Science, Noakhali Science and Technology University, Sonapur 3814, Noakhali, Bangladesh. 2. Department of Pharmacy, Faculty of Science, Noakhali Science and Technology University, Sonapur 3814, Noakhali, Bangladesh. Electronic address: research_safiq@nstu.edu.bd.
Abstract
BACKGROUND: Antiplatelet agent clopidogrel has been widely used for stroke management for many years, although resistance to clopidogrel may increase the chance of stroke recurrence. CYP2C19 loss-of-function (LoF) polymorphism is assumed to be responsible for the poor metabolism of clopidogrel that ultimately turns to resistance. Previous publications could not provide firm evidence due to highly conflicting and heterogeneous outcomes. AIM: To get clear evidence from an updated meta-analysis on CYP2C19 LoF polymorphism association with stroke risk in clopidogrel treated patients, this study has been performed. METHODS: We conducted a meta-analysis with 72 selected studies from authentic databases, including 40,035 coronary artery disease patients treated with clopidogrel. RESULTS: This analysis showed that the worldwide carrier of one or more CYP2C19 LoF alleles had a significantly higher risk of stroke and composite events than the non-LoF carriers (RR=1.78, 95% CI=1.52-2.07, p<0.00001 and RR=1.39, 95% CI=1.26-1.54, p<0.00001, respectively). Besides, subgroup analysis showed that Asian CYP2C19 LoF carriers had a significantly increased risk of stroke (RR=1.91, 95% CI=1.60-2.28, p<0.00001) while the risk of composite events was significantly higher in all ethnic populations (Asian: RR=1.58, 95% CI=1.32-1.89, p<0.00001; Caucasian: RR=1.27, 95% CI=1.08-1.50, p=0.003; Hispanic and others: RR=1.21, 95% CI=1.09-1.34, p=0.0003). CONCLUSION: Our meta-analysis confirmed that the presence of CYP2C19 LoF alleles increases the risk of stroke and composite events recurrence in the worldwide population, especially in Asians undergoing clopidogrel treatment. Alternative antiplatelet therapy should be investigated thoroughly for the intermediate and poor metabolizers.
BACKGROUND: Antiplatelet agent clopidogrel has been widely used for stroke management for many years, although resistance to clopidogrel may increase the chance of stroke recurrence. CYP2C19 loss-of-function (LoF) polymorphism is assumed to be responsible for the poor metabolism of clopidogrel that ultimately turns to resistance. Previous publications could not provide firm evidence due to highly conflicting and heterogeneous outcomes. AIM: To get clear evidence from an updated meta-analysis on CYP2C19 LoF polymorphism association with stroke risk in clopidogrel treated patients, this study has been performed. METHODS: We conducted a meta-analysis with 72 selected studies from authentic databases, including 40,035 coronary artery diseasepatients treated with clopidogrel. RESULTS: This analysis showed that the worldwide carrier of one or more CYP2C19 LoF alleles had a significantly higher risk of stroke and composite events than the non-LoF carriers (RR=1.78, 95% CI=1.52-2.07, p<0.00001 and RR=1.39, 95% CI=1.26-1.54, p<0.00001, respectively). Besides, subgroup analysis showed that Asian CYP2C19 LoF carriers had a significantly increased risk of stroke (RR=1.91, 95% CI=1.60-2.28, p<0.00001) while the risk of composite events was significantly higher in all ethnic populations (Asian: RR=1.58, 95% CI=1.32-1.89, p<0.00001; Caucasian: RR=1.27, 95% CI=1.08-1.50, p=0.003; Hispanic and others: RR=1.21, 95% CI=1.09-1.34, p=0.0003). CONCLUSION: Our meta-analysis confirmed that the presence of CYP2C19 LoF alleles increases the risk of stroke and composite events recurrence in the worldwide population, especially in Asians undergoing clopidogrel treatment. Alternative antiplatelet therapy should be investigated thoroughly for the intermediate and poor metabolizers.
Authors: Juan Tamargo; Juan Carlos Kaski; Takeshi Kimura; Jack Charles Barton; Ko Yamamoto; Maki Komiyama; Heinz Drexel; Basil S Lewis; Stefan Agewall; Koji Hasegawa Journal: Eur Heart J Cardiovasc Pharmacother Date: 2022-09-29