The influence of CYP2C19 polymorphisms on clinical efficacy of clopidogrel in Sudanese patients undergoing percutaneous coronary intervention

Abstract

Clopidogrel is commonly used anti-platelet drugs in treatment of patients undergoing percutaneous coronary intervention (PCI). It was documented that CYP2C19 loss of function variants may affect clopidogrel efficacy and exposed patients to risk of adverse cardiac events. This study aimed to appraise the link between CYP2C19 polymorphisms and adverse clinical outcomes in Sudanese patients undergoing PCI. This prospective observational cohort study recruited 197 PCI patients from Wad Medani Heart Diseases and Surgery Center from 2017 to 2021. The patients   were distributed into three groups according to their genotype results as follow: Extensive metabolizers (EMs) 136, Intermediate metabolizers (IMs) 56, and Poor metabolizers (PMs) 5. All study cohort received aspirin and clopidogrel. Clinical ends points were evaluated after 12 months from PCI indexing by rechecking patients' records. The metabolizing capacity among the groups did not show significant relations to demographics and clinical characteristics (P>0.05), except that PMs showed a significantly higher mean body weight than IMs (P=0.010). Ischemic heart disease was significantly higher among PMs in comparison to IMs and EMs (60.0% versus 5.5% and 11.0% respectively, P=0.006). Previous angiography was also significantly more common among PMs in comparison to IMs and NMs (60.0% versus 8.9% and 9.6% respectively, P=0.013). The frequency of adverse cardiac events (ACEs) was higher among PMs in comparison to IMs and EMs (40% vs 16.1%, 10.3%), however no significant association found between ACEs and the metabolizer capacity (P=0.078). On the other hand, revascularization was significantly related to the metabolizer capacity, where 40.0% of PMs developed revascularization compared to 7.1% in IMs and 4.4% in EMs (P=0.029). The risk of revascularization was 14.44 (2.019-103.317) in PMs and 1.67 (0.452-6.149) in IMs. In conclusion ACEs was more prevalent among PMs in comparison to IMs and EMs. Moreover, revascularization was significantly higher among PMs in comparison to IMs and EMs.