The potential interaction of statins and clopidogrel in patients undergoing percutaneous coronary intervention

Abstract

Clopidogrel is widely used for patients with acute coronary syndrome. It is a pro-drug that requires bioactivation by several cytochrome P450 (CYP) enzymes, mainly CYP3A4, CYP2C9, and CYP2C19 enzymes. Lipophilic statins such as atorvastatin are used concomitantly with clopidogrel due to their beneficial effects on morbidity and mortality in the arena of cardiovascular diseases. However, lipophilic statins are eliminated by CYP3A4 and undergo the same metabolic pathway of clopidogrel. Hence, statins may compete with clopidogrel for CYP3A4 enzyme resulting in diminishing the anti-platelet effect of clopidogrel. We aimed to study the impact of concomitant statin therapy on clopidogrel efficacy in patients undergoing percutaneous coronary intervention (PCI) evaluate the clinical relevance of potential clopidogrel and statins interaction and association between use of statins and risk of future adverse cardiac events. A cross-sectional retrospective cohort study was conducted on 50 patients attending Prince Sultan Cardiac Center for follow-up after PCI. All patients discharged on clopidogrel, aspirin, and atorvastatin were later divided into two groups according to the occurrence of MACEs. Statistical analysis was performed by Statistical Package for the Social Science (SPSS; V. 21.0). This study was on adult and geriatric males (72%)and female (28%). More than half of them exhibited major adverse cardiac events (MACEs), of which 48% exhibited it after 4 to 6 months from PCI indexing followed by 1 to 3 months (34%), and the least after 7 to 9 months. A significant association arises between gender and MACEs (P=0.042). Moreover, the average age was significantly higher in patients who experience MACEs compared to others (62.7 vs. 55.4, P=0.037). Regarding comorbidities, hypertension increased in patients with MACEs (73.1%) compared to those without MACEs (45.8%). The average duration of taking clopidogrel was significantly shorter in patients with MACEs compared to those who did not (3.42 vs. 5.54 months, P<0.001). According to the findings of this study, atorvastatin affects clopidogrel efficacy in patients undergoing PCI.