Amlodipine, clopidogrel and CYP3A5 genetic variability: effects on platelet reactivity and clinical outcomes after percutaneous coronary intervention
Park KW et al. – Treatment with amlodipine is associated with increased clopidogrel on–treatment platelet reactivity (OPR) and increased risk of thrombotic events after percutaneous coronary intervention (PCI), which is dependent on the CYP3A5 genetic status.Methods
- Post hoc analysis of a prospectively enrolled cohort.
- Patients enrolled in the CROSS–VERIFY cohort from June 2006 to June 2010, with successful genotyping of CYP3A5.
- The pharmacodynamic analysis end point was clopidogrel on–treatment platelet reactivity (OPR) and the clinical analysis end point was the composite of cardiac death, non–fatal myocardial infarction, ischaemic stroke and stent thrombosis at 12 months post–PCI.
- 1258 patients had successful genotyping and were categorised as CYP3A5 non–expressers (749 patients) and expressers (509 patients) according to the CYP3A5 genotype.
- Amlodipine users showed higher OPR versus non–users only in CYP3A5 non–expressers (249±83 vs 228±84 P2Y12 reaction units, p=0.013).
- These findings was corroborated by clinical outcomes, in which amlodipine users had a higher incidence of events compared with non–users only in CYP3A5 non–expressers (4.6% vs 0.6%, HR 7.731, CI 2.042 to 29.264, p=0.004).