Abstract 1429: Concomitant Use of Sulfonylurea Antidiabetics Attenuates On-Clopidogrel Platelet Reactivity
Introduction The capacity of clopidogrel to inhibit platelet aggregation shows wide interindividual variability. Clopidogrel is a prodrug that needs to be converted in vivo by the cytochrome (CYP) P450 iso-enzymes CYP2C9, CYP2C19, CYP3A, CYP1A2 and CYP2B6 to become active. Concomitant use of drugs that are inhibitors and/or substrates of CYP3A (e.g. calcium channel blockers) and CYP2C19 (e.g. omeprazole) has shown to decrease the platelet inhibitory effect of clopidogrel. Aim The aim of this study was to evaluate the effect of co-administration of sulfonylurea antidiabetics, which are metabolized by CYP2C9, on clopidogrel response in type 2 diabetes mellitus (T2 DM) patients undergoing elective percutaneous coronary intervention (PCI) on dual antiplatelet therapy.
Methods In a total of 158 T2 DM patients undergoing elective PCI treated with clopidogrel and aspirin, on-clopidogrel platelet aggregation to 5, 10 and 20 μM adenosine diphospate (ADP) and high on-clopidogrel platelet reactivity (defined as > 70% platelet aggregation to 20 μM ADP) was evaluated by light transmittance aggregometry.
Results A total of 53 patients (33.5%) were on sulfonylurea antidiabetics, six of these patients also received insulin. The remaining 105 patients were on (combinations of) other oral hypoglycemic drugs and insulin. Mean ADP-induced on-clopidogrel platelet aggregation was significantly higher in sulfonylurea antidiabetics users as compared to non-users (all p<0.05). Mean differences remained significant after adjusting for the confounding factors sex, age, BMI and use of insulin (adjusted mean differences: 6.2% 95% CI, 0.9 –11.5 for 5 μM, p=0.023; 7.1% 95% CI, 1.7–12.5, for 10 μM ADP, p=0.010; and 6.5% 95% CI, 1.4 –11.5, for 20 μM, p=0.013). After covariate adjustment the use of sulfonylurea antidiabetics was also associated with high on-clopidogrel platelet reactivity: ORadj: 2.3 95% CI 1.0 –5.3; p=0.043.
Conclusions This study demonstrates that concomitant use of sulfonylurea antidiabetics is associated with a blunted response to clopidogrel in T2 DM patients undergoing elective PCI on dual antiplatelet therapy.