Differences in Whole Blood Platelet Aggregation at Baseline and in Response to Aspirin and Aspirin Plus Clopidogrel in Patients with vs. without Chronic Kidney Disease

摘要

Thrombotic events while receiving anti-platelet agents (APA) are more common in individuals with vs. without chronic kidney disease (CKD). Data on anti-platelet effects of APA in CKD are scarce and limited by lack of baseline platelet function before APA treatment. We hypothesized individuals with stages 4–5 CKD vs. no CKD have higher baseline platelet aggregability and respond poorly to aspirin and clopidogrel. In a prospective controlled study, we measured whole blood platelet aggregation (WBPA) in 28 CKD and 16 non-CKD asymptomatic stable outpatients not on dual APA, frequency-matched for age, gender, obesity and diabetes mellitus. WBPA was re-measured after 2 weeks of each aspirin and aspirin plus clopidogrel. The primary outcome was percent inhibition of platelet aggregation (IPA) from baseline. The secondary outcome was residual platelet aggregability (RPA) (proportion with <50% IPA). Baseline platelet aggregability was similar between groups except adenosine diphosphate (ADP)-induced WBPA, which was higher in CKD vs. non-CKD; median (IQR) =13.5 (9.5, 16.0) vs. 9.0 (6.0, 12.0) Ω, p=0.007. CKD vs. non-CKD participants had lower clopidogrel-induced IPA, 38% vs. 72%, p=0.04. A higher proportion of CKD vs. non-CKD participants had RPA after clopidogrel treatment (56% vs. 8.3%, p=0.01). There were no significant interactions between CKD and presence of CYP2C19 polymorphisms for platelet aggregability in clopidogrel-treated participants. In conclusion, CKD vs. non-CKD individuals exhibited similar platelet aggregation at baseline, similar aspirin effects and higher residual platelet aggregability on clopidogrel, which was independent of CYP2C19 polymorphisms.