title: Differences in Whole Blood Platelet Aggregation at Baseline and in Response to Aspirin and Aspirin Plus Clopidogrel in Patients With Versus Without Chronic Kidney Disease.
abstract: Thrombotic events while receiving antiplatelet agents (APAs) are more common in subjects with versus without chronic kidney disease (CKD). Data on antiplatelet effects of APA in CKD are scarce and limited by lack of baseline platelet function before APA treatment. We hypothesized subjects with stages 4 to 5 CKD versus no CKD have greater 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 APA, frequency-matched for age, gender, obesity, and diabetes mellitus. WBPA was remeasured 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-induced WBPA, which was higher in CKD versus non-CKD; median (interquartile range) = 13.5 (9.5 to 16.0) versus 9.0 (6.0 to 12.0) Ω, p = 0.007. CKD versus non-CKD participants had lower clopidogrel-induced IPA, 38% versus 72%, p = 0.04. A greater proportion of CKD versus non-CKD participants had RPA after clopidogrel treatment (56% vs 8.3%, p = 0.01). There were no significant interactions between CKD and the presence of cytochrome P450 2C19 polymorphisms for platelet aggregability in clopidogrel-treated participants. In conclusion, CKD versus non-CKD subjects exhibited similar platelet aggregation at baseline, similar aspirin effects and greater RPA on clopidogrel, which was independent of cytochrome P450 2C19 polymorphisms.
authors.affiliation: Department of Internal Medicine, Kidney Institute, University of Kansas Medical Center, Kansas City, Kansas.
authors.forename: Nishank
authors.initials: N
authors.lastname: Jain
authors.affiliation: Division of Biostatistics, Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, Texas.
authors.forename: Xilong
authors.initials: X
authors.lastname: Li
authors.affiliation: Division of Biostatistics, Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, Texas.
authors.forename: Beverley
authors.initials: B
authors.lastname: Adams-Huet
authors.affiliation: Department of Pathology, University of Texas Southwestern Medical Center, Dallas, Texas.
authors.forename: Ravi
authors.initials: R
authors.lastname: Sarode
authors.affiliation: Division of Nephrology, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas.
authors.forename: Robert D
authors.initials: RD
authors.lastname: Toto
authors.affiliation: Division of Cardiology, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas; Division of Cardiology, Department of Internal Medicine, Veterans Affairs North Texas Health Care System, Dallas, Texas.
authors.forename: Subhash
authors.initials: S
authors.lastname: Banerjee
authors.affiliation: Division of Nephrology, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas; Division of Nephrology, Department of Internal Medicine, Veterans Affairs North Texas Health Care System, Dallas, Texas. Electronic address: susan.hedayati@utsouthwestern.edu.
authors.forename: S Susan
authors.initials: SS
authors.lastname: Hedayati
mesh_terms: D001241:Aspirin / Q000008:administration & dosage*; D000077144:Clopidogrel; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage; D010979:Platelet Function Tests; D011446:Prospective Studies; D051436:Renal Insufficiency, Chronic / Q000097:blood* / Q000150:complications; D013927:Thrombosis / Q000097:blood / Q000150:complications / Q000517:prevention & control*; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D016896:Treatment Outcome
chemical_list: D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin