Impact of chronic kidney disease on platelet function profiles in diabetes mellitus patients with coronary artery disease taking dual antiplatelet therapy.
OBJECTIVE
We sought to assess the impact of renal function on platelet reactivity in patients with diabetes mellitus (DM) and coronary artery disease on aspirin and clopidogrel therapy.


BACKGROUND
Diabetes mellitus is a key risk factor for chronic kidney disease (CKD). In aspirin-treated DM patients the presence of moderate/severe CKD is associated with reduced clinical efficacy of adjunctive clopidogrel therapy. Whether these findings may be attributed to differences in clopidogrel-induced effects is unknown.


METHODS
This was a cross-sectional observational study in which DM patients taking maintenance aspirin and clopidogrel therapy were studied. Patients were categorized into 2 groups according to the presence or absence of moderate/severe CKD. Platelet aggregation after adenosine diphosphate (ADP) and collagen stimuli were assessed with light transmittance aggregometry and defined patients with high post-treatment platelet reactivity (HPPR). Markers of platelet activation, including glycoprotein IIb/IIIa activation and P-selectin expression, were also determined using flow cytometry.


RESULTS
A total of 306 DM patients were analyzed. Patients with moderate/severe CKD (n = 84) had significantly higher ADP-induced (60 +/- 13% vs. 52 +/- 15%, p = 0.001) and collagen-induced (49 +/- 20% vs. 41 +/- 20%, p = 0.004) platelet aggregation compared with those without (n = 222). After adjustment for potential confounders, patients with moderate/severe CKD were more likely to have HPPR after ADP (adjusted odds ratio: 3.8, 95% confidence interval: 1.7 to 8.5, p = 0.001) and collagen (adjusted odds ratio: 2.4; 95% confidence interval: 1.1 to 5.4; p = 0.029) stimuli. Markers of platelet activation were significantly increased in patients with HPPR.


CONCLUSIONS
In DM patients with coronary artery disease taking maintenance aspirin and clopidogrel therapy, impaired renal function is associated with reduced clopidogrel-induced antiplatelet effects and a greater prevalence of HPPR.
Angiolillo
Dominick J
DJ
University of Florida College of Medicine-Jacksonville, Jacksonville, Florida 32209, USA. dominick.angiolillo@jax.ufl.edu
Bernardo
Esther
E
Capodanno
Davide
D
Vivas
David
D
Sabaté
Manel
M
Ferreiro
José Luis
JL
Ueno
Masafumi
M
Jimenez-Quevedo
Pilar
P
Alfonso
Fernando
F
Bass
Theodore A
TA
Macaya
Carlos
C
Fernandez-Ortiz
Antonio
A
D000368:Aged; D001241:Aspirin / Q000008:administration & dosage; D001792:Blood Platelets / Q000187:drug effects* / Q000502:physiology; D000077144:Clopidogrel; D003324:Coronary Artery Disease / Q000188:drug therapy*; D003430:Cross-Sectional Studies; D003920:Diabetes Mellitus; D003925:Diabetic Angiopathies / Q000188:drug therapy*; D003928:Diabetic Nephropathies / Q000188:drug therapy*; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage*; D012307:Risk Factors; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D016896:Treatment Outcome
D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin