CLINICAL RESEARCH: PLATELETS AND THROMBOSIS
Impact of Chronic Kidney Disease on Platelet Function Profiles in Diabetes Mellitus Patients With Coronary Artery Disease Taking Dual Antiplatelet Therapy
Dominick J. Angiolillo, MD, PhD*,*,
Esther Bernardo, BSc ,
Davide Capodanno, MD*,
David Vivas, MD,
Manel Sabaté, MD, PhD,
José Luis Ferreiro, MD*,
Masafumi Ueno, MD*,
Pilar Jimenez-Quevedo, MD, PhD,
Fernando Alfonso, MD, PhD,
Theodore A. Bass, MD*,
Carlos Macaya, MD, PhD and
Antonio Fernandez-Ortiz, MD, PhD
* University of Florida College of Medicine-Jacksonville, Jacksonville, Florida
Cardiovascular Institute–San Carlos University Hospital, Madrid, Spain
Manuscript received July 3, 2009;
revised manuscript received September 18, 2009,
accepted October 6, 2009.
* Reprint requests and correspondence: Dr. Dominick J. Angiolillo, University of Florida College of Medicine-Jacksonville, 655 West 8th Street, Jacksonville, Florida 32209 (Email: dominick.angiolillo{at}jax.ufl.edu).
Objectives: 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.
Key Words: clopidogrel • chronic kidney disease • diabetes mellitus • platelets
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Abbreviations and Acronyms
| | ADP = adenosine diphosphate | | CAD = coronary artery disease | | CI = confidence interval | | CKD = chronic kidney disease | | DM = diabetes mellitus | | HPPR = high post-treatment platelet reactivity | | MI = myocardial infarction | | OR = odds ratio | | PCI = percutaneous coronary intervention |
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