Impact of Chronic Kidney Disease on Platelet Function Profiles in Diabetes Mellitus Patients With Coronary Artery Disease Taking Dual Antiplatelet Therapy
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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.
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Aspirin and clopidogrel-based dual antiplatelet responsiveness can be reduced in type 2 diabetes, and chronic kidney disease worsens this.
“responsiveness to aspirin40 and clopidogrel-based dual antiplatelet therapy41 may be impaired in the setting of T2DM,41,42 which is further exacerbated in patients with concomitant chronic kidney disease.43”
From Clinical management of stable coronary artery disease in patients with type 2 diabetes mellitus: a scientific statement from the American Heart Association (2020) · cites this paper as [43]
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Research works printed but not linked: 2
- Angiolillo DJ, Bernardo E, Sabaté M, et al. Impact of platelet reactivity on cardiovascular outcomes in patients with type 2 diabetes 1145 JACC Vol. 55, No. 11, 2010
- Angiolillo et al. March 16, 2010:1139-46 Clopidogrel Effects and Renal Function in Diabetes mellitus and coronary artery disease. J Am Coll Cardiol 2007;50: 1541-7.
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Self-citation
- Authors
- Angiolillo, D. J., Bernardo, E., Capodanno, D., Vivas, D., Sabaté, M., Ferreiro, J. L., Ueno, M., Jimenez-Quevedo, P., Alfonso, F., Bass, T. A., Macaya, C., & Fernandez-Ortiz, A.
- Affiliations
- University of Florida (US)
- Hospital Clínico San Carlos (ES)
- Corresponding author
- Angiolillo, Dominick J.
- ORCID
- Venue
- Journal of the American College of Cardiology
- Publisher
- Elsevier BV
- Published
- 2010-03
- Volume
- 55
- Issue
- 11
- Pages
- 1139-1146
- ISSN
- 0735-1097 (ISSN-L)
- OpenAlex
- W2162756930
- Cited by
- 220
- References
- 50
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 3 · 2023: 9 · 2022: 14 · 2021: 12 · 2020: 9 · 2019: 12 · 2018: 11 · 2017: 12 · 2016: 15 · 2015: 20 · 2014: 19 · 2013: 19 · 2012: 31
- FWCI
- 17.34
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Journal of the American College of Cardiology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- GlaxoSmithKline
- Otsuka
- Eli Lilly
- Daiichi Sankyo
- The Medicines Company
- Portola
- Accumetrics
- Schering-Plough
- Astra-Zeneca
- Eisai
- Baxter
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Antiplatelet Therapy and Cardiovascular Diseases
- Health Sciences › Medicine › Hematology › Platelet Disorders and Treatments
- Health Sciences › Medicine › Hematology › Blood Coagulation and Thrombosis Mechanisms
- Keywords
- chronic kidney disease, platelet function, diabetes mellitus, coronary artery disease, dual antiplatelet therapy, clopidogrel, aspirin, platelet aggregation, P-selectin, renal function
- MeSH terms
- Clopidogrel, Aged, Aspirin, Blood Platelets, Coronary Artery Disease, Cross-Sectional Studies, Diabetes Mellitus, Diabetic Angiopathies, Diabetic Nephropathies, Drug Therapy, Combination, Female, Humans, Male, Middle Aged, Platelet Aggregation Inhibitors, Risk Factors, Ticlopidine, Treatment Outcome
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