title: Antiplatelet effects of aspirin in chronic kidney disease patients.
abstract: ESSENTIALS: Chronic kidney disease (CKD) patients have a high risk of cardiovascular events. A pharmacodynamic evaluation of the effects of aspirin in 116 patients was carried out. The antiplatelet effects of aspirin are associated with impaired renal function. The optimal antithrombotic regimen in CKD patients must be investigated on a larger scale.
  
  
  BACKGROUND
  The pharmacodynamic response to aspirin varies significantly between individuals. Insufficient antiplatelet effects of aspirin are associated with increased risk of ischemic events. Chronic kidney disease (CKD) is suggested to affect the pharmacodynamic response to antiplatelet medication. High on-treatment platelet reactivity (HTPR) to clopidogrel has been reported to partially account for the enhanced risk of death and cardiovascular events in CKD patients. Objective To investigate the antiplatelet effects of aspirin in patients with CKD.
  
  
  METHODS
  We conducted a cross-sectional study in 116 patients on permanent aspirin medication. The pharmacodynamic response to aspirin was determined by arachidonic acid-induced thromboxane formation.
  
  
  RESULTS
  HTPR to aspirin was more frequent in patients with impaired renal function (47% vs. 22%; odds ratio, 3.16; 95% confidence interval [CI], 1.34-7.41; P = 0.008). The pharmacodynamic response to aspirin was impaired in patients with moderate/severe CKD (92; interquartile range [IQR], 282 ng mL(-1) ) as compared to patients with normal/mildly reduced renal function (36; IQR, 100 ng mL(-1) ; difference in medians, 57; CI, 5-110 ng mL(-1) ; P = 0.013). Bivariate Pearson analysis showed residual thromboxane formation to be correlated with glomerular filtration rate (R = -0.303; R(2) = 0.092; P = 0.001). Patients with CKD were older and more frequently female. Multivariate linear regression analysis revealed that the correlation was independent of age (R = -0.314; R(2) = 0.082; P = 0.002) and gender (R = -0.305; R(2) = 0.077; P = 0.006).
  
  
  CONCLUSIONS
  Renal function is correlated with pharmacodynamic response to aspirin. Patients with CKD have an increased risk of impaired antiplatelet effects of aspirin. Larger trials are needed to assess the clinical impact of this finding and investigate the optimal antithrombotic regimen in CKD patients.
authors.affiliation: Division of Cardiology, Pulmonology and Vascular Medicine, Heinrich Heine University Medical Center Dusseldorf, Dusseldorf, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Polzin
authors.affiliation: Division of Cardiology, Pulmonology and Vascular Medicine, Heinrich Heine University Medical Center Dusseldorf, Dusseldorf, Germany.
authors.forename: L
authors.initials: L
authors.lastname: Dannenberg
authors.affiliation: Division of Cardiology, Pulmonology and Vascular Medicine, Heinrich Heine University Medical Center Dusseldorf, Dusseldorf, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Sansone
authors.affiliation: Institute of Pathophysiology, West German Heart and Vascular Center, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
authors.forename: B
authors.initials: B
authors.lastname: Levkau
authors.affiliation: Division of Cardiology, Pulmonology and Vascular Medicine, Heinrich Heine University Medical Center Dusseldorf, Dusseldorf, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Kelm
authors.affiliation: Institute for Pharmacology and Clinical Pharmacology, Heinrich Heine University, Dusseldorf, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Hohlfeld
authors.affiliation: Division of Cardiology, Pulmonology and Vascular Medicine, Heinrich Heine University Medical Center Dusseldorf, Dusseldorf, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Zeus
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D016718:Arachidonic Acid; D001241:Aspirin / Q000627:therapeutic use*; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000097:blood / Q000209:etiology / Q000517:prevention & control*; D003430:Cross-Sectional Studies; D004351:Drug Resistance; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D007668:Kidney / Q000503:physiopathology*; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D010979:Platelet Function Tests; D011237:Predictive Value of Tests; D051436:Renal Insufficiency, Chronic / Q000097:blood / Q000150:complications / Q000175:diagnosis / Q000503:physiopathology*; D012307:Risk Factors; D012720:Severity of Illness Index; D013931:Thromboxanes / Q000378:metabolism
chemical_list: D010975:Platelet Aggregation Inhibitors; D013931:Thromboxanes; D016718:Arachidonic Acid; D001241:Aspirin
keywords: aspirin; chronic kidney disease; drug resistance; platelet activation; platelet function