Antiplatelet effects of aspirin in chronic kidney disease patients

Abstract

EssentialsChronic 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. Summary. 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 crosssectional 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 À1) as compared to patients with normal/mildly reduced renal function (36; IQR, 100 ng mL À1; difference in medians, 57; CI, 5-110 ng mL À1; P = 0.013). Bivariate Pearson analysis showed residual thromboxane formation to be correlated with glomerular filtration rate (R = À0.303; 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 = À0.314; R 2 = 0.082; P = 0.002) and gender (R = À0.305; R 2 = 0.077; P = 0.006). Conclusion: 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.

Role of Dipyrone in the High On-Treatment Platelet Reactivity amongst Acetylsalicylic Acid-Treated Patients Undergoing Peripheral Artery Revascularisation

“…Our results did not show any correlation between the administration of proton pump inhibitors, higher BMI values, diabetes mellitus, and chronic kidney disease – which have been reported to be risk factors for the development of HTPR on ASA treatment [23, 31-33] – and LTA or impedance aggregometry results. This is probably caused by the small number of subjects in our study.…”

Malondialdehyde Assay in the Evaluation of Aspirin Antiplatelet Effects

“…enosine diphosphate receptor blockers, but recent data negated a correlation [27,28]. Further factors that are associated with HTPR to aspirin are enhanced platelet turnover, genetic polymorphisms, patient attributed incompliance and comorbidities like chronic kidney disease or diabetes [5,21,29]. Many tests are available to evaluate aspirin antiplatelet effects [6].…”

“…Impaired aspirin antiplatelet effects are defined as high on-treatment platelet reactivity (HTPR) to aspirin. Enhanced platelet turnover, drugdrug interactions, genetic polymorphisms and comorbidities like diabetes or chronic kidney disease have been identified as associated factors [3][4][5].…”

Thromboxane Formation Assay to Identify High On-Treatment Platelet Reactivity to Aspirin

“…Therefore, the measurement of TX formation is the pharmacologic most specific assay to evaluate platelet inhibition by aspirin. Different studies have now applied the measurement of TXB2 formation in the evaluation of aspirin antiplatelet effects [4,6,17]. However, a consensual cut-off level in the definition of HTPR to aspirin has not been reported.…”

“…Insufficient response is defined as high on-treatment platelet reactivity (HTPR) [3]. Several factors are known to be associated with impaired pharmacodynamic response to antiplatelet medication, like drug-drug interactions, genetic polymorphisms, enhanced platelet turnover, incompliance to medication, and comorbidities like chronic kidney disease or diabetes [4,5,6]. HTPR to aspirin results in worsened clinical outcome and in a higher risk of major adverse cardiac and cerebrovascular events [7].…”