Dipstick proteinuria is an independent predictor of high on treatment platelet reactivity in patients on clopidogrel, but not aspirin, admitted for major adverse cardiovascular events

Davila, Carlos D.; Vargas, Fernando; Huang, Kuan-Hsiang Gary; Monaco, Thomas J.; Dimou, Anastasios; Rangaswami, Janani; Figueredo, Vincent M.

doi:10.3109/09537104.2014.971000

Cited by 9 publications

(9 citation statements)

References 34 publications

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“…This instrument measures light transmittance as aggregation occurs, and data are converted into ARU or PRU. High on-treatment platelet reactivity (HTPR) is associated with worse outcomes, and HTPR was defined as PRUs > 208 for clopidogrel and ARUs > 550 for aspirin [8].…”

Section: Antiplatelet Effect Analysismentioning

confidence: 99%

Plasma miR-142 predicts major adverse cardiovascular events as an intermediate biomarker of dual antiplatelet therapy

Tang

Lei

et al. 2018

Acta Pharmacol Sin

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MicroRNAs (miRNAs) are widely expressed in organisms and are implicated in the regulation of most biological functions. The present study investigated the association of plasma miRNAs with the clinical outcomes of dual antiplatelet therapy in coronary artery disease (CAD) patients who underwent percutaneous coronary intervention (PCI). Plasma miRNA levels were screened using high-throughput Illumina sequencing to evaluate the antiplatelet efficacy of clopidogrel and aspirin. Six plasma miRNAs (miR-126, miR-130a, miR-27a, miR-106a, miR-21, and miR-142) were associated with clopidogrel-treated platelet aggregation. These miRNAs were validated in a prospective cohort of 1230 CAD patients using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). High plasma miR-142 levels were associated with a high risk of major adverse cardiovascular events (MACE), with a hazard ratio (95% confidence interval) of 1.83 (1.30-2.59) at a false discovery rate of <5%. Multivariable Cox regression analysis revealed that diabetes mellitus, heart failure, calcium channel blocker application, and a high plasma miR-142 level were independent risk factors of MACE. The levels of the six plasma miRNAs were not significantly associated with bleeding events during the 3-year follow-up. In conclusion, plasma miR-142 is potential marker to predict MACE in CAD patients after PCI.

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Section: Antiplatelet Effect Analysismentioning

confidence: 99%

Plasma miR-142 predicts major adverse cardiovascular events as an intermediate biomarker of dual antiplatelet therapy

Tang

Lei

et al. 2018

Acta Pharmacol Sin

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“…Impaired renal function is associated with increased mortality and incidence of cardiovascular events . It is known that insufficient P2Y12 inhibition by clopidogrel is more frequent in patients with chronic kidney disease (CKD) . Among other factors, this was reported to account for a worse outcome in CKD patients with coronary artery disease .…”

Section: Introductionmentioning

confidence: 99%

Antiplatelet effects of aspirin in chronic kidney disease patients

Polzin

Dannenberg

Sansone

et al. 2016

Journal of Thrombosis and Haemostasis

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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.

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“…Clopidogrel and aspirin resistance may occur in some dogs, and PFT may aid in determining if such resistance is present. Hypothesized mechanisms for suspected resistance to aspirin or clopidogrel in our study that have been documented in people with renal disease include increased platelet turnover, increased platelet activity (increased fibrinogen, increased tissue factor), changes in the release of ADP and serotonin from platelet granules, and changes in the cytoskeletal arrangement of platelets (eg, glycoprotein IIb/IIIa, thrombin) . For aspirin resistance in people with renal disease, increased inflammation and oxidative stress have been shown to lead to increased concentrations of thromboxane A2 via pathways not inhibited by aspirin .…”

Section: Discussionmentioning

confidence: 57%

“…22,[32][33][34][35][36][37][38][39] Interestingly, a recent study of human patients showed that presence of proteinuria independent of estimated glomerular filtration rate was associated with treatment resistance for clopidogrel, but not aspirin. 40 As mentioned previously, dogs with PLN can progress to CKD, 23,24 which raises concern for potential lack of treatment efficacy in veterinary patients. Objective ways to evaluate for treatment response in humans include PFT and measurement of various drug metabolites, but doing so is not common in veterinary practice.…”

Section: Discussionmentioning

confidence: 98%

“…Hypothesized mechanisms for suspected resistance to aspirin or clopidogrel in our study that have been documented in people with renal disease include increased platelet turnover, increased platelet activity (increased fibrinogen, increased tissue factor), changes in the release of ADP and serotonin from platelet granules, and changes in the cytoskeletal arrangement of platelets (eg, glycoprotein IIb/IIIa, thrombin). 22,32,34,[38][39][40] For aspirin resistance in people with renal disease, increased inflammation and oxidative stress have been shown to lead to increased concentrations of thromboxane A2 via pathways not inhibited by aspirin. 36 Future studies to evaluate the efficacy of these medications in various clinical settings as well as associations with clinical outcome are needed in veterinary medicine.…”

Section: Discussionmentioning

confidence: 99%

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Platelet aggregometry testing during aspirin or clopidogrel treatment and measurement of clopidogrel metabolite concentrations in dogs with protein‐losing nephropathy

Shropshire

Johnson

Olver

2020

Veterinary Internal Medicne

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Background Dogs with protein‐losing nephropathy (PLN) are treated with antiplatelet drugs for thromboprophylaxis but no standardized method exists to measure drug response. It is also unknown if clopidogrel metabolite concentrations [CM] differ between healthy and PLN dogs. Objectives Assess response to aspirin or clopidogrel in PLN dogs using platelet aggregometry (PA) and compare [CM] between healthy and PLN dogs. Animals Six healthy and 14 PLN dogs. Methods Platelet aggregometry using adenosine diphosphate (ADP), arachidonic acid (AA), and saline was performed in healthy dogs at baseline and 1‐week postclopidogrel administration to identify responders or nonresponders. A decrease of ≥60% for ADP or ≥30% for AA at 1 or 3 hours postpill was used to define a responder. At 1 and 3 hours postclopidogrel, [CM] and PA were measured in healthy and PLN dogs. Platelet aggregometry was performed in PLN dogs at baseline, 1, 6, and 12 weeks after clopidogrel or aspirin administration. Results In PLN dogs receiving clopidogrel, PA differed from baseline at all time points for ADP but not for AA at any time point. Most dogs responded at 1 or both time points except for 1 dog that showed no response. For PLN dogs receiving aspirin, no differences from baseline were observed at any time point for either ADP or AA. No differences in [CM] were found at either time point between healthy and PLN dogs. Conclusions and Clinical Importance Platelet aggregometry may represent an objective method to evaluate response to clopidogrel or aspirin treatment and PLN dogs appear to metabolize clopidogrel similarly to healthy dogs.

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Dipstick proteinuria is an independent predictor of high on treatment platelet reactivity in patients on clopidogrel, but not aspirin, admitted for major adverse cardiovascular events

Cited by 9 publications

References 34 publications

Plasma miR-142 predicts major adverse cardiovascular events as an intermediate biomarker of dual antiplatelet therapy

Plasma miR-142 predicts major adverse cardiovascular events as an intermediate biomarker of dual antiplatelet therapy

Antiplatelet effects of aspirin in chronic kidney disease patients

Platelet aggregometry testing during aspirin or clopidogrel treatment and measurement of clopidogrel metabolite concentrations in dogs with protein‐losing nephropathy

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