Impact of Chronic Kidney Disease on Platelet Function Profiles in Diabetes Mellitus Patients With Coronary Artery Disease Taking Dual Antiplatelet Therapy

Angiolillo, Dominick J.; Bernardo, Esther; Capodanno, Davide; Vivas, David; Sabaté, Manel; Ferreiro, José Luis; Ueno, Masashi; Jimenez-Quevedo, Pilar; Alfonso, Fernándo; Bass, Theodore A.; Macaya, Carlos; Fernández‐Ortíz, Antonio

doi:10.1016/j.jacc.2009.10.043

Cited by 200 publications

(125 citation statements)

References 51 publications

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“…The lower quartile identified patients with HRPR 20. As Figure 5 showed, patients with OSA were more likely to have HRPR than those non‐OSA (33.8% versus 13.6%, P =0.012).…”

Section: Resultsmentioning

confidence: 97%

Impact of Obstructive Sleep Apnea on Platelet Function Profiles in Patients With Acute Coronary Syndrome Taking Dual Antiplatelet Therapy

Gong

Xiao

Fan

et al. 2018

JAHA

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BackgroundObstructive sleep apnea (OSA) is a novel risk factor for acute coronary syndrome (ACS). Several studies have shown OSA to be associated with induced platelet reactivity. However, whether OSA have effects on platelet function profiles in ACS patients taking dual antiplatelet therapy remains unexplored.Methods and ResultsThis was a cross‐sectional observational study, in which ACS patients taking maintenance aspirin and clopidogrel therapy were included. OSA was defined as an apnea‐hypopnea index ≥15 events/hour. The inhibitory rate of arachidonic acid or adenosine diphosphate pathway were assessed with thrombelastography and defined patients with high residual on‐treatment platelet reactivity. Platelet indices were obtained from routine analysis of blood samples using an automated blood cell counter. A total of 127 ACS patients taking dual antiplatelet therapy were analyzed. Platelet volume indices, including mean platelet volume and platelet large cell ratio, were significantly increased in patients with OSA. Patients with OSA (n=68) had significantly lower inhibitory rate of adenosine diphosphate receptor pathway (P=0.028) compared with those without (n=59). After adjustment for potential confounders, patients with OSA were more likely to have high residual on‐treatment platelet reactivity after clopidogrel therapy (adjusted odds ratio: 3.25, 95% confidence interval: 1.19–8.87, P=0.021).ConclusionsIn ACS patients taking dual antiplatelet therapy, OSA is associated with an increased level of platelet volume indices, reduced clopidogrel‐induced antiplatelet effects and a greater prevalence of high residual on‐treatment platelet reactivity.

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“…The lower quartile identified patients with HRPR 20. As Figure 5 showed, patients with OSA were more likely to have HRPR than those non‐OSA (33.8% versus 13.6%, P =0.012).…”

Section: Resultsmentioning

confidence: 97%

Impact of Obstructive Sleep Apnea on Platelet Function Profiles in Patients With Acute Coronary Syndrome Taking Dual Antiplatelet Therapy

Gong

Xiao

Fan

et al. 2018

JAHA

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“…The current study is the first to report such an association in the brain. Previous reports have evaluated patients with coronary artery disease or peripheral artery disease (20)(21)(22). For example, Park et al (20) investigated patients who underwent coronary angiography, coronary vascular intervention or peripheral vascular intervention and measured platelet aggregation using the VerifyNow P2Y12 Assay in 23 normal renal function patients receiving 75 mg/ day of clopidogrel, 18 CKD patients receiving 75 mg/day of clopidogrel and 18 CKD patients receiving 150 mg/day of clopidogrel.…”

Section: Discussionmentioning

confidence: 99%

Response to Clopidogrel and Its Association with Chronic Kidney Disease in Noncardiogenic Ischemic Stroke Patients

et al. 2014

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Objective Noncardiogenic ischemic stroke patients with chronic kidney disease (CKD) are known to have a greater rate of ischemic stroke recurrence than those without. Although clopidogrel is often used to prevent the recurrence of noncardiogenic ischemic stroke, the relationship between the response to clopidogrel and CKD is unclear. In the present study, the relationship between the response to clopidogrel and the presence of CKD was investigated in noncardiogenic ischemic stroke patients. Methods A total of 129 noncardiogenic ischemic stroke patients receiving 75 mg/day of clopidogrel for ! 1 week were evaluated. The VerifyNow P2Y12 Assay was used to measure the level of platelet aggregation induced by 20 μM of adenosine diphosphate, and the degree of platelet aggregation and frequency of clopidogrel resistance were compared between 34 patients with CKD and 95 patients without CKD. Clopidogrel resistance was defined as a P2Y12 Reaction Units (PRU) value of >230 and/or % inhibition <20%. Results The PRU value was 201.9±91.3 in the patients with CKD and 163.3±86.4 in the patients without CKD (p=0.035). The frequency of a PRU value of >230 was 44.1% (15 patients) among the patients with CKD and 17.9% (17 patients) among those without CKD (p=0.002). The percent inhibition was 29.9%± 28.1% among the patients with CKD and 41.1%±28.0% among the patients without CKD (p=0.030). The frequency of % inhibition <20% was 47.1% (16 patients) among the patients with CKD and 26.3% (25 patients) among those without CKD (p=0.026). Conclusion The present study showed that noncardiogenic ischemic stroke patients with CKD have a greater frequency of clopidogrel resistance, thus suggesting that the response to clopidogrel is diminished in these patients.

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“…In another crossover study, the addition of aspirin (325 mg daily) to cilostazol (100 mg twice a day) did not enhance the inhibition of AAinduced platelet aggregation compared with cilostazol alone (p = 0.38) 30) , implying the potential inhibition by cilostazol of thromboxane receptor-mediated platelet aggregation. Recent studies have also demonstrated that patients with high platelet reactivity (HPR) to multiple agonists are more susceptible to clinical events than those with HPR to any isolated agonists 31,32) . Therefore, the pharmacodynamic effects and clinical benefits of adjunctive cilostazol may be underestimated when ADP is used as the sole platelet agonist to evaluate the platelet function.…”

Section: Discussionmentioning

confidence: 99%

Pharmacodynamic Effects of Cilostazol Versus Clopidogrel in Stented Patients under Proton Pump Inhibitor Co-administration: The ACCEL-PARAZOL Study

Park¹,

Jung²,

Tantry³

et al. 2014

JAT

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Aim: Proton pump inhibitor (PPI) therapy has been shown to attenuate the antiplatelet effects of clopidogrel. The aim of this study was to compare the antiplatelet effects of cilostazol versus clopidogrel in patients co-administered a PPI. Methods: We enrolled PPI-naïve stented patients treated with standard clopidogrel and aspirin therapy for at least six months (n = 100). The patients were randomly assigned to receive either cilostazol at a dose of 100 mg twice daily (CILO group) or clopidogrel at a dose of 75 mg daily (CLPD group) in addition to lansoprazole (30 mg daily). The platelet aggregation (PA) determined using light transmittance aggregometry and the platelet reactivity index (PRI) obtained using a vasodilator-stimulated phosphoprotein phosphorylation assay were measured before randomization and at the 14-day follow-up visit. The primary endpoint was the PRI value at follow-up. Results: At follow-up, the CLPD group showed similar values of PRI as the CILO group (66.9±14.0% vs. 63.1±14.1%; mean difference: 3.9%; 95% confidence interval of difference: −1.7% to 9.4%; p=0.174). However, the 6 μg/mL collagen-and 0.5 mg/mL arachidonic acid-induced PA values in the CLPD group were higher than those observed in the CILO group (mean differences: 9.8% to 11.1%; all p values ＜0.001). CYP2C19 loss-of-function allele carriage was the major contributing factor associated with the PRI level in the absence of lansoprazole treatment (with a gene-dose effect); this association was not observed in the subjects receiving lansoprazole co-administration in the CLPD group. Conclusions: During lansoprazole co-administration, cilostazol treatment achieves a more favorable platelet function profile than clopidogrel therapy. The use of combination treatment with cilostazol and aspirin deserves further attention with respect to the management of stable stented patients requiring PPI co-administration. IntroductionDual antiplatelet therapy (DAPT) with clopidogrel and aspirin has been shown to reduce major cardiovascular events following percutaneous coronary intervention (PCI) or acute coronary syndrome (ACS). However, the risk of gastrointestinal (GI) Park Y and Jung JM contributed equally to this work. cilostazol compared with that of ADP P2Y12 receptor blockers and the findings of a previous report of healthy subjects showing relatively lower inhibitory effects of ADP-mediated platelet aggregation by cilostazol than with clopidogrel 18) may limit its clinical application in stented patients. Since cilostazol is also metabolized by the CYP2C19 enzyme 19) , the CYP2C19 genetic polymorphism and/or concomitant use of a PPI may influence its pharmacodynamic effect.In the current study, we therefore evaluated the influence of lansoprazole administration on the effects of clopidogrel and compared the pharmacodynamic actions of cilostazol vs. clopidogrel treatment during PPI co-administration in patients with a history of coronary stenting. Methods Patient Selection and Study DesignThis ACCEL-PARAZOL (phArmacodynamic effect of Cilos...

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Impact of Chronic Kidney Disease on Platelet Function Profiles in Diabetes Mellitus Patients With Coronary Artery Disease Taking Dual Antiplatelet Therapy

Abstract: 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.

Cited by 200 publications

References 51 publications

Impact of Obstructive Sleep Apnea on Platelet Function Profiles in Patients With Acute Coronary Syndrome Taking Dual Antiplatelet Therapy

Impact of Obstructive Sleep Apnea on Platelet Function Profiles in Patients With Acute Coronary Syndrome Taking Dual Antiplatelet Therapy

Response to Clopidogrel and Its Association with Chronic Kidney Disease in Noncardiogenic Ischemic Stroke Patients

Pharmacodynamic Effects of Cilostazol Versus Clopidogrel in Stented Patients under Proton Pump Inhibitor Co-administration: The ACCEL-PARAZOL Study

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