Impact of Pentoxifylline on Platelet Function Profiles in Patients With Type 2 Diabetes Mellitus and Coronary Artery Disease on Dual Antiplatelet Therapy With Aspirin and Clopidogrel

Ueno, Masashi; Ferreiro, José Luis; Tomasello, Salvatore D.; Tello‐Montoliu, Antonio; Capodanno, Davide; Seecheran, Naveen; Kodali, Murali; Dharmashankar, Kodlipet; Desai, Bhaloo; Charlton, Ronald K.; Bass, Theodore A.; Angiolillo, Dominick J.

doi:10.1016/j.jcin.2011.05.016

Cited by 18 publications

(9 citation statements)

References 45 publications

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“…There are also multiple reports of the use of % inhibition. For this study, clopidogrel resistance was defined as a PRU value >230 (12)(13)(14) and/or % inhibition <20% (15)(16)(17). …”

Section: Definition Of Clopidogrel Resistancementioning

confidence: 99%

Relationship between Smoking and Responsiveness to Clopidogrel in Non-cardiogenic Ischemic Stroke Patients

et al. 2014

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Objective Clopidogrel is used to prevent the recurrence of non-cardiogenic ischemic stroke, but individual responsiveness to the drug varies. Moreover, it is known that smoking, which is a risk factor for ischemic stroke, affects the drug's pharmacokinetics. The objective of the present study was to investigate a possible relationship between smoking and responsiveness to clopidogrel in non-cardiogenic ischemic stroke patients. Methods The study involved 209 non-cardiogenic ischemic stroke patients who were administered oral clopidogrel at a dosage of 75 mg/day for at least 1 week. Platelet aggregation in response to adenosine diphosphate (20 μM) was measured in each patient using the VerifyNow P2Y12 Assay. Platelet aggregation and the incidence of resistance to clopidogrel were compared between a smokers group (70 patients) and a non-smokers group (139 patients). Clopidogrel resistance was defined as a P2Y12 Reaction Units (PRU) value >230 and/or % inhibition <20%. Results The mean PRU was 128.3±85.5 in the smokers group and 167.7±86.6 in the non-smokers group (p=0.002). The incidence of PRU >230 was 12.9% (9 patients) in the smokers group and 25.9% (36 patients) in the non-smokers group (p=0.033). The mean % inhibition was 48.6±30.7% in the smokers group and 36.9±27.6% in the non-smokers group (p=0.009). The incidence of patients with % inhibition <20% was 24.3% (17 patients) in the smokers group and 34.5% (48 patients) in the non-smokers group (p=0.155). Conclusion The incidence of clopidogrel resistance was lower in the non-cardiogenic ischemic stroke patients who were smokers, thus indicating that these patients' responsiveness to this drug may be enhanced.

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“…There are also multiple reports of the use of % inhibition. For this study, clopidogrel resistance was defined as a PRU value >230 (12)(13)(14) and/or % inhibition <20% (15)(16)(17). …”

Section: Definition Of Clopidogrel Resistancementioning

confidence: 99%

Relationship between Smoking and Responsiveness to Clopidogrel in Non-cardiogenic Ischemic Stroke Patients

et al. 2014

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“…There are also several reports that used the % inhibition as an indicator. In the present study, clopidogrel resistance was defined as PRU >230 (14)(15)(16) and/or % inhibition <20% (17)(18)(19), based on previous reports.…”

Section: Definition Of Clopidogrel Resistancementioning

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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“…Whole blood was collected in hirudin treated tubes and, following 50% dilution with saline, MEA was performed with the Multiplate analyzer (Dynabyte Medical, Munich, Germany) as previously described (21,22). This instrument assesses the change in impedance caused by the adhesion of platelets onto sensor units composed of silver-covered electrodes.…”

Section: Multiple Electrode Aggregometry (Mea)mentioning

confidence: 99%

Impact of aspirin dose on adenosine diphosphate-mediated platelet activities

Tello‐Montoliu¹,

Thano²,

Rollini³

et al. 2013

Thromb Haemost

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Different aspirin dosing regimens have been suggested to impact outcomes when used in combination with adenosine diphosphate (ADP) P2Y12 receptor antagonists. Prior investigations have shown that not only aspirin, but also potent ADP P2Y12 receptor blockade can inhibit thromboxane A2-mediated platelet activation. The impact of aspirin dosing on ADP mediated platelet activities is unknown and represents the aim of this in vitro pilot pharmacodynamic (PD) investigation. Twenty-six patients with stable coronary artery disease on aspirin 81 mg/day and P2Y12 naïve were enrolled. PD assessments were performed at baseline, while patients were on 81 mg/day aspirin and after switching to 325 mg/day for 7 ± 2 days with and without escalating concentrations (vehicle, 1, 3, and 10 μM) of prasugrel's active metabolite (P-AM). PD assays included flow cytometric assessment of VASP to define the platelet reactivity index (PRI) and the Multiplate Analyzer (MEA) using multiple agonists [ADP, ADP + prostaglandin (PGE1), arachidonic acid (AA), and collagen]. Escalating P-AM concentrations showed incremental platelet P2Y12 inhibition measured by VASP-PRI (p<0.001). However, there were no differences according to aspirin dosing regimen at any P-AM concentration (vehicle: p=0.899; 1 μM: p=0.888; 3 μM: p=0.524; 10 μM: p=0.548). Similar findings were observed in purinergic markers assessed by MEA (ADP and ADP+PGE1). P-AM addition significantly reduced AA and collagen induced platelet aggregation (p<0.001 for all measures), irrespective of aspirin dose. In conclusion, aspirin dosing does not appear to affect PD measures of ADP-mediated platelet reactivity irrespective of the degree of P2Y12 receptor blockade. P2Y12 receptor blockade modulates platelet reactivity mediated by alternative activators.

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Impact of Pentoxifylline on Platelet Function Profiles in Patients With Type 2 Diabetes Mellitus and Coronary Artery Disease on Dual Antiplatelet Therapy With Aspirin and Clopidogrel

Abstract: Adjunctive treatment with pentoxifylline is not associated with increased platelet inhibitory effects in DM patients with coronary artery disease receiving DAPT.

Cited by 18 publications

References 45 publications

Relationship between Smoking and Responsiveness to Clopidogrel in Non-cardiogenic Ischemic Stroke Patients

Relationship between Smoking and Responsiveness to Clopidogrel in Non-cardiogenic Ischemic Stroke Patients

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

Impact of aspirin dose on adenosine diphosphate-mediated platelet activities

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