Clopidogrel results in favourable changes in nitric oxide metabolism in patients undergoing percutaneous coronary intervention

Bundhoo, Shantu; Sagan, Ewelina; James, Philip E.; Anderson, Richard

doi:10.1160/th13-05-0394

Cited by 3 publications

(2 citation statements)

References 11 publications

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“…One group received clopidogrel at a 600 mg loading dose, while the second group was already on a clopidogrel maintenance dose of 75 mg for at least three days. Both loaded patients and chronic therapy patients showed a beneficial trend of the plasma total antioxidant capacity (TAC) [ 156 ].…”

Section: Antioxidant Effects Of Antiplatelet Drugsmentioning

confidence: 99%

Antioxidant Properties of Oral Antithrombotic Therapies in Atherosclerotic Disease and Atrial Fibrillation

et al. 2023

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The thrombosis-related diseases are one of the leading causes of illness and death in the general population, and despite significant improvements in long-term survival due to remarkable advances in pharmacologic therapy, they continue to pose a tremendous burden on healthcare systems. The oxidative stress plays a role of pivotal importance in thrombosis pathophysiology. The anticoagulant and antiplatelet drugs commonly used in the management of thrombosis-related diseases show several pleiotropic effects, beyond the antithrombotic effects. The present review aims to describe the current evidence about the antioxidant effects of the oral antithrombotic therapies in patients with atherosclerotic disease and atrial fibrillation.

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Section: Antioxidant Effects Of Antiplatelet Drugsmentioning

confidence: 99%

Antioxidant Properties of Oral Antithrombotic Therapies in Atherosclerotic Disease and Atrial Fibrillation

et al. 2023

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“…This is consistent with inhibition of platelet aggregation we have observed at these concentrations and with previously established effects of RSNO on platelets. 39 Interestingly, a significant reduction in EV concentration was only seen in the clopidogrel group. Whether this decrease can be attributed to the increased RSNO levels seen compared with the naïve group, or as a result of the combination of two independent effects of NO and clopidogrel, remains unclear.…”

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confidence: 94%

Dietary Nitrate Supplementation Reduces Circulating Platelet-Derived Extracellular Vesicles in Coronary Artery Disease Patients on Clopidogrel Therapy: A Randomised, Double-Blind, Placebo-Controlled Study

et al. 2018

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Extracellular vesicles (EVs) are implicated in the pathogenesis of cardiovascular disease (CVD). Specifically, platelet-derived EVs are highly pro-coagulant, promoting thrombin generation and fibrin clot formation. Nitrate supplementation exerts beneficial effects in CVD, via an increase in nitric oxide (NO) bioavailability. Clopidogrel is capable of producing NO-donating compounds, such as S-nitrosothiols (RSNO) in the presence of nitrite and low pH. The aim of this study was to assess the effect of nitrate supplementation with versus without clopidogrel therapy on circulating EVs in coronary artery disease (CAD) patients. In this randomized, double-blind, placebo-controlled study, CAD patients with ( = 10) or without ( = 10) clopidogrel therapy received a dietary nitrate supplement (SiS nitrate gel) or identical placebo. NO metabolites and platelet activation were measured using ozone-based chemiluminescence and multiple electrode aggregometry. EV concentration and origin were determined using nanoparticle tracking analysis and time-resolved fluorescence. Following nitrate supplementation, plasma RSNO was elevated (4.7 ± 0.8 vs 0.2 ± 0.5 nM) and thrombin-receptor mediated platelet aggregation was reduced (-19.9 ± 6.0 vs 4.0 ± 6.4 U) only in the clopidogrel group compared with placebo. Circulating EVs were significantly reduced in this group (-1.183e ± 3.15e vs -9.93e± 1.84e EVs/mL), specifically the proportion of CD41+ EVs (-2,120 ± 728 vs 235 ± 436 RFU [relative fluorescence unit]) compared with placebo. In vitro experiments demonstrated clopidogrel-SNO can reduce platelet-EV directly (6.209e± 4.074e vs 3.94e ± 1.91e EVs/mL). In conclusion, nitrate supplementation reduces platelet-derived EVs in CAD patients on clopidogrel therapy, increasing patient responsiveness to clopidogrel. Nitrate supplementation may represent a novel approach to moderating the risk of thrombus formation in CAD patients.

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A new mechanism of action of thienopyridine antiplatelet drugs – A role for gastric nitrosthiol metabolism?

2014

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Clopidogrel results in favourable changes in nitric oxide metabolism in patients undergoing percutaneous coronary intervention

Cited by 3 publications

References 11 publications

Antioxidant Properties of Oral Antithrombotic Therapies in Atherosclerotic Disease and Atrial Fibrillation

Antioxidant Properties of Oral Antithrombotic Therapies in Atherosclerotic Disease and Atrial Fibrillation

Dietary Nitrate Supplementation Reduces Circulating Platelet-Derived Extracellular Vesicles in Coronary Artery Disease Patients on Clopidogrel Therapy: A Randomised, Double-Blind, Placebo-Controlled Study

A new mechanism of action of thienopyridine antiplatelet drugs – A role for gastric nitrosthiol metabolism?

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