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24-01-2010 | Cardiology | Article

Endothelial dysfunction linked to clopidogrel resistance pre-PCI

Abstract

Free abstract

MedWire News: Impaired endothelial function in angina patients awaiting percutaneous coronary intervention (PCI) appears to be associated with heightened platelet reactivity after loading clopidogrel, study findings show.

This link might explain the unfavorable PCI outcomes in patients with more severe endothelial impairment, researcher Emanuele Barbato (OLV Hospital, Aalst, Belgium) and colleagues speculate.

Antiplatelet therapy with aspirin and clopidogrel is indicated for patients undergoing PCI; however, up to 21% of patients show high residual platelet reactivity resulting in increased risk for cardiovascular events.

Several mechanisms have been suggested to explain this, including genetic, cellular, and clinical factors. Notably, greater platelet reactivity has recently been reported in the presence of more severe peripheral vascular atherosclerosis.

In the present study, the researchers tested the hypothesis that impaired peripheral endothelial function - an early marker of vascular atherosclerosis – correlates with platelet reactivity after the administration of clopidogrel.

They recruited 52 consecutive patients with stable angina (66% men), aged an average of 68 years, who were undergoing elective PCI.

Peripheral endothelial function was assessed using endothelial pulse amplitude tonometry (yielding an Endoscore) and von Willebrand factor (vWF) antigen level.

Baseline platelet reactivity was assessed by soluble P-selectin. Patients then received a 600-mg clopidogrel loading dose around 12 hours before PCI. A blood sample was taken just before the procedure to assess platelet reactivity using the point-of-care VerifyNow P2Y12 assay.

The researchers found that the Endoscore was inversely correlated with vWF antigen activity and soluble P-selectin concentration, suggesting greater baseline platelet reactivity with increased impaired endothelial function.

Furthermore, after clopidogrel, the Endoscore correlated directly with the percentage of P2Y12 inhibition, suggesting greater residual platelet reactivity with more impaired endothelial function.

“We can speculate that the greater vWF activity observed in patients with more impaired endothelial function might increase platelet adhesion and aggregation, predisposing to a thrombotic status eventually responsible for the distal microcirculatory embolism and myonecrosis observed during PCI,” Barbato and colleagues comment.

MedWire (www.medwire-news.md) is an independent clinical news service provided by Current Medicine Group, a trading division of Springer Healthcare Limited. © Springer Healthcare Ltd; 2010

By Andrew Czyzewski

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