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Journal of Cardiovascular Pharmacology:
doi: 10.1097/FJC.0000000000000057
Original Article

Effects of Clopidogrel Therapy on Oxidative Stress, Inflammation, Vascular Function, and Progenitor Cells in Stable Coronary Artery Disease

Ramadan, Ronnie MD*; Dhawan, Saurabh S. MD*; Syed, Hamid MD*; Pohlel, F. Khan*; Binongo, Jose N. G. PhD; Ghazzal, Ziyad B. MD; Quyyumi, Arshed A. MD*

Supplemental Author Material
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Background: Traditional cardiovascular risk factors lead to endothelial injury and activation of leukocytes and platelets that initiate and propagate atherosclerosis. We proposed that clopidogrel therapy in patients with stable coronary artery disease imparts a pleiotropic effect that extends beyond antiplatelet aggregation to other atheroprotective processes.

Methods: Forty-one subjects were randomized in a double-blind, placebo-controlled, crossover study to receive either clopidogrel 75 mg daily or placebo for 6 weeks and then transitioned immediately to the other treatment for an additional 6 weeks. We assessed (1) endothelial function as flow-mediated dilation of the brachial artery, (2) arterial stiffness and central augmentation index using applanation tonometry, (3) vascular function as fingertip reactive hyperemia index, (4) inflammation by measuring plasma CD40 ligand and serum high-sensitivity c-reactive protein levels, (5) oxidative stress by measuring plasma aminothiols, and (6) circulating progenitor cells, at baseline and at the end of each 6-week treatment period.

Results: Clopidogrel therapy resulted in a significant reduction in soluble CD40 ligand (P = 0.03), a prothrombotic and proinflammatory molecule derived mainly from activated platelets. However, clopidogrel therapy had no effect on endothelial function, arterial stiffness, inflammatory and oxidative stress markers, or progenitor cells.

Conclusions: Our findings suggest a solitary antiplatelet effect of clopidogrel therapy in patients with stable coronary artery disease, with no effect on other subclinical markers of cardiovascular disease risk.

© 2014 by Lippincott Williams & Wilkins.

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