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.
*Division of Cardiology, Department of Medicine, Emory University School of Medicine, Atlanta, GA;
†Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Atlanta, GA; and
‡Division of Cardiology, Department of Medicine, American University of Beirut, Beirut, Lebanon.
Reprints: Ronnie Ramadan, MD, Division of Cardiology, Department of Medicine, Emory Clinical Cardiovascular Research Institute, 1462 Clifton Road N.E. Suite 507, Atlanta, GA 30322 (e-mail: firstname.lastname@example.org).
The study was funded by an investigator initiated research grant from Sanofi Aventis.
The authors report no conflicts of interest.
ClinicalTrials.gov IDENTIFIER: NCT01283282; URL: http://clinicaltrials.gov/ct2/show/NCT01283282.
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Received June 16, 2013
Accepted November 27, 2013