Published Online
on September 8, 2005

A more recent version of this article appeared on October 1, 2005

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Submitted on April 26, 2005
Revised on May 2, 2004
Accepted on May 4, 2005

Effects of Clopidogrel and Aspirin in Combination versus Aspirin Alone on Platelet Activation and Major Receptor Expression in Patients After Recent Ischemic Stroke. For the Plavix Use for Treatment of Stroke (PLUTO-Stroke) Trial

Victor L. Serebruany MD, PhD^*; Alex I. Malinin MD; Wendy Ziai MD; Alex N. Pokov MD; Deepak L. Bhatt MD; Mark J. Alberts MD; and Dan F. Hanley MD

From the HeartDrug Research Laboratories (V.L.S., A.I.M., A.N.P.), Towson, Md; Johns Hopkins University (W.Z., D.F.H.), Baltimore, Md; Cleveland Clinic (D.L.B.), Cleveland, Ohio; and Northwestern University (M.J.A.), Chicago, Ill.

^* To whom correspondence should be addressed. E-mail: Heartdrug{at}aol.com.

Background and Purpose--Clopidogrel is widely used in patients after recent ischemic stroke; however, its ability to yield additional antiplatelet protection on top of aspirin has never been explored in a controlled study. To determine whether clopidogrel with aspirin (C+ASA) will produce more potent platelet inhibition than aspirin alone (ASA) in patients after ischemic stroke, we conducted the Plavix Use for Treatment of Stroke trial.

Methods--Seventy patients after ischemic stroke were randomly assigned to C+ASA or ASA groups. Platelet studies included aggregometry; cartridge-based analyzers; expression of PECAM-1, P-selectin, GP IIb/IIIa (antigen and activity), vitronectin receptor, and formation of platelet-leukocyte microparticles by flow cytometry. Platelet tests were performed at baseline and after 30 days after randomization.

Results--There were no deaths, hospitalizations, or serious adverse events. There were no differences in the baseline platelet characteristics between C+ASA and ASA groups, or significant changes in platelet parameters in the ASA group, except diminished collagen-induced aggregation (P=0.001). In contrast, therapy with C+ASA resulted in a significant inhibition of platelet activity assessed by ADP- (P=0.00001) and collagen-induced (P=0.02) aggregation; closure time prolongation (P=0.03), and reduction of platelet activation units with Ultegra (P=0.00001); expression of PECAM-1 (P=0.01), and GP IIb/IIIa activity with PAC-1 (P=0.02) when compared with ASA group. Therapy with C+ASA also resulted in the reduced formation of platelet-leukocyte microparticles (P=0.02).

Conclusion--Treatment with C+ASA for 1 month provides significantly greater inhibition of platelet activity than ASA alone in patients after recent ischemic stroke in the frame of the small randomized trial.

Key words: aspirin • clinical trial • clopidogrel • platelets • stroke

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