Abstract | BACKGROUND: METHODS: Patients with left ventricular ejection fraction <40%, or CHF symptoms in the setting of preserved systolic function and New York Heart Association class II-IV were screened. Patients were considered to have platelet activation when 4 of the following 5 parameters were met: ADP-induced platelet aggregation >60%; collagen-induced aggregation >70%; whole blood aggregation >18 ohms; expression of GP IIb/IIIa >220 log MFI; and P-selectin cell positivity >8%. All patients were treated with 325 mg of acetylsalycilic acid (ASA) for at least 1 month. Patients receiving an antithrombotic agent other than ASA were excluded. Patients meeting clinical and laboratory criteria were randomly assigned to C+A (n=25), A (n=25) groups, or represent screen failures (n=38). Platelet studies (conventional and whole blood aggregometry, shear-induced activation, expression of 10 major receptors and formation of platelet-leukocyte microparticles) were performed at baseline and after 30 days of therapy. RESULTS: There were no deaths, hospitalizations, or serious adverse events. There were no changes in platelet parameters in the A group. In contrast, therapy with C+A resulted in a significant inhibition of platelet activity assessed by ADP-induced (P =.00001), and epinephrine-induced (P =.0016) aggregation, closure time (P =.04), expression of PECAM-1 (P =.009), GP Ib (P =.006), GP IIb/IIIa antigen (P =.0001), GP IIb/IIIa activity with PAC-1 (P =.0021), and CD151 (P =.0026) when compared with the A group. Therapy with C+A also resulted in the reduced formation of platelet-leukocyte microparticles (P =.021). Collagen-induced aggregation in plasma and in whole blood, expression of vitronectin receptor, P-selectin, CD63, CD107a, and CD107b did not differ among groups. CONCLUSIONS: Treatment with C+A for 1 month provides significantly greater inhibition of platelet activity than ASA alone in patients with CHF. Patients with CHF with heightened platelet activity represent a potential target population in which addition of clopidogrel may decrease mortality rates by reducing the incidence of thrombotic vascular events.
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Authors | Victor L Serebruany, Alex I Malinin, Scott D Jerome, David R Lowry, Athol W Morgan, David C Sane, Jean-François Tanguay, Steven R Steinhubl, Christopher M O'connor |
Journal | American heart journal
(Am Heart J)
Vol. 146
Issue 4
Pg. 713-20
(Oct 2003)
ISSN: 1097-6744 [Electronic] United States |
PMID | 14564328
(Publication Type: Clinical Trial, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
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Chemical References |
- Platelet Aggregation Inhibitors
- Platelet Glycoprotein GPIIb-IIIa Complex
- Clopidogrel
- Ticlopidine
- Aspirin
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Topics |
- Aged
- Aspirin
(therapeutic use)
- Clopidogrel
- Drug Therapy, Combination
- Female
- Flow Cytometry
- Heart Failure
(blood, drug therapy)
- Humans
- Male
- Middle Aged
- Platelet Activation
(drug effects)
- Platelet Aggregation
(drug effects)
- Platelet Aggregation Inhibitors
(therapeutic use)
- Platelet Glycoprotein GPIIb-IIIa Complex
(immunology)
- Statistics as Topic
- Ticlopidine
(analogs & derivatives, therapeutic use)
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