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Effects of roxifiban on platelet aggregation and major receptor expression in patients with coronary artery disease for the Roxifiban Oral Compound Kinetics Evaluation Trial-I (ROCKET-I Platelet Substudy).

Publication ,  Journal Article
Serebruany, VL; Malinin, AI; O'connor, CM; Gurbel, PA; Roxifiban Oral Compound Kinetics Evaluation Trial-I Platelet Substudy,
Published in: Am Heart J
July 2003

BACKGROUND: It has been expected that therapy with oral glycoprotein (GP) IIb/IIIa blockers including roxifiban will reduce mortality and vascular complications in a long-term. However, platelet-related properties of roxifiban in the clinical setting are not well known. We measured platelet characteristics during chronic treatment in patients with coronary artery disease enrolled in the Roxifiban Oral Compound Kinetics Evaluation Trial (ROCKET-I). METHODS: ROCKET-I was designed as a randomized, double blind, multicenter, dose-ranging study of roxifiban, administered either as monotherapy or concomitantly with aspirin, compared with aspirin alone. Thirty-one patients were assigned for 24 weeks of therapy with aspirin (n = 7), roxifiban (n = 9), or roxifiban plus aspirin (n = 15). Platelets were assessed 5 times in each patient at baseline, and at weeks 2, 4, 12, 18, and 24 thereafter with aggregometry and flow cytometry. RESULTS: Baseline platelet characteristics were similar in all 3 groups. There was a consistent significant decrease of adenosine diphosphate- (P =.0001) and collagen-induced (P =.002) platelet aggregation in the patients treated with roxifiban when compared with patients treated with aspirin alone. Flow cytometry revealed paradoxical late activation of GP IIb/IIIa expression (P =.007) when roxifiban was used without aspirin, which was significant compared with the aspirin and aspirin-roxifiban groups. There were no differences among groups in GP Ib expression, although its rise was more profound in the patients treated with roxifiban. There were substantial differences in the P-selectin expression. Although aspirin time dependently decreased the percent of P-selectin positive platelets (P =.02), treatment with roxifiban resulted in the phasic changes with the early inhibition (P =.01) and then 2-fold activation (P =.0001) starting at week 12 of the therapy. There was an early transient activation of platelet endothelial cell adhesion molecule-1 expression (P =.008) at week 2, followed by the later inhibition of this receptor (P =.003) in patients treated with roxifiban. CONCLUSION: Despite achieving sustained inhibition of platelet aggregation, therapy with roxifiban has been associated with over expression or phasic changes of major platelet receptors. These data may explain clinical concerns about the use of oral GP IIb/IIIa inhibitors linking higher mortality rates and incidence of thrombotic episodes with paradoxical switching to alternative passways of platelet activation.

Duke Scholars

Published In

Am Heart J

DOI

EISSN

1097-6744

Publication Date

July 2003

Volume

146

Issue

1

Start / End Page

91 / 98

Location

United States

Related Subject Headings

  • Thrombolytic Therapy
  • Statistics, Nonparametric
  • Platelet Glycoprotein GPIIb-IIIa Complex
  • Platelet Function Tests
  • Platelet Aggregation
  • Middle Aged
  • Male
  • Isoxazoles
  • Humans
  • Flow Cytometry
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Serebruany, V. L., Malinin, A. I., O’connor, C. M., Gurbel, P. A., & Roxifiban Oral Compound Kinetics Evaluation Trial-I Platelet Substudy, . (2003). Effects of roxifiban on platelet aggregation and major receptor expression in patients with coronary artery disease for the Roxifiban Oral Compound Kinetics Evaluation Trial-I (ROCKET-I Platelet Substudy). Am Heart J, 146(1), 91–98. https://doi.org/10.1016/S0002-8703(03)00186-8
Serebruany, Victor L., Alex I. Malinin, Christopher M. O’connor, Paul A. Gurbel, and Paul A. Roxifiban Oral Compound Kinetics Evaluation Trial-I Platelet Substudy. “Effects of roxifiban on platelet aggregation and major receptor expression in patients with coronary artery disease for the Roxifiban Oral Compound Kinetics Evaluation Trial-I (ROCKET-I Platelet Substudy).Am Heart J 146, no. 1 (July 2003): 91–98. https://doi.org/10.1016/S0002-8703(03)00186-8.
Serebruany VL, Malinin AI, O’connor CM, Gurbel PA, Roxifiban Oral Compound Kinetics Evaluation Trial-I Platelet Substudy. Effects of roxifiban on platelet aggregation and major receptor expression in patients with coronary artery disease for the Roxifiban Oral Compound Kinetics Evaluation Trial-I (ROCKET-I Platelet Substudy). Am Heart J. 2003 Jul;146(1):91–8.
Serebruany VL, Malinin AI, O’connor CM, Gurbel PA, Roxifiban Oral Compound Kinetics Evaluation Trial-I Platelet Substudy. Effects of roxifiban on platelet aggregation and major receptor expression in patients with coronary artery disease for the Roxifiban Oral Compound Kinetics Evaluation Trial-I (ROCKET-I Platelet Substudy). Am Heart J. 2003 Jul;146(1):91–98.
Journal cover image

Published In

Am Heart J

DOI

EISSN

1097-6744

Publication Date

July 2003

Volume

146

Issue

1

Start / End Page

91 / 98

Location

United States

Related Subject Headings

  • Thrombolytic Therapy
  • Statistics, Nonparametric
  • Platelet Glycoprotein GPIIb-IIIa Complex
  • Platelet Function Tests
  • Platelet Aggregation
  • Middle Aged
  • Male
  • Isoxazoles
  • Humans
  • Flow Cytometry