Effect of eptifibatide for acute coronary syndromes: Rapid versus late administration - Therapeutic yield on platelets (The EARLY platelet substudy)

Paul A. Gurbel, Brian Galbut, Kevin P. Bliden, Raymond D. Bahr, Matthew T. Roe, Victor L. Serebruany, W. Brian Gibler, Robert H. Christenson, E. Magnus Ohman

Research output: Contribution to journalArticle

Abstract

Background: Receptors other than GP Ilb/IIIa may mediate leukocyte-platelet-endothelial interactions that obstruct the microvasculature in acute coronary syndromes (ACS) and cause microinfarcts. The effect of eptifibatide on these receptors was investigated in a substudy of the EARLY Trial. Methods: Patients received early (in the Emergency Department, n = 27) or late (12-24 h, n = 28) eptifibatide. Ten platelet receptors by flow cytometry and platelet aggregation (10 μmol/L ADP) were measured serially at baseline, and at 3, 6, 12 and 24 h after randomization. Results: Platelet aggregation was rapidly inhibited by early eptifibatide therapy (baseline, 72 +/- 20%; 3 h post, 7 +/- 9%; p < 0.001). No significant differences were seen in either group for CD 31, CD 63, CD 107a, CD 107b, CD 41 (GPIIb/IIIa expression), or CD 62p. Leukocyte-platelet aggregate formation (mean fluorescense intensity) trended upward after presentation (early baseline, 43.1 +/- 26.0 versus 65.8 +/- 35.6, p=.09). PAC-1 (GP Ilb/IIIa activity), CD 51/61 (vitronectin receptor) and CD 42b (GP Ib) were inhibited by eptifibatide (p < .05). Conclusions: In Emergency Department patients with unstable angina, early eptifibatide rapidly and profoundly inhibits platelet aggregation and reduces GP Ilb/IIIa activity and the expression of CD51/61 and CD 42b; the latter two effects may also contribute to the drug's anti-thrombotic effect. However, platelet-leukocyte aggregate formation, a marker of platelet activity rises within 24 h after presentation despite eptifibatide therapy and is a potential mechanism for microvascular obstruction.

Original languageEnglish (US)
Pages (from-to)213-219
Number of pages7
JournalJournal of Thrombosis and Thrombolysis
Volume14
Issue number3
DOIs
StatePublished - Dec 1 2002

Keywords

  • Antiplatelet therapy
  • Eptifibatide
  • Platelet receptors
  • Platelets

ASJC Scopus subject areas

  • Hematology
  • Cardiology and Cardiovascular Medicine

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    Gurbel, P. A., Galbut, B., Bliden, K. P., Bahr, R. D., Roe, M. T., Serebruany, V. L., Gibler, W. B., Christenson, R. H., & Ohman, E. M. (2002). Effect of eptifibatide for acute coronary syndromes: Rapid versus late administration - Therapeutic yield on platelets (The EARLY platelet substudy). Journal of Thrombosis and Thrombolysis, 14(3), 213-219. https://doi.org/10.1023/A:1025048726396