Effect of eptifibatide for acute coronary syndromes: rapid versus late administration--therapeutic yield on platelets (The EARLY Platelet Substudy).
(Clinical Trial;Journal Article)
BACKGROUND: Receptors other than GP IIb/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 micromol/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 IIb/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 IIb/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.
Gurbel, PA; Galbut, B; Bliden, KP; Bahr, RD; Roe, MT; Serebruany, VL; Gibler, WB; Christenson, RH; Ohman, EM; EARLY Platelet Substudy,
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