TY - JOUR
T1 - Effect of eptifibatide for acute coronary syndromes
T2 - Rapid versus late administration - Therapeutic yield on platelets (The EARLY platelet substudy)
AU - Gurbel, Paul A.
AU - Galbut, Brian
AU - Bliden, Kevin P.
AU - Bahr, Raymond D.
AU - Roe, Matthew T.
AU - Serebruany, Victor L.
AU - Gibler, W. Brian
AU - Christenson, Robert H.
AU - Ohman, E. Magnus
PY - 2002/12
Y1 - 2002/12
N2 - 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.
AB - 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.
KW - Antiplatelet therapy
KW - Eptifibatide
KW - Platelet receptors
KW - Platelets
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U2 - 10.1023/A:1025048726396
DO - 10.1023/A:1025048726396
M3 - Article
C2 - 12913401
AN - SCOPUS:0042915886
VL - 14
SP - 213
EP - 219
JO - Journal of Thrombosis and Thrombolysis
JF - Journal of Thrombosis and Thrombolysis
SN - 0929-5305
IS - 3
ER -