Comparative pharmacodynamic evaluation of eptifibatide and abciximab in patients with non-ST-segment elevation acute coronary syndromes: the TAM2 study.
BACKGROUND
The importance of the relationship between clinical outcome and degree of platelet aggregation inhibition (PAI) achieved with the dosing regimens of GPIIb-IIIa inhibitors used in large trials in patients with non-ST segment elevation (NSTE) acute coronary syndromes (ACS) is increasingly appreciated. In the PURSUIT trial, eptifibatide treatment that consistently provided >80% PAI was associated with clinical benefit at 30 days and 6 months. The GUSTO IV ACS trial, however, did not show any effect of abciximab on 30-day outcomes. This difference might be due to variability of antiplatelet effects of these drugs. As previous studies found, a 12 hr abciximab infusion had <80% PAI, particularly at 6 and 12 hr. These studies did not evaluate PAI with a longer, 24-hour infusion as used in GUSTO IV ACS.


METHODS
We conducted a prospective study in 40 patients with NSTE ACS prior to catheterization or coronary intervention at 3 centers using the PURSUIT dose of eptifibatide (180/2.0) [DOSAGE ERROR CORRECTED] and the GUSTO IV dose of abciximab (0.25, 0.125). Blood samples were collected at baseline, and during the infusion at 10 min, 1 hr, 6 hr, 8 hr, 12 hr, 18 hr, and 24 hr. Measurements of ex vivo light transmission aggregometry (LTA) were performed using PPACK anticoagulant and 20 microM ADP agonist. Receptor Occupancy (RO) was also determined in a subset of patients.


RESULTS
Eptifibatide achieves higher PAI during the entire infusion period than abciximab (p<0.01). At 10 min, average PAI with eptifibatide and abciximab was 88% and 80%, respectively, 95% and 79% at 6 hr, and 97% and 79% at 24 hr. There was also more variability in individual patient response to abciximab. Although average RO for eptifibatide was similar to that of abciximab at 10 min, 67% versus 69%, respectively, average RO was higher in the eptifibatide cohort at all subsequent timepoints. By 24 hr, average RO for eptifibatide was 86%, whereas abciximab averaged 67%.


CONCLUSIONS
These data support the hypothesis that differences in clinical outcomes of large GPIIb-IIIa trials in patients with NSTE ACS may be related to the consistency and potency of antiplatelet effects of the dosing regimens used.
Saucedo
Jorge F
JF
University of Arkansas for Medical Sciences and Central Arkansas Veterans Health Care System, Little Rock, Arkansas, USA.
Lui
Henry K
HK
Garza
Luis
L
Guerra
G Jose
GJ
Jacoski
Mary V
MV
Jennings
Lisa K
LK
D000077284:Abciximab; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000494:pharmacology* / Q000627:therapeutic use; D003327:Coronary Disease / Q000097:blood* / Q000188:drug therapy; D000077542:Eptifibatide; D005260:Female; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D010455:Peptides / Q000494:pharmacology* / Q000627:therapeutic use; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors; D011446:Prospective Studies; D013577:Syndrome
D000911:Antibodies, Monoclonal; D007140:Immunoglobulin Fab Fragments; D010455:Peptides; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D000077542:Eptifibatide; D000077284:Abciximab