Abciximab, ticlopidine, and concomitant abciximab-ticlopidine therapy: ex vivo platelet aggregation inhibition profiles in patients undergoing percutaneous coronary interventions.
BACKGROUND
We examined the ex vivo platelet aggregation profiles of patients who underwent percutaneous coronary intervention and received either abciximab, ticlopidine, or both agents.


METHODS
The trial was a prospective, nonrandomized, single-center, open-label study of 42 patients undergoing percutaneous coronary intervention who received the following regimens: group 1, abciximab (0.25 mg/kg bolus and 12-hour, 0.125 microg/kg per minute infusion); group 2, ticlopidine (250 mg twice daily for 14 consecutive days, initiated 12 to 18 hours before intervention); group 3, abciximab plus ticlopidine initiated 12 to 18 hours before procedure; and group 4, abciximab plus ticlopidine initiated 72 to 96 hours before procedure. Platelet aggregation measurements to adenosine diphosphate (ADP) and a thrombin receptor activating peptide (TRAP, 8 micromol/L) were obtained before ticlopidine treatment, after initiation of ticlopidine, and immediately before abciximab treatment and intervention, then at several time periods after onset of abciximab treatment. Platelet surface abciximab levels were monitored by flow cytometry.


RESULTS
Neither ticlopidine regimen resulted in appreciable platelet inhibition before intervention and before administration of abciximab. In the ticlopidine-only arm, suppression of platelet aggregation to the weakest stimuli (5 micromol/L ADP; 23% +/- 7.5%) was detected within 24 hours after intervention, with maximal inhibition to both 5 and 20 micromol/L ADP observed 7 days after intervention (48% +/- 7.9% and 18% +/- 8.7%, respectively). In contrast, ticlopidine marginally suppressed TRAP-mediated platelet activation at times when maximal effects on ADP-mediated platelet aggregation were evident. Neither ticlopidine regimen appreciably enhanced platelet inhibition during or shortly after cessation of abciximab treatment. For all 3 abciximab treatment arms, profound inhibition of ADP-induced (>80%) and TRAP-induced (>65%) platelet aggregation was observed 2 hours after treatment. In the abciximab-only arm, platelet aggregation responses gradually recovered, with the rate of response directly proportional to the strength of stimuli. However, in the ticlopidine plus abciximab arms, recovery of platelet aggregation at later times (7 and 14 days) reached a plateau and reflected the extent of inhibition observed in ticlopidine-treated patients. No difference in the clearance of surface-bound abciximab from circulating platelets was observed between the abciximab and abciximab plus ticlopidine arms.


CONCLUSIONS
Concomitant abciximab plus ticlopidine treatment yields a platelet inhibition profile that is a composite of the effects of the 2 agents. In the early stages of treatment, inhibition of ex vivo platelet aggregation was mediated primarily by abciximab; effects were more moderate and were predominately mediated by ticlopidine.
Kleiman
N S
NS
Baylor College of Medicine and the Methodist Hospital, Houston, TX, USA.
Grazeiadei
N
N
Maresh
K
K
Taylor
R J
RJ
Frederick
B
B
Lance
E T
ET
Effron
M B
MB
Jordan
R E
RE
Mascelli
M A
MA
D000077284:Abciximab; D000368:Aged; D015906:Angioplasty, Balloon, Coronary / Q000009:adverse effects*; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D003328:Coronary Thrombosis / Q000503:physiopathology / Q000517:prevention & control; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage*; D010979:Platelet Function Tests; D011183:Postoperative Complications / Q000517:prevention & control; D011446:Prospective Studies; D013988:Ticlopidine / Q000008:administration & dosage*
D000911:Antibodies, Monoclonal; D007140:Immunoglobulin Fab Fragments; D010975:Platelet Aggregation Inhibitors; D013988:Ticlopidine; D000077284:Abciximab