Ticlopidine enhances the platelet inhibitory capacity of abciximab in vitro

Ticlopidine and abciximab are two antiplatelet agents that are frequently administered during percutaneous coronary interventions. Although they have different mechanisms of action and pharmacological profiles, the two agents are often concomitantly used in complicated stent placements. The purpose of the study was to evaluate the effect of ticlopidine therapy on the capacity of abciximab to inhibit platelet aggregation, in vitro. Blood samples from 13 ticlopidine-treated stent placement patients and 8 patients undergoing PTCA who did not receive ticlopidine were obtained prior to, 12-36 hours and 7-10 days after initiating ticlopidine treatment. For each patient, the minimal ADP and the thrombin receptor activating peptide (TRAP) concentrations that elicited maximal platelet aggregation responses at baseline were used to measure the extent of platelet aggregation and the abciximab concentration that gave a 50% decrease in aggregation (IC(50)) for both agonists at the three time points. The ticlopidine group baseline and 12-36 hour mean ADP aggregation responses were equivalent, but decreased by 34% (P = 0.009) at 7-10 days. The control group ADP and TRAP, as well as the ticlopidine group TRAP aggregation responses, were equivalent at all time points. The ticlopidine group baseline and 12-36 hour abciximab IC(50) values for ADP were comparable (1.58 +/- 1.1 ng/mL vs. 1.23 +/- 0.5 ng/mL; P = 0.266), but decreased to 1.00 +/- 0.6 ng/mL (36%; P = 0.004) at 7-10 days. In contrast, the abciximab IC(50) for TRAP increased from 1.48 +/- 1.0 ng/mL to 1.85 +/- 1.1 ng/mL (25%; P = 0.033) at 12-36 hours, but returned to baseline at 7-10 days (1.40 +/- 0.8; P = 0.975). The control group IC(50) abciximab values for ADP and TRAP were comparable throughout the monitoring period. The results demonstrate that ticlopidine elicits subtle potentiation of the platelet-inhibitory capacity of abciximab to the agonist ADP, but not TRAP, at 1 week after initiation of treatment.