Dalteparin in combination with abciximab during percutaneous coronary intervention.

BACKGROUND: Despite proved efficacy for either dalteparin or platelet glycoprotein IIb/IIIa blockade in improving clinical outcomes of patients with non-ST-segment elevation acute coronary syndromes, algorithms guiding concomitant therapy with these agents have not been devised. The purpose of this study was to assess anticoagulant effect and clinical safety for several dose regimens of dalteparin administered in combination with abciximab during percutaneous coronary intervention (PCI). METHODS AND RESULTS: Patients undergoing PCI with standard dose abciximab received dalteparin as follows: 120 IU/kg subcutaneously (SQ) to a maximum of 10,000 U if < or =8 hours before PCI (n = 3); for PCI 8-12 hours after the SQ dose, an additional 40 IU/kg intravenously (IV) was administered (n = 1); for PCI >12 hours after SQ dalteparin or with no prior dalteparin therapy, random allocation to 40 (n = 27) or 60 (n = 28) IU/kg IV during PCI was performed. Those patients who received 60 IU/kg of dalteparin IV had a lower incidence of procedural thrombosis (0% vs 11.1%, P <.01), more consistent antithrombotic effect (anti-factor Xa activity) and a similar incidence of major bleeding (3.7% vs 2.6%) compared with patients who received 40 IU/kg of intravenous dalteparin. CONCLUSIONS: Dalteparin 60 IU/kg IV appears to be safe and effective when administered in conjunction with abciximab for percutaneous coronary intervention.

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. STUDY DESIGN AND 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.

Effects of abciximab, ticlopidine, and combined Abciximab/Ticlopidine therapy on platelet and leukocyte function in patients undergoing coronary angioplasty.

BACKGROUND: Abciximab and ticlopidine reduce adverse cardiovascular events after percutaneous transluminal coronary angioplasty (PTCA). The goal of the current study was to determine if combined abciximab/ticlopidine therapy inhibits arterial thrombosis more effectively than either treatment alone. The effect of each therapy on platelet-leukocyte interactions was also investigated. METHODS AND RESULTS: Whole blood samples from 14 patients undergoing PTCA who received abciximab therapy, ticlopidine therapy, or both treatments were evaluated using dynamic experimental systems. Mural thrombus formation under arterial shear conditions (1500 s(-1)) was determined in a parallel plate flow chamber. Shear-induced platelet aggregation was evaluated using a cone-and-plate viscometer at a shear rate of 3000 s(-1). Of the 3 treatments, combined abciximab/ticlopidine therapy produced the most consistent reduction in shear-induced platelet aggregation and the most prolonged inhibition of mural thrombosis. Three days after PTCA, abciximab/ticlopidine treatment decreased mural thrombus formation to approximately 50% of baseline values. Abciximab treatment alone inhibited mural thrombosis for only 1 day after PTCA, whereas ticlopidine treatment alone had no significant effect. Two hours after PTCA, abciximab therapy significantly decreased the number of circulating platelet-neutrophil aggregates but significantly enhanced P-selectin-mediated leukocyte adhesion on the collagen/von Willebrand factor-platelet surface. CONCLUSIONS: Combined therapy with abciximab and ticlopidine has a prolonged inhibitory effect on mural thrombosis formation relative to either treatment alone. Further, we demonstrated an unexpected effect of abciximab in enhancing P-selectin-mediated leukocyte adhesion.

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.