1. Administration of abciximab to patients receiving tirofiban or eptifibatide: effect on platelet function
E I Lev, J I Osende, M F Richard, J A Robbins, J A Delfin, O Rodriguez, S K Sharma, T Jayasundera, J J Badimon, J D Marmur J Am Coll Cardiol. 2001 Mar 1;37(3):847-55. doi: 10.1016/s0735-1097(00)01181-5.
Objectives: The goal of this study was to evaluate platelet function and to preliminarily assess the clinical safety of sequential treatment with tirofiban or eptifibatide followed by abciximab in patients undergoing percutaneous coronary intervention (PCI). Background: An increasing number of acute coronary syndrome (ACS) patients are treated early with tirofiban or eptifibatide. Some later require PCI and may benefit from switching to abciximab, for which long-term benefits have been reported. Methods: Fifty ACS patients planned for PCI were enrolled. Twenty-five patients received tirofiban followed by abciximab. Ten patients received eptifibatide followed by abciximab. Fifteen patients received only abciximab. All patients had blood samples drawn six times during the therapeutic course. Platelet function was evaluated by ADP- and TRAP-induced aggregation, flow cytometry analysis of fibrinogen binding and the cone and plate(let) analyzer, which tests shear rate-dependent platelet activation. Results: Administered after tirofiban, abciximab caused a significant further decline in platelet function, as evidenced by all methods. Administered after eptifibatide, abciximab caused a significant further reduction in platelet function, as assessed by the cone and plate(let) analyzer and fibrinogen binding methods. The platelet inhibition achieved by the combination therapy was always greater than or equal to that achieved by abciximab alone. There were no major bleeding or severe thrombocytopenia episodes. Three of the 35 combination therapy patients and one of the 15 who received abciximab alone had minor bleeding. Conclusions: This is the first in vivo study of combination intravenous platelet glycoprotein IIb/IIIa inhibitor therapy. Administration of abciximab immediately after tirofiban or eptifibatide therapy effectively inhibits platelet function and appears to be safe.
2. Long-term mortality after bolus-only administration of abciximab, eptifibatide, or tirofiban during percutaneous coronary intervention
Jonathan D Marmur, Shyam Poludasu, Jason Lazar, Erdal Cavusoglu Catheter Cardiovasc Interv. 2009 Feb 1;73(2):214-21. doi: 10.1002/ccd.21773.
Objective: To evaluate the long-term mortality after bolus-only administration of abciximab, eptifibatide, and tirofiban during percutaneous coronary intervention (PCI). Background: Studies on platelet glycoprotein IIb/IIIa receptor inhibitors (GPI) administered as bolus-only during PCI suggest that this strategy may be similar in efficacy, safer, and more cost-effective compared to a bolus plus infusion of GPI. Methods: We evaluated 864 patients (abciximab = 274, eptifibatide = 361, and tirofiban = 229) who underwent PCI with a bolus-only regimen during January 2003 to August 2005. Results: After a median follow up of four (interquartile range, 3-4.5) years, there were a total of 95 (11%) deaths. The survival rate was 83% in the abciximab group, 91% in the eptifibatide group, and 93% in the tirofiban group (P = 0.003 by log-rank test). After adjustment for baseline clinical and procedural characteristics using a Cox proportional hazards model, the abciximab group had a significantly higher mortality compared to the eptifibatide group (P = 0.003; Hazard ratio (HR) for eptifibatide compared to abciximab was 0.49 (95% confidence intervals [CI]: 0.30-0.78). The long-term mortality was not significantly different in the tirofiban group compared to the abciximab group (P = 0.33) or the eptifibatide group (P = 0.20), perhaps because of shorter follow-up period and fewer patients in the tirofiban group. Conclusion: When given as bolus-only during PCI, eptifibatide may improve long-term survival compared to abciximab.
3. Antiplatelet effects of abciximab, tirofiban and eptifibatide in patients undergoing coronary stenting
F J Neumann, W Hochholzer, G Pogatsa-Murray, A Schömig, M Gawaz J Am Coll Cardiol. 2001 Apr;37(5):1323-8. doi: 10.1016/s0735-1097(01)01165-2.
Objectives: We sought to investigate whether abciximab, tirofiban and eptifibatide achieve comparable antiplatelet effects with coronary stenting. Background: The glycoprotein (GP) IIb/IIIa antagonists abciximab, tirofiban and eptifibatide differ in chemical structure, binding site and pharmacokinetics. Methods: Sixty patients undergoing coronary stenting were randomly assigned to abciximab (bolus 0.25 mg/kg body weight, infusion 10 microg per min for 12 h), tirofiban (bolus 10 microg/kg, infusion 0.15 microg/kg per min for 72 h) or eptifibatide (bolus 180 microg/kg, infusion 2 microg/kg per min for 72 h). We took serial blood samples to analyze platelet function by using flow cytometry, turbidimetric aggregometry and the rapid platelet-function assay (RPFA). Results: As assessed by RPFA, platelet aggregation after 2 h of infusion was reduced to 5.9 +/- 7.8% (mean +/- SD) of baseline by abciximab, to 5.0 +/- 5.4% by tirofiban and to 7.8 +/- 7.1% by eptifibatide (p = 0.42). Turbidimetric aggregometry with adenosine diphosphate stimulation yielded similar results, whereas percent inhibition of platelet aggregation after thrombin receptor stimulation was 45.8 +/- 16.8% with abciximab, 51.3 +/- 17.6% with tirofiban and 52.9 +/- 14.8% with eptifibatide (p = 0.37). Tirofiban and eptifibatide maintained their level of platelet inhibition during infusion. Flow cytometry revealed that the reduction in the monocyte-platelet interaction by abciximab, tirofiban and eptifibatide was not significantly different (20.0 +/- 21.9%, 23.8 +/- 18.2% and 21.0 +/- 19.8%, respectively; p = 0.87). Conclusions: Abciximab, tirofiban and eptifibatide, at currently recommended doses, achieved similar levels of inhibition of platelet aggregation and a similar reduction in the platelet-monocyte interaction.
