Antiplatelet effects of abciximab, tirofiban and eptifibatide in patients undergoing coronary stenting

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.     

Update on Glycoprotein IIb/IIIa Blockade in Endovascular Interventions

Platelet aggregation plays a central role in the ischemic complications of percutaneous coronary interventions (PCI) and the acute coronary syndromes (ACS). Although aspirin and heparin have been effective at decreasing adverse events in these settings, the perceived need for more potent inhibition of platelet aggregation has led to targeting of the platelet surface membrane glycoprotein IIb/IIIa (GP IIb/IIIa) receptor. Several agents have been developed; four: abciximab, tirofiban, eptifibatide, and lamifiban have been tested in clinical trials. Overall, the positive findings of these studies have supported the hypothesis that enhanced platelet blockade leads to improved clinical outcomes in the settings of PCI and ACS. In this article, an overview of the various GP IIb/IIIa receptor inhibitors is presented. The clinical trials of these agents as adjunctive therapy for patients undergoing PCI and in treatment of acute myocardial infarction are reviewed. Practical considerations relating to clinical efficacy, drug safety, and economic issues are discussed.     

A comparative study of light transmission aggregometry and automated bedside platelet function assays in patients undergoing percutaneous coronary intervention and receiving abciximab, eptifibatide, or tirofiban.

Platelet inhibition is central to the efficacy of glycoprotein (GP) IIb-IIIa antagonist therapy, but is not routinely measured during percutaneous coronary intervention (PCI). Data directly comparing the antiplatelet effects of these agents are also limited. Therefore, we compared ex vivo platelet function by standard light transmission aggregometry (LTA) and two automated bedside platelet function assays in 36 patients undergoing PCI with GP IIb-IIIa inhibitors. At baseline and 10 min following clinically recommended bolus and infusion of abciximab (0.25 mg/kg, 0.125 microg/kg/min), eptifibatide (180 microg/kg, 2 microg/kg/min), or tirofiban (10 microg/kg, 0.1 microg/kg/min), we measured 20 microM ADP- and 1.9 mg/mL collagen-induced platelet aggregation using LTA. Platelet function was also assessed using the bedside Accumetrics Ultegra-Rapid Platelet Function Assay (RPFA) and the Xylum Clot Signature Analyzer (CSA). The degree of platelet inhibition, as assessed by LTA, varied significantly between the clinically recommended doses of these GP IIb-IIIa antagonists. RPFA measurements agreed closely with LTA for abciximab, but tended to overestimate the degree of platelet inhibition for small molecules. CSA demonstrated profoundly inhibited shear-induced platelet function, but lacked sensitivity to discriminate between agents. These findings may have implications for the results of trials comparing the efficacy of these agents in patients undergoing PCI.     

Platelet glycoprotein IIb/IIIa inhibitor use during percutaneous coronary intervention: IIb or Not IIb,what is the question?

Over the past decade, numerous placebo-controlled randomized clinical trials have documented robust clinical benefits of intravenous platelet glycoprotein (GP) IIb/IIIa inhibitors in patients undergoing percutaneous coronary intervention (PCI). This evidence has led to U.S. Food and Drug Administration approval and indication for use of two GP IIb/IIIa inhibitors at the time of PCI, namely, the chimeric monoclonal antibody fragment abciximab (ReoPro, Centocor, Inc. and Eli Lilly & Company) and the cyclic heptapeptide small molecule eptifibatide (Integrilin, COR Therapeutics and Key Pharmaceuticals). Currently, another small molecule GP IIb/IIIa inhibitor, tirofiban (Aggrastat, Merck & Company), which (similar to eptifibatide) is approved for the medical therapy of patients with non-ST segment elevation acute coronary syndromes (ACS), has not received indication for use in the PCI setting. Although the clinical benefits of both abciximab and eptifibatide administered at the time of PCI have been proven in randomized clinical trials, only abciximab has demonstrated a late survival advantage in patients following PCI. Evidence in support of the presence, magnitude and possible mechanisms for abciximab survival advantage is herein reviewed.     

GP IIb/IIIa inhibitors during primary percutaneous coronary intervention for STEMI: New trial and registry data

Primary percutaneous coronary intervention (PCI) with adjunctive glycoprotein (GP) IIb/IIIa receptor inhibitor therapy administered in the cardiac catheterization laboratory is the optimal reperfusion strategy for patients with ST-elevation myocardial infarction. Most available data regarding these agents are from trials comparing abciximab to placebo alone. Noninferiority trials comparing small-molecule GP IIb/IIIa receptor inhibitors, such as tirofiban and eptifibatide with abciximab, have used markers for myocardial reperfusion as primary end points but are underpowered to detect significant differences in hard clinical outcomes. Such a trial would need to enroll a very large number of patients and thus make it practically impossible to perform. Registry data reveal that most patients undergoing primary PCI are treated with small-molecule GP IIb/IIIa receptor inhibitors in clinical practice, and no observed difference is observed in safety and efficacy when compared with patients treated with abciximab therapy.     

Meta-analysis of effectiveness and safety of abciximab versus eptifibatide or tirofiban in percutaneous coronary intervention

Three platelet glycoprotein (GP) IIb/IIIa receptor antagonists have been evaluated in patients undergoing percutaneous coronary intervention (PCI). One of these agents, abciximab, is structurally and pharmacologically quite different from the other 2, eptifibatide and tirofiban. We conducted a meta-analysis to determine whether different antagonist types achieved different clinical outcomes, possibly related to their structural differences. Odds ratios (OR) were calculated and a random effects model was used to combine the outcomes of 14,644 patients enrolled in 8 prospective, randomized, placebo-controlled clinical trials assessing treatment with a GP IIb/IIIa inhibitor to prevent ischemic complications of PCI. Neither abciximab (OR 0.69; 95% confidence interval [CI] 0.4 to 1.9) nor eptifibatide or tirofiban treatment (OR 0.74; 95% CI 0.4 to 1.28) resulted in reductions in mortality. Only the abciximab-treated patients had reductions in myocardial infarction (4.3% vs 8.5%, OR 0.49; 95% CI 0.40 to 0.59). There was no effect of eptifibatide or tirofiban on myocardial infarction (OR 0.85; 95% CI 0.69 to 1.04). Urgent revascularization was reduced in both abciximab-treated (2.7% vs 6.2%, OR 0.42; 95% CI 0.34 to 0.53) and eptifibatide- and tirofiban-treated (4.2% vs 5.5%, OR 0.76; 95% CI 0.60 to 0.96) groups. Only abciximab-treated patients had increased major bleeding (5.8% vs 3.8%; OR 1.53; 95% CI 1.24 to 1.90). There was no effect of eptifibatide or tirofiban on major bleeding (5.0% vs 4.3%; OR 1.19; 95% CI 0.94 to 1.52). Thus, significant differences exist between clinical outcomes achieved by abciximab and those achieved by eptifibatide or tirofiban following PCl procedures.     

Differential Effects of Citrate Versus PPACK Anticoagulation on Measured Platelet Inhibition by Abciximab, Eptifibatide and Tirofiban

Background: High levels of glycoprotein (GP) IIb/IIIa receptor inhibition are required to prevent arterial thrombosis following percutaneous coronary intervention. Ex-vivo turbidometric platelet aggregation in citrate anticoagulated blood samples has been the primary method previously utilized to derive dose regimens for administering platelet GP IIb/IIIa inhibitors. Enhanced GP IIb/IIIa binding and inhibition of platelet aggregation for eptifibatide secondary to citrate induced reduction of ionized plasma calcium concentrations has been reported. Methods/Results: We evaluated the differential effects of citrate versus PPACK anticoagulation on turbidometric platelet inhibition in normal volunteers by eptifibatide, tirofiban or abciximab. The decrease in ionized calcium afforded by citrate was associated with enhanced in vitro platelet inhibition for all three GP IIb/IIIa inhibitors, including abciximab. The magnitude of citrate effect was greatest for eptifibatide. Both tirofiban and abciximab have similar citrate calcium chelation associated enhancement of measured platelet inhibition.Conclusion: Accurate assessment and comparison of platelet inhibition by GP IIb/IIIa inhibitors may require avoidance of calcium chelating anticoagulants.     

Thrombocytopenia after treatment with platelet glycoprotein IIb/IIIa inhibitors

Abciximab, eptifibatide, and tirofiban are the three drugs approved by the US Food and Drug Administration designed to block platelet aggregation by binding glycoprotein IIb/IIIa. Results from large therapeutic trials demonstrate that all three agents induce thrombocytopenia in approximately 1% to 5% of cardiac patients. Thrombocytopenia is typically rapid in onset and antibody mediated. In vitro evidence suggests abciximab-induced thrombocytopenia is associated with antibodies directed to murine sequences within the chimeric anti-IIb/IIIa molecule. In addition, abciximab, eptifibatide, and tirofiban also function as mixed agonist-antagonists in vivo, inducing neoepitopes within the glycoprotein IIb/IIIa receptor that may react with pre-existing or induced antibodies. Screening for the development of these antibodies may reduce the incidence of thrombocytopenia associated with these agents, but it may limit their chronic usage.     

Administration of abciximab to patients receiving tirofiban or eptifibatide: effect on platelet function.

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.     

Optimal duration of eptifibatide infusion in percutaneous coronary intervention (an ESPRIT substudy)

Although randomized trials have clearly demonstrated the clinical efficacy with regimens of platelet glycoprotein IIb/IIIa antagonists that result in >80% inhibition of baseline platelet aggregation in percutaneous coronary intervention (PCI), there are no data available concerning the optimal duration of infusion of these agents. In an era when the length of hospitalization has a major impact on health care costs, the determination of the optimal duration of the infusion of these drugs after PCI is of great relevance. The investigators therefore sought to determine the optimal length of the infusion of eptifibatide after PCI by analyzing the outcomes of patients enrolled in the Enhanced Suppression of the Platelet IIb/IIIa Receptor With Integrilin Therapy trial who were randomized to treatment with eptifibatide.     

Long‐term mortality after bolus‐only administration of abciximab,eptifibatide, or tirofiban during percutaneous coronary intervention

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. © 2009 Wiley‐Liss, Inc.     

Achieved platelet aggregation inhibition after different antiplatelet regimens during percutaneous coronary intervention for ST-segment elevation myocardial infarction

OBJECTIVES: To evaluate the extent of platelet aggregation inhibition in patients with ST-segment elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI), treated with different antiplatelet agents and dosages. BACKGROUND: The extent of platelet aggregation inhibition is an independent predictor of major cardiac events after elective PCI. In STEMI patients undergoing PCI, routine dose of antiplatelet agents may be associated with less effective platelet aggregation inhibition. METHODS: Patients were treated with clopidogrel before angiography and randomized to abciximab, tirofiban, high-dose tirofiban, or no glycoprotein (GP) IIb/IIIa inhibitor; GP IIb/IIIa inhibitor bolus, followed by maintenance infusion, was administered after angiography, but before PCI. Platelet aggregation inhibition was assessed before angiography, immediately after PCI, and 1 and 6 h afterwards. RESULTS: The total study population consisted of 112 patients. Platelet aggregation inhibition was variable for individuals and suboptimal for all agents, particularly in the periprocedural period. Only with high-dose tirofiban, mean periprocedural platelet aggregation inhibition exceeded 80%. Angiographic parameters after PCI were not different between the groups. No relationship was found between the level of platelet aggregation and parameters of PCI success (Thrombolysis In Myocardial Infarction frame count and myocardial blush grade), after combining the data from all four groups studied. CONCLUSIONS: Platelet aggregation inhibition in STEMI patients undergoing PCI, treated with antiplatelet agents, is variable and suboptimal for all agents and dosages studied. Only with high-dose tirofiban, mean periprocedural platelet aggregation inhibition exceeded 80%. However, no relationship of platelet aggregation inhibition and angiographic outcome was found in this patient cohort.     

Optimizing glycoprotein IIb/IIIa inhibition: lessons from recent randomized controlled trials

Recent randomized clinical trials with intravenous glycoprotein IIb/IIIa inhibition have provided unanticipated results, thereby questioning their role as empirical medical management for acute coronary syndromes. The lack of benefit with abciximab observed in Global Utilization of Strategies to Open Occluded Coronary Arteries IV is somewhat inconsistent with the benefits seen with this agent in coronary intervention, and the benefits of an early invasive approach incorporating tirofiban seen within Treat Angina with Aggrastat and determine Cost of Therapy with an Invasive or Conservative Strategy Thrombolysis in Myocardial Infraction 18. Additionally, a direct 'head-to-head' comparative study of abciximab and tirofiban within the setting of percutaneous coronary intervention demonstrates clinically relevant superiority with abciximab with respect to 30-day outcomes. in the setting of coronary instability and mechanical plaque disruption is more complex than initially perceived. Hence, although an abundance of evidence details the efficacy of these agents, their optimal clinical application remains somewhat challenging in light of these recent data. However, within the context of previous trial experience, the current evidence highlights several key aspects of glycoprotein IIb/IIIa inhibitor therapy that may be associated with improved patient outcomes. In particular, these trials indicate: (i) the importance of selecting high-risk patients in whom substantial clinical benefit is evident, (ii) the incorporation of these agents into an early invasive strategy, thereby matching the timing of vascular injury with maximal platelet inhibition and (iii) optimal dosing to achieve the high levels of platelet inhibition that appear to be required for efficacy with these agents.     

Design and methodology of the ESPRIT trial: evaluating a novel dosing regimen of eptifibatide in percutaneous coronary intervention

BACKGROUND: Clinical trials of the glycoprotein (GP) IIb/IIIa inhibitors have shown that these potent antiplatelet agents are effective in reducing the ischemic complications of percutaneous coronary interventions. However, even though stents are now implanted in >75% of percutaneous interventional procedures, only one study, a trial of the monoclonal antibody abciximab, has formally evaluated adjunctive GP IIb/IIIa inhibition in this setting. METHODS AND RESULTS: Eptifibatide, a nonimmunogenic and rapidly reversible inhibitor of the platelet receptor integrin IIb/IIIa, has also undergone evaluation as an adjunct to coronary intervention. In clinical trials performed heretofore, however, it has appeared to have less relative clinical efficacy than the monoclonal antibody abciximab. Since the early seminal trials, it has been recognized that the doses of eptifibatide previously used achieved only 30% to 50% of maximal platelet GP IIb/IIIa integrin inhibition. This is considerably less than the 80% level of receptor inhibition that has been proposed to prevent coronary thrombus formation in animal models and that has been achieved in clinical trials with abciximab. CONCLUSIONS: The Enhanced Suppression of the Platelet IIb/IIIa Receptor with Integrilin Therapy (ESPRIT) trial was designed to test the safety and efficacy of a high-dose, "180/2.0/180" double-bolus regimen of eptifibatide (a 180-microg/kg bolus followed 10 minutes later by a second 180-microg/kg bolus of eptifibatide combined with a 2.0-microg/kg per minute infusion) as an adjunct to nonacute percutaneous coronary intervention with stent implantation. In this report, we review the rationale, design, and methods of this clinical investigation.     

Safety of glycoprotein IIb/IIIa inhibitors in urgent or emergency coronary artery bypass graft surgery

Approximately 2% to 4% of patients undergo urgent or emergency coronary artery bypass grafting (CABG) for complications of percutaneous coronary intervention (PCI) after treatment with glycoprotein (GP) IIb/IIIa inhibitors. The pharmacokinetic and pharmacodynamic properties of GP IIb/IIIa inhibitors play a large role in determining the safety of their use in the setting of urgent or emergency CABG procedures. Emergency or urgent CABG after treatment with the GP IIb/IIIa inhibitor, abciximab, may be associated with increased risk of hemorrhage and the requirement of platelet transfusions if surgery is performed within 12 h of abciximab discontinuation. Eptifibatide is associated with a similar risk compared with placebo, even when surgery is performed within 2 h of eptifibatide cessation. Limited data for tirofiban show that bleeding is not increased when compared with acetylsalicylic acid or heparin. Eptifibatide and tirofiban appear to have favourable safety profiles compared with abciximab in the setting of emergency or urgent CABG after failed PCI.     

Platelet inhibition with tirofiban early during percutaneous coronary intervention: dosing revisited.

Platelet inhibition is central to the efficacy of the intravenous glycoprotein IIb/IIIa receptor inhibitors. Differences in the degree of platelet inhibition achieved with these agents may account for the disparity in clinical efficacy noted in recently completed clinical trials. The purpose of this study was to evaluate ex vivo platelet inhibition with tirofiban in patients admitted with acute coronary syndrome and who were referred for percutaneous coronary interventions. Twenty-five patients were studied. Ten patients received tirofiban 10 microg/kg bolus and 0.15 microg/kg infusion for 16 hr. Platelet inhibition was determined at 5, 15, 30, 45, 60, and 120 min after tirofiban, by light transmission aggregometry (LTA), rapid platelet function assay (RPFA), and platelet works (PW). The average platelet inhibition using RPFA with PPACK, was 87% at 5 min, then decreased to a nadir of 72% at 30 min and recovered back to > 80% at 60 min and onward. Similar trends were noted with RPFA-citrate, PW, and LTA. Ca-chelating anticoagulants (EDTA and citrate) overestimated platelet inhibition at all time points. Dose adjustment was done by increasing the bolus (15 microg/kg) in five patients, increasing the maintenance dose (0.2 microg/kg/min) in five patients, and increasing both the bolus and the maintenance dose in another five patients. Platelet inhibition tested by all the above methods was consistently over 90% when both the bolus and maintenance doses were increased. No increased incidence of major bleeding was noted at this adjusted dose. The current dosing of tirofiban may be inadequate to achieve appropriate platelet inhibition during PCI in patients admitted with acute coronary syndrome and receiving tirofiban immediately before the procedure in the cardiac catheterization laboratory. Dose adjustment may be needed to maximize platelet inhibition early during PCI.     

Determination of platelet aggregation inhibition during percutaneous coronary intervention with the platelet function analyzer PFA-100

Background A simple device to rapidly evaluate platelet function may aid in optimizing glycoprotein IIb/IIIa inhibition during percutaneous coronary intervention (PCI). We prospectively studied platelet function in 250 patients receiving abciximab or eptifibatide during PCI. Methods and Results The platelet function analyzer PFA-100 (Dade-Behring, Deerfield, Ill) measures platelet function by determining the time to occlusion of an aperture in a biochemically active membrane as whole blood flows under high shear conditions. Platelet aggregation causes aperture occlusion, and results are reported as a closure time (CT). All patients received either abciximab or eptifibatide, along with aspirin and heparin; patients undergoing stent implantation received aspirin and a thienopyridine postprocedure. The CT was measured at baseline and 10 minutes, 4 hours, 12 hours (abciximab-only), and 24 hours after the bolus. Profound inhibition was exhibited in most patients shortly after the platelet inhibitor bolus and during the course of therapy. We observed recovery of platelet function 12 hours after discontinuation of abciximab, with a high degree of interpatient variability, and ongoing profound platelet inhibition 4 to 6 hours after the discontinuation of eptifibatide. Among patients treated with abciximab, patients who were obese recovered from platelet inhibition sooner than patients who were not obese, whereas patients who were elderly had delayed recovery compared with patients who were not elderly. Failure to achieve maximal platelet inhibition (nonclosure) at 10 minutes indicated a possible association with adverse clinical events at the 6-month follow-up examination (60% vs 20%). Conclusions PFA-100 is a rapid simple assay used as a means of assessing inhibition of platelet aggregation during PCI performed with glycoprotein IIb/IIIa inhibition. Failure to achieve nonclosure early after the initiation of abciximab therapy warrants further investigation because there may be an association with adverse cardiac events at 6-month follow-up. (Am Heart J 2002;144:151-8.)     

Comparative pharmacodynamic evaluation of eptifibatide and tirofiban HCl in patients undergoing percutaneous coronary intervention (the TAM1 Study)

We performed a comparative analysis of platelet aggregation inhibition achieved with the glycoprotein IIb/IIIa inhibitors eptifibatide and tirofiban HCl in patients who underwent percutaneous coronary intervention and used light transmission aggregometric assays with D-phenylalanyl-L-prolyl-L-arginine chloromethyl ketone as an anticoagulant and 20 micromol of adenosine diphosphate as an agonist. Taking into account the differences in clinical efficacy of these 2 drugs in large trials investigating percutaneous coronary intervention, we hypothesized that the variable clinical effects might be related to variability in the magnitude and consistency of platelet aggregation inhibition achieved with dosing regimens of these glycoprotein IIb/IIIa inhibitors.     

Short-Term Comparative Outcomes Associated with the Use of GP IIb/IIIa Antagonists in Patients Undergoing Coronary Intervention

Background:Platelet glycoprotein (GP) IIb/IIIa antagonists reduce the occurrence of death, myocardial infarction (MI) and urgent revascularization among patients undergoing percutaneous coronary intervention (PCI). Despite a similar mechanism of platelet inhibition, the three currently approved agents vary widely in cost. Purpose: The purpose of this prospectively designed, retrospective analysis was to determine clinical outcomes for patients receiving abciximab, tirofiban or eptifibatide as adjunctive therapy during PCI at a single center. We hypothesized that there would be no difference in outcomes during hospitalization following PCI in patients receiving tirofiban or eptifibatide compared with those patients who received abciximab. Outcomes examined included in-hospital mortality, hemorrhagic procedural complications, need for recatheterization, peak creatine kinase following intervention and length of hospital stay (LOS). Results: Two hundred and sixty seven consecutive patients in whom GP IIb/IIIa antagonist therapy was initiated in the catheterization laboratory for PCI were analyzed. Abciximab-treated patients were more likely to be undergoing primary (p<0.001) and rescue (p=0.022) PCI and to have received fibrinolytic therapy (p=0.013) when compared to patients receiving tirofiban or eptifibatide. There were no significant differences between abciximab- and non abciximab-treated patients in either the primary PCI or non primary PCI groups in any of the studied endpoints. In patients undergoing primary PCI, abciximab-treated patients when compared with non abciximab-treated patients exhibited a trend toward an increase in hospital LOS (7.8±7.0 d vs 6.2±3.9, p=0.19) and in the frequency of hemmorhagic complications (22.1% vs 5.3%, p=0.11). In patients not receiving fibrinolytic therapy, abciximab-treated patients experienced a trend toward increased hemmorhagic complications following PCI when compared to non abciximab-treated patients (10.2% vs 6.0%, p=0.28). Complications distant from the vascular access site comprised 62.5% of hemmorhagic complications in the abciximab-treated group, but only 20% of the complications in the non-abciximab treated population (p<0.001). These data suggest no differences in acute outcomes between groups of patients receiving abciximab or other approved GP IIb/IIIa antagonists highlighting a potential significant cost saving. These data will require interpretation following the publication of comparative trials.     

Platelet glycoprotein IIb/IIIa receptor blockade in coronary artery disease

New strategies for profound inhibition of platelet activity at the injured coronary plaque focus on blockade of the platelet surface membrane glycoprotein IIb/IIIa receptor, which binds circulating fibrinogen or von Willebrand factor and crosslinks platelets as the final common pathway to platelet aggregation. Intravenous agents directed against this receptor include the chimeric monoclonal antibody fragment abciximab, the peptide inhibitor eptifibatide and nonpeptide mimetics tirofiban and lamifiban. Over 33,000 patients have been evaluated in 11 large-scale, placebo-controlled trials of these agents. During percutaneous coronary intervention, an absolute reduction of 1.5% to 6.5% in the 30-day risk of death, myocardial infarction or repeat urgent revascularization has been observed, with some variability in treatment effect among the agents tested (abciximab, eptifibatide and tirofiban). Treatment effect is achieved early with every modality of revascularization and is maintained over the long-term (up to three years). Increased bleeding risk may be minimized by reduction and weight-adjustment of concomitant heparin dosing. In the acute coronary syndromes without ST segment elevation, absolute 1.5% to 3.2% reductions in 30-day rates of death or myocardial (re-) infarction have been achieved with two to four day courses of eptifibatide or tirofiban. Clinical benefit accrues during the period of drug infusion and is durable. Treatment effect may be enhanced among patients undergoing early coronary revascularization, with evidence of stabilization before intervention and suppression of postprocedural ischemic events. Thus, blockade of the platelet glycoprotein IIb/IIIa receptor reduces ischemic complications when used as an adjunct to percutaneous coronary intervention or the management of acute ischemic syndromes.