Effect of clopidogrel with and without eptifibatide on tumor necrosis factor-alpha and C-reactive protein release after elective stenting: results from the CLEAR PLATELETS 1b study.

OBJECTIVES: This study was performed to compare the effects of antiplatelet regimens on early inflammation and cardiac marker release after elective stenting. BACKGROUND: Few data exist regarding the comparative effects of specific antiplatelet regimens on early inflammation marker release after stenting. METHODS: In a 2 x 2 factorial randomized investigation, patients undergoing stenting were treated with either clopidogrel alone (300 mg or 600 mg; n = 60) or clopidogrel with eptifibatide (n = 60). Platelet aggregation (5 and 20 muM adenosine diphosphate [ADP]), ADP-stimulated expression of active glycoprotein (GP) IIb/IIIa, and platelet-bound P-selectin, tumor necrosis factor (TNF)-alpha, C-reactive protein (CRP), and cardiac markers were measured. RESULTS: Compared with a strategy of clopidogrel alone, clopidogrel + eptifibatide reduced the release of cardiac markers. A marked reduction in platelet aggregation and active GP IIb/IIIa expression (p < or = 0.001) with clopidogrel + eptifibatide was associated with a decrease in CRP and TNF-alpha release (p < or = 0.001). CONCLUSIONS: A strategy of clopidogrel with GP IIb/IIIa blockade resulted in superior inhibition of inflammation and cardiac marker release, which was accompanied by superior platelet inhibition immediately after percutaneous coronary intervention compared with a strategy of clopidogrel alone. The mechanistic and clinical implications of attenuated periprocedural inflammation and myocardial necrosis with a strategy of GP IIb/IIIa inhibition warrant further investigation.     

Debate of adjunctive pharmacology for percutaneous coronary intervention: anticoagulation and clopidogrel are not (always) enough

Substantial controversy exists regarding the optimal pharmacologic cocktail for percutaneous coronary intervention (PCI). The most common approach typically includes aspirin, clopidogrel, unfractionated heparin (or enoxaparin), and (variably) a glycoprotein (GP) IIb/IIIa inhibitor. Some substitute bivalirudin with "bail-out" GP IIb/IIIa blockade for heparin and planned GP IIb/IIIa integrin blockade, an approach that necessarily includes aspirin and clopidogrel (for their antiplatelet effects). These shifts in adjunctive treatment paradigms should be examined in the context of available data from clinical studies. Several studies have demonstrated the phenomenon of clopidogrel resistance to be fairly prevalent; even in clopidogrel-responsive patients, steady state is achieved only 4-6 hours after a 600-mg loading dose. It would thus be anticipated that clopidogrel-resistant patients would benefit from GP IIb/IIIa blockade, particularly during the period immediately after intervention. Neither REPLACE-2 nor the recent ACUITY trial demonstrated an efficacy advantage for bivalirudin as a substitute for heparin plus GP IIb/IIIa blockade; instead, any advantage appears to be limited to reducing the propensity for bleeding. As bleeding is directly correlated with the degree of anticoagulation and is further augmented by GP IIb/IIIa blockade, an alternative to the bivalirudin strategy is to simply reduce the amount of heparin anticoagulation during PCI. Finally, the benefit-to-risk ratio of aggressive adjunctive antiplatelet/antithrombotic therapy might be further improved via risk stratification, with patients at higher risk for periprocedural events receiving intensive therapy and lower-risk patients being managed with less intensive regimens focused on minimizing the risk of bleeding.     

Planned versus provisional use of glycoprotein IIb/IIIa inhibitors in smokers undergoing percutaneous coronary intervention

Postmortem and angiographic studies have demonstrated that thrombosis is the primary cause of coronary artery occlusion in smokers. Further, smokers have high levels of fibrinogen, increased platelet aggregation, and more platelet-dependent thrombin generation than do nonsmokers, suggesting that glycoprotein (GP) IIb/IIIa inhibitor use during percutaneous coronary intervention (PCI) may be especially useful among smokers. We evaluated a subpopulation of active smokers in the REPLACE-2 trial to assess the effect of treating smokers with bivalirudin and provisional GP IIb/IIIa blockade compared with heparin and planned GP IIb/IIIa blockade. The REPLACE-2 trial enrolled 1,558 smokers and 4,305 nonsmokers. Smokers who were treated with bivalirudin had an absolute 3.2% increase in the composite end point of death and myocardial infarction at 48 hours compared with smokers who were treated with heparin and GP IIb/IIIa inhibitors (7.7% vs 4.5%, p=0.008, interaction p=0.016). This difference was ameliorated when GP IIb/IIIa inhibitors were used consistently in a previous trial that compared bivalirudin with heparin during PCI (4.6% vs 6.7%, p=0.322). In conclusion, these results suggest that smokers may derive particular benefit with GP IIb/IIIa inhibitors for decreasing myocardial infarction and death after PCI. These findings require further validation from other large, randomized trials.     

Lack of clopidogrel pretreatment effect on the relative efficacy of bivalirudin with provisional glycoprotein IIb/IIIa blockade compared to heparin with routine glycoprotein IIb/IIIa blockade: a REPLACE-2 substudy

OBJECTIVES: The purpose of this study was to assess if clopidogrel pretreatment affects the relative efficacy of bivalirudin versus heparin with glycoprotein (GP) IIb/IIIa blockade for percutaneous coronary interventions (PCI). BACKGROUND: Although thienopyridine pretreatment may improve clinical outcomes with PCI, it is unknown if bivalirudin's efficacy compared with heparin is dependent upon such pretreatment. METHODS: The Randomized Evaluation in Percutaneous coronary intervention Linking Angiomax to reduced Clinical Events (REPLACE-2) trial was a double-blind, triple-dummy, randomized-controlled trial comparing heparin plus routine GP IIb/IIIa blockade (heparin group) with bivalirudin plus provisional GP IIb/IIIa blockade (bivalirudin group) during PCI. The primary end point was a composite of death, myocardial infarction (MI), urgent revascularization at 30 days, and major in-hospital bleeding. The secondary end point was a 30-day composite of death, MI, and urgent revascularization. Clopidogrel pretreatment was encouraged (300 mg loading, 75 mg/day). RESULTS: Of 6,010 patients enrolled, 5,893 received clopidogrel, with 85.8% in the bivalirudin and 84.6% in the heparin group receiving clopidogrel pretreatment. Bivalirudin (provisional GP IIb/IIIa blockade 7.2%) was noninferior to the heparin group for both primary and secondary end points. Clopidogrel pretreatment did not affect the relative efficacy of bivalirudin versus heparin with GP IIb/IIIa blockade, irrespective of pretreatment duration. Pretreatment was associated with significantly lower primary end point with bivalirudin (8.7% pretreatment vs. 12.9% no pretreatment, p = 0.007), and nonsignificantly with heparin (9.7% vs. 11.7%, respectively, p = 0.20). Multivariable models showed a trend toward lower primary and secondary end points with clopidogrel pretreatment. CONCLUSIONS: Clopidogrel pretreatment at the doses and time administered in this trial did not influence the relative efficacy of bivalirudin versus heparin plus GP IIb/IIIa blockade for PCI. However, pretreatment was associated with a trend towards lower clinical events after PCI.     

Relation of local platelet glycoprotein IIb/IIIa independent activation during coronary angioplasty in acute myocardial infarction to recovery of left ventricular function

We assessed glycoprotein (GP) IIb/IIIa independent platelet activation in coronary sinus and peripheral blood from patients who underwent angioplasty for acute myocardial infarction and stable angina. Despite complete blockade of the activated GP IIb/IIIa receptor with abciximab in patients with acute myocardial infarction, unsuppressed local GP IIb/IIIa independent activation was associated with a lack of recovery of left ventricular function.     

Bivalirudin in PCI: an overview of the REPLACE-2 trial

The Randomized Evaluation in PCI Linking Angiomax to Reduced Clinical Events (REPLACE)-2 trial is one of the largest acute randomized controlled trials evaluating the efficacy of two anticoagulant strategies during contemporary urgent or elective percutaneous coronary intervention (PCI). The direct thrombin inhibitor, bivalirudin, with provisional use of glycoprotein IIb/IIIa (GP IIb/IIIa) inhibitor was compared to low-dose unfractionated heparin (UFH) plus planned GP IIb/IIIa inhibitor. At 30-day follow-up, the primary quadruple composite endpoint (death, myocardial infarction (MI), urgent repeat revascularization, or in-hospital major bleeding) occurred in 9.2% of patients in the bivalirudin group versus 10.0% of patients in the UFH plus GP IIb/IIIa inhibitor group. The secondary triple composite endpoint (death, MI, urgent repeat revascularization) occurred in 7.6% of patients in the bivalirudin group compared with 7.1% of patients in the UFH plus GP IIb/IIIa inhibitor group. Both endpoints met formal statistical criteria for noninferiority to UFH plus GP IIb/IIIa inhibitor. By imputed comparison from historic GP IIb/IIIa trials between bivalirudin versus UFH alone, REPLACE-2 demonstrated that bivalirudin was superior to UFH alone with respect to the quadruple and triple composite endpoints. Furthermore, bivalirudin plus provisional GP IIb/IIIa blockade was associated with a significant reduction in in-hospital bleeding (2.4% vs. 4.1%; p < 0.001). At 6 months' follow-up, there was no significant difference in rates of death, MI, or revascularization between the two groups. Furthermore, there was no evidence that the early, nonsignificant 0.5% excess non-Q-wave MI in the bivalirudin group translated into later mortality. There was a trend toward decreased mortality at 6 months in the bivalirudin arm (0.95% vs. 1.35%; p = 0.148). The relative efficacy of bivalirudin versus UFH plus GP IIb/IIIa inhibitor was similar in several high-risk subgroups, including patients with diabetes mellitus or prior MI, women, the elderly (age > 65 years), and patients undergoing PCI of bypass grafts. Bivalirudin represents an exciting alternative to UFH plus GP IIb/IIIa inhibitor in patients undergoing urgent and elective PCI with similar suppression of ischemic events, fewer bleeding complications, and the potential for greater cost savings and ease of administration.     

Chemical structures and mode of action of intravenous glycoprotein IIb/IIIa receptor blockers: A review

Glycoprotein (GP) IIb/IIIa receptor antagonists compose a subcategory of antiplatelet medications that reduce thrombus formation through the blockade of key binding sites needed to stabilize the forming platelet aggregate. The GP IIb/IIIa receptors have been identified as a therapeutic target in reducing the occurrence of platelet-dependent thrombus formation. One advantage of GP IIb/IIIa receptor antagonists is that because GP IIb/IIIa is platelet-specific, inhibition of this receptor does not affect platelet adhesion. This may contribute to hemostasis without leading to ischemic damage. The platelet-specific pharmacological activity of GP IIb/IIIa receptor antagonists has allowed for its broad use in clinical settings. Based on clinical trials, GP IIb/IIIa receptor antagonists have been extensively studied and used in patients with acute coronary syndrome or during percutaneous coronary interventions. The goal of the present article is to provide a detailed review of the chemical structures and mode of action of currently used Food and Drug Administration-approved GP IIb/IIIa receptor antagonists in the United States.     

Platelet activation as a potential mechanism of GP IIb/IIIa inhibitor-induced thrombocytopenia.

The blockade of the platelet integrin glycoprotein (GP) IIb/IIIa has proved to be an effective antiplatelet therapy. Profound thrombocytopenia has repeatedly been described as an adverse effect in patients treated with GP IIb/IIIa inhibitors, but its mechanism has not been elucidated yet. With use of flow cytometry, the activation status of platelets was monitored in 26 patients presenting with acute myocardial infarction who were treated with the GP IIb/IIIa inhibitor abciximab alone or in combination with the fibrinolytic agent reteplase. Fibrinogen and PAC-1 (a GP IIb/IIIa activation-specific monoclonal antibody) binding, as well as P-selectin expression on unstimulated platelets were constant in 25 patients throughout a follow-up of 7 days. In 1 patient (D.F.), the percentage of platelet-binding fibrinogen increased from 2.2% to 17.8%, for PAC-1 from 2.8% to 13.2%, and for P-selectin expression from 10.2% to 58.3% 10 minutes after the start of treatment. Furthermore, D.F. had a decrease in single platelet count in ethylenediaminetetraacetic acid-, citrate-, and heparin-anticoagulated and native blood. Blood films revealed platelet aggregates. In vitro testing of D.F.'s blood 2 and 4 weeks after initial admission demonstrated a reinduction of fibrinogen and PAC-1 binding to platelets, an increase of P-selectin expression, and formation of platelet aggregates following exposition of platelets to abciximab in vitro. In summary, this report describes the induction of platelet activation by a GP IIb/IIIa inhibitor in vivo and reinduction in vitro in direct association with thrombocytopenia. Platelet activation by GP IIb/IIIa inhibitors may be one potential mechanism for GP IIb/IIIa inhibitor-induced thrombocytopenia.     

Impact of platelet glycoprotein IIb/IIIa Inhibition on the paclitaxel-eluting stent in patients with stable or unstable angina pectoris or provocable myocardial ischemia (a TAXUS IV substudy)

Whether the benefits that glycoprotein IIb/IIIa inhibitors confer in patients who undergo bare metal stent implantation extend to drug-eluting stents is unknown. We performed a prespecified subgroup analysis of the TAXUS IV study population to examine the effect of procedural glycoprotein IIb/IIIa inhibition during paclitaxel-eluting stent implantation on periprocedural creatine kinase-MB (CK-MB) levels. Glycoprotein (GP) IIb/IIIa inhibitors were administered to 57.7% of patients who had been randomized to receive the TAXUS stent and to 56.7% of those who had been randomized to receive the control stent. Among patients who received the TAXUS stent, the rate of CK-MB increases of >3 times the normal level was 2.6-fold higher in those who received a GP IIb/IIIa inhibitor than in those who did not (11.4% vs 4.4%, p = 0.0015). Composite rates of major adverse cardiac events and target vessel failure were also higher at 1 month in the GP IIb/IIIa group. By multivariate analysis, use of GP IIb/IIIa inhibitors during stenting with the TAXUS stent was an independent predictor of CK-MB increases >3 times the normal level. Further studies are warranted.     

Evolution in the practice of primary angioplasty: effect of adjunctive coronary stenting and glycoprotein IIb/IIIa inhibitors on long-term outcomes.

Primary angioplasty strategies have evolved dramatically, including increasing adjunctive use of stents and glycoprotein (GP) IIb/IIIa inhibitors. The purpose of this study was to examine the specific effects of these adjunctive therapies on long-term outcomes after primary angioplasty. From 1996 to 1998, 257 unselected, consecutive patients underwent primary PTCI at our institution. In-hospital mortality was 5.4% (2.9% for patients without cardiogenic shock). The remaining 243 patients were followed for 2.0 +/- 0.7 years. Adjunctive stenting was associated with increased late mortality (8.7% vs. 2.3%, P = 0.02). GP IIb/IIIa inhibitors were associated with reduced late mortality among patients receiving stents (6.9% vs. 21.4%, P = 0.07), but not in those patients treated with balloon angioplasty alone (2.9% vs. 0%, P > 0.20). Coronary stenting remained a significant predictor of late mortality (hazard ratio 5.6, 95% CI 1.5-21.2) after adjustment for other established risk factors. In this unselected series, adjunctive coronary stenting was associated with higher late mortality among hospital discharge survivors. Concomitant GP IIb/IIIa inhibitors partially corrected for this increase. These results are limited by the small sample size and retrospective design of this study. Additional long-term studies are required to test these findings and evaluate for possible mechanisms.     

Use of platelet glycoprotein IIb/IIIa inhibitors in saphenous vein graft percutaneous coronary intervention and clinical outcomes

Platelet glycoprotein (GP) IIb/IIIa inhibitors are widely used in percutaneous coronary intervention (PCI). Previous studies have suggested that they do not offer benefit in saphenous vein graft PCI. Nonetheless, their use remains widespread during vein graft angioplasty. We retrospectively analyzed 1,537 patients who underwent saphenous vein graft PCI. Patients who received a GP IIb/IIIa inhibitor (n = 941) were compared with those who did not receive any GP IIb/IIIa inhibitor (n = 596). The primary end point was myonecrosis after PCI (creatine kinase-MB level >3 times the upper reference limit). The incidence of myonecrosis after PCI was similar between the group that received GP IIb/IIIa and the group that did not (odds ratio for GP IIb/IIIa use 1.39, 95% confidence interval 0.97 to 2.00, p = 0.07). Propensity-adjusted analysis demonstrated no significant difference in myonecrosis after PCI, in-hospital mortality, Q-wave myocardial infarction, or bleeding (blood transfusion, retroperitoneal bleed, or hematoma) between the 2 groups. In an analysis restricted to patients who were treated with an emboli protection device, GP IIb/IIIa use was not associated with decreased myonecrosis after PCI (this was also the case for patients who were not treated with an emboli protection device). Unadjusted survival (mean follow-up 5.5 +/- 0.1 years) was similar between the group that received GP IIb/IIIa and the group that did not (log-rank test, p = 0.89). There was no difference in survival after adjusting for the propensity to receive a GP IIb/IIIa inhibitor (adjusted odds ratio for GP IIb/IIIa use 0.92, 95% confidence interval 0.69 to 1.23, p = 0.59). In conclusion, adjunctive use of platelet GP IIb/IIIa inhibitors in saphenous vein graft PCI does not appear to be associated with less myonecrosis or improved survival.     

Pharmacodynamic profile of short-term readministration of abciximab in healthy subjects

Objective The purpose of the study was to establish a rebolus regimen for abciximab that restores pharmacologic glycoprotein (GP) IIb/IIIa receptor blockade within a short time frame (up to 48 hours) after completion of an initial treatment. Methods and Results The study was a single-center, nonrandomized, open-label dose escalation trial in healthy volunteers (n = 30). Each subject received a 0.25 mg/kg bolus and a 0.125 μg/kg per minute infusion of abciximab, followed by incremental bolus doses of the agent at 15-minute intervals up to 48 hours (10 per group) after completion of the infusion, (maximal cumulative rebolus dose of 0.25 mg/kg). Pharmacodynamic measurements (GP IIb/IIIa receptor blockade, turbidimetric and whole blood platelet aggregation with use of a rapid platelet function assay [RPFA]) were obtained at periodic intervals during and after administration of the abciximab bolus and infusion. At the time of the first rebolus, pharmacodynamic measurements were attained immediately before administration of each rebolus and 15 minutes after the last rebolus dose. In subjects who received reboluses 12 hours after infusion, a cumulative dose of 0.05 mg/kg restored >80% blockade of GP IIb/IIIa receptors and >80% inhibition of turbidimetric (5 and 20 μmol/L adenosine diphosphate) and RPFA aggregation in 10 of 10 subjects. At 24 hours after treatment, a cumulative abciximab bolus dose of 0.1 mg/kg restored >80% blockade of all 4 pharmacodynamic measurements in 10 of 10 subjects. At 48 hours after treatment, a cumulative bolus dose of 0.15 mg/kg restored >80% blockade of all 4 pharmacodynamic measurements in 10 of 10 subjects. Conclusions A fraction of the bolus of abciximab restored pharmacologic (>80%) GP IIb/IIIa receptor blockade when readministered at various postinfusion time points. These observations suggest that in the setting where acute readministration of abciximab is required less than a full bolus dose of the agent is warranted. (Am Heart J 2002;143:87-94.)     

Therapeutic dissolution of an intracoronary thrombus by prolonged intravenous platelet glycoprotein IIb/IIIa antagonism

This case report describes the therapeutic dissolution of an intracoronary thrombus in a patient with ectatic coronary arteries post-myocardial infarction by prolonged intravenous glycoprotein (GP) IIb/IIIa antagonist administration. The report emphasizes the potential thrombotic complications in patients with ectatic coronary arteries and the beneficial use of GP IIb/IIIa receptor antagonists as direct thrombolytic agents even in partially organized thrombus formation. In addition to the well-documented effects of GP IIb/IIIa blockade in the scenario of percutaneous interventions, unstable angina, and non-Q wave infarction, the use of this new class of drugs in acute myocardial infarction seems to be promising and might also be considered in the setting of persistent thrombotic material within the coronary vasculature.     

Rheolytic thrombectomy and platelet glycoprotein IIb/IIIa blockade for stent thrombosis.

Conventional transcatheter-based strategies result in good procedural success but poor clinical outcome in the treatment of intracoronary stent thrombosis. A combined approach of mechanical thrombus burden reduction using AngioJet rheolytic thrombectomy with adjunctive glycoprotein (GP) IIb/IIIa antagonists has not been studied. Between July 1998 and August 2000, 15 patients (17 procedures) underwent AngioJet thrombectomy for stent thrombosis at the Beth Israel Deaconess Medical Center. Patients were followed clinically through 6 months following the AngioJet procedure. All patients presented with signs of acute myocardial infarction at a median of 6 days following the original stenting procedure. Most vessels (88%) were occluded at presentation. A GP IIb/IIIa inhibitor was administered during 16 of the 17 procedures. Rheolytic thrombectomy resulted in complete removal of filling defects in all reviewed cases and led to significant improvement in lumen diameter and TIMI flow with reduction in the thrombotic lesion length (all P values < 0.05). Angiographic success (< 30% residual stenosis, TIMI 3 flow) was attained in all but one procedure. No patient required emergent coronary bypass grafting, repeat coronary angioplasty, or died in-hospital. At 6 months, there were no deaths and repeat revascularization was performed in four patients (29%). A combined approach of rheolytic thrombectomy with adjunctive GP IIb/IIIa blockade was highly effective in resolving stent thrombosis and was associated with favorable acute and long-term outcomes.     

Direct thrombin inhibition appears to be a safe and effective anticoagulant for percutaneous bypass graft interventions.

BACKGROUND: Percutaneous coronary interventions (PCI) of coronary artery bypass grafts (CABG) are associated with worse outcomes compared with those of native coronary PCI. Little is known concerning the use of direct thrombin inhibition during CABG intervention. The objective of this report is to examine the safety and efficacy of bivalirudin with GPIIb/IIIa blockade inhibition in patients undergoing CABG PCI. GP IIb/IIIa use was provisional in REPLACE-2 and planned in REPLACE-1. METHODS AND RESULTS: A post hoc analysis of patients undergoing CABG PCI in the REPLACE-1 and -2 trials was performed. In REPLACE-1, patients were randomized to either heparin or bivalirudin, with GP IIb/IIIa inhibitor use at the operator's discretion. In REPLACE-2, patients were randomized to heparin plus GP IIb/IIIa inhibition versus bivalirudin with provisional GP IIb/IIIa blockade. In both studies, randomized treatment groups were well matched. In unadjusted and logistic regression analysis, there were no significant differences in the combined endpoint of death, myocardial infarction, urgent revascularization, or major bleeding when patients were treated with either heparin or bivalirudin. Individual safety and efficacy endpoints were also similar. Minor bleeding was significantly reduced in patients treated with bivalirudin (14.8% vs. 22.7%, P = 0.037). Follow-up data available from the REPLACE-2 trial at 12 months found similar efficacy between groups with a trend towards decreased 12 month mortality in the bivalirudin vs. heparin groups (4.2% vs. 7.8%, P = 0.16). CONCLUSION: CABG PCI using bivalirudin with provisional GPIIb/IIIa inhibition appears to provide similar safety and efficacy to heparin with GPIIb/IIIa inhibition.     

Anti-thrombotic, anti-platelet and fibrinolytic therapy: current management of acute myocardial infarction

Significant advances in the treatment of patients with acute myocardial infarction (MI) have been obtained in recent times. In particular, thrombolytic therapy has been shown to preserve ventricular function and improve survival in patients with acute MI. Therapies now include third-generation thrombolytic agents, percutaneous transluminal coronary angioplasty (PTCA) and intracoronary stenting, and new anti-thrombotic therapies including anti-platelet treatment with glycoprotein (GP) IIb/IIIa inhibition and direct anti-thrombin agents. This review will focus on the use of GP IIb/IIIa antagonists and thrombin inhibitors as adjunctive therapies to thrombolytic treatment of patients with acute MI.     

Synthetic inhibitors of platelet glycoprotein IIb/IIIa in clinical development

Activation of the platelet glycoprotein (GP IIb/IIIa) receptor on the platelet surface is the final pathway of platelet aggregation, regardless of the initiating stimulus. Inhibitors of GP IIb/IIIa receptors include monoclonal antibodies (abciximab) against this receptor and peptidic and nonpeptidic synthetic specific receptor blockers. Abciximab exchanges between and binds to platelets for as long as 2 weeks, whereas synthetic GP IIb/IIIa inhibitors inhibit ex vivo platelet aggregation for only a few hours after the end of infusion, but some have the advantage of also being orally active. In the secondary prevention of atherothrombosis, large-scale trials were successfully conducted with aspirin, dipyridamole, ticlopidine, and clopidogrel. In the first large-scale trials with GP IIb/IIIa inhibitors, abciximab was investigated. In aggregate, synthetic GP IIb/IIIa inhibitors, combined with aspirin and heparin, were shown to reduce ischemic events in patients with high- and low-risk coronary intervention, stents, unstable angina, and non-Q-wave infarction. With short-term use of synthetic GP IIb/IIIa inhibitors, there is no suppression of clinical evident restenosis 6 months after the end of treatment. With the doses currently used, bleeding occurs more often with the synthetic GP IIb/IIIa inhibitors (used for 3 days) than with abciximab (used for 12 hours), but there are no direct comparisons between these drugs.     

Predictors of hospital outcomes after percutaneous coronary intervention in the community

BACKGROUND: It is not well established to what degree advances have been adopted into contemporary percutaneous coronary intervention (PCI) practice in the community and what effect they have on the short-term outcomes of in-hospital mortality and length of stay. METHODS: We analyzed a prospectively-collected, statewide registry that includes consecutive patients undergoing isolated PCI to determine predictors of in-hospital outcomes after the first PCI performed in the community. Multivariable logistic regression analysis was used to determine factors associated with in-hospital mortality after first PCI. RESULTS: Between January 1, 1999 and December 31, 2000 there were a total of 12,920 cases of first PCI performed, 4535 (35.1%) of which were for acute myocardial infarction (MI). Stents and glycoprotein (GP) IIb/IIIa inhibitors were used in 89.6% and 70.0%, respectively, of all cases. In-hospital mortality was 1.8%. Length of hospital stay was 1 (1, 3) days [median (interquartile range)] in the absence of acute MI, and 3 (2, 4) days after acute MI. After acute MI, peri-procedure GP IIb/IIIa inhibitor use [adjusted OR 0.41 (95% CI 0.26, 0.63)] and stenting [adjusted OR 0.61 (95% CI 0.37, 0.996)] were the only factors positively associated with freedom from hospital death. CONCLUSIONS: Intracoronary stenting and use of GP IIb/IIIa inhibitors have been well integrated into community practice. The observed in-hospital mortality rate is slightly higher than published in other series, but likely reflects the significant proportion of acute MI cases being treated aggressively with PCI as the primary therapy.     

Thrombolysis and adjunctive therapies in acute myocardial infarction

Thrombolysis and percutaneous transluminal angioplasty represent the cornerstone of the pharmacologic treatment of and the interventional approach to patients with myocardial infarction (MI). They are very effective. However, they are hampered by some critical limitations. Therefore, alternatives to standard thrombolytic therapy have been developed. Platelet glycoprotein (GP) IIb/IIIa blockade is under investigation and seems very attractive. This review will focus on the use of GP IIb/IIIa antagonists and thrombin inhibitors as adjunctive therapies to the thrombolytic treatment of patients with acute MI.     

Uncoupling in the expression of platelet GP IIb/IIIa in human endothelial cells and K562 cells: absence of immunologic crossreactivity between platelet GP IIb and the vitronectin receptor alpha chain [see comments]

Platelet glycoproteins (GP) IIb and IIIa exist as noncovalently associated Ca++-dependent heterodimer complexes within the platelet membrane and express the major platelet alloantigens Leka (Baka) and PIA1 (Zwa), which are genetic markers of GP IIb and GP IIIa, respectively. Since heterodimers immunologically related to platelet GP IIb/IIIa have been identified in a number of nucleated cell types, we tested anti-Leka and anti-PIA1 antiserum, polyclonal anti-platelet GP IIb/IIIa IgG, as well as a panel of 28 monoclonal anti-GP IIb, GP IIIa, or complex dependent anti-GP IIb/IIIa antibodies on endothelial cells, peripheral blood mononuclear cells, and the erythroleukemic cells HEL and K562 in order to determine whether nucleated cell GP IIb/IIIa related proteins and platelet GP IIb/IIIa are immunologically related. Using immunofluorescence, immunoblotting, and immunoprecipitation experiments, evidence is presented that (1) the alloantigen Leka is not expressed in endothelial cells of an individual whose platelets are of the Leka/PIA1 phenotype, whereas the PIA1 alloantigen is readily detectable in these cells, (2) that in contrast to HEL cells, which express platelet GP IIb/IIIa and are of the Leka/PIA1 phenotype, platelet GP IIb is immunologically undetectable in 12-O-tetradecanoyl- phorbol-13-acetate (TPA)-treated K562 cells despite the presence of platelet GP IIIa, and (3) that peripheral blood mononuclear cells do not express platelet GP IIb or GP IIIa on their cell surface.