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PubMed2002

Bivalirudin with planned or provisional abciximab versus low-dose heparin and abciximab during percutaneous coronary revascularization: results of the Comparison of Abciximab Complications with Hirulog for Ischemic Events Trial (CACHET).

BACKGROUND: The direct thrombin inhibitor bivalirudin has previously been associated with better efficacy and lower hemorrhage risk than heparin during balloon angioplasty. This agent has not yet been tested with stenting or in combination with platelet glycoprotein IIb/IIIa antagonists. METHODS AND RESULTS: In a pilot trial, 268 patients who underwent coronary intervention were randomized in 3 sequential phases to treatment with bivalirudin (with or without abciximab) or the control regimen of low-dose weight-adjusted heparin with abciximab. Patients in the bivalirudin arms received bivalirudin (1.0 mg/kg bolus, infusion of 2.5 mg/kg/h for 4 hours) plus abciximab in phase A, bivalirudin (0.5 mg/kg bolus, infusion of 1.75 mg/kg/h for the procedure duration) plus provisional ("rescue") abciximab in phase B, or bivalirudin (0.75 mg/kg bolus, infusion of 1.75 mg/kg/h for the procedure duration) plus provisional abciximab in phase C. Abciximab was necessitated on a provisional basis in 24% of the patients in the bivalirudin arms of phases B and C. A composite clinical endpoint of death, myocardial infarction, repeat revascularization, or major bleeding by 7 days occurred in 3.3%, 5.9%, 0, and 10.6% of the patients in the bivalirudin phase A, bivalirudin phase B, bivalirudin phase C, and heparin plus planned abciximab arms, respectively (P =.018 for the pooled bivalirudin groups versus the heparin group). CONCLUSION: Bivalirudin with planned or provisional abciximab may be at least as safe and effective as low-dose heparin plus abciximab during percutaneous coronary intervention.

Abciximab↗

PubMed2000

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.

Abciximab↗

PubMed2004

Early administration of reteplase plus abciximab vs abciximab alone in patients with acute myocardial infarction referred for percutaneous coronary intervention: a randomized controlled trial.

CONTEXT: The optimal pharmacological strategy for bridging the delay between admission and performance of percutaneous coronary intervention (PCI) in patients with acute myocardial infarction (MI) is not known. OBJECTIVE: To assess whether early administration of reteplase plus abciximab produces better results compared with abciximab alone in patients with acute MI referred for PCI. DESIGN, SETTING, AND PATIENTS: Open-label, randomized controlled study conducted from May 3, 2001, through June 2, 2003, of 253 patients who were admitted to 13 community hospitals without catheterization facilities (n = 186) and to 5 hospitals with catheterization facilities (n = 67), with the diagnosis of an ST-segment elevation acute MI within 12 hours from onset of symptoms. INTERVENTIONS: Patients received intravenously either the combination of a half-dose reteplase (two 5-U boluses, 30 minutes apart) with a standard dose of abciximab (0.25 mg/kg bolus, 0.125 microg/kg per minute infusion [maximum 10 microg/min for 12 hours]) or the standard dose of abciximab alone; all patients were then transferred for PCI. MAIN OUTCOME MEASURE: Final infarct size according to a single-photon emission computed tomography study with technetium Tc 99m sestamibi performed between 5 and 10 days after randomization in 228 patients (90.1% of entire sample). RESULTS: Of the 253 patients enrolled, 125 were assigned to reteplase plus abciximab and 128 to abciximab alone. The median (interquartile range) of the final infarct size of the left ventricle was 13.0% (3.0%-28.0%) in the reteplase plus abciximab group and 11.5% (3.0%-26.3%) in the abciximab-alone group (P =.81). The mean difference in final infarct size of left ventricle between the reteplase plus abciximab group and the abciximab group was 1.3% (95% confidence interval [CI], -3.1% to 5.7%). Within 6 months after randomization, the composite secondary end point of death, recurrent MI, or stroke occurred in 8 patients (6.4%) in the reteplase plus abciximab group and 6 patients (4.7%) in the abciximab group (relative risk, 1.4; 95% CI, 0.5-3.9; log-rank P =.56). Major bleeding complications were observed in 7 patients (5.6%) in the reteplase plus abciximab group and 2 patients (1.6%) in the abciximab group (P =.16). CONCLUSION: Early administration of reteplase plus abciximab does not lead to a reduction of infarct size compared with abciximab alone in patients with acute MI referred for PCI.

Abciximab↗

PubMed2003

Benefits and risks of abciximab use in primary angioplasty for acute myocardial infarction: the Controlled Abciximab and Device Investigation to Lower Late Angioplasty Complications (CADILLAC) trial.

BACKGROUND: Trials of platelet glycoprotein IIb/IIIa inhibitors as adjuncts to primary percutaneous coronary intervention for acute myocardial infarction (MI) have shown improved early clinical and angiographic outcomes with treatment. However, variations in trial designs, modest sample sizes, and limited long-term follow-up have precluded these studies from being definitive. METHODS AND RESULTS: As a prespecified secondary analysis of the CADILLAC trial, we compared early and late outcomes by abciximab assignment among 2082 patients randomized in an open-label, 2x2 factorial-design trial of primary stenting versus angioplasty and abciximab treatment (n=1052) versus no abciximab treatment (n=1030). Baseline characteristics were balanced between groups. Abciximab treatment was associated with a significant reduction in the composite end point of death, MI, ischemia-driven target-vessel revascularization (TVR), or disabling stroke at 30 days (4.6% versus 7.0%; relative risk, 0.65; 95% CI, 0.46 to 0.93; P=0.01). Subacute thrombosis also was significantly reduced with abciximab treatment. At 12 months, however, rates of the composite end point did not differ significantly (18.4% for controls versus 16.9% for abciximab-treated patients; relative risk, 0.92; 95% CI, 0.76 to 1.10; P=0.29), reflecting a decrease in the relative difference in TVR rates (ie, no effect of abciximab on reducing restenosis). In an angiographic substudy (n=656), myocardial salvage, restenosis, and infarct-artery reocclusion at 7 months were unaffected by abciximab treatment. There was no significant interaction between stenting and abciximab treatment. CONCLUSIONS: Adjunctive abciximab treatment during primary percutaneous coronary intervention significantly enhanced 30-day event-free survival, predominantly by reducing ischemia-driven TVR. Abciximab treatment did not affect the composite end point at 1 year, reflecting a lack of effect on restenosis.

Abciximab↗

PubMed2000

Flow cytometric monitoring of glycoprotein IIb/IIIa blockade and platelet function in patients with acute myocardial infarction receiving reteplase, abciximab, and ticlopidine: continuous platelet inhibition by the combination of abciximab and ticlopidine.

BACKGROUND: Improvement of thrombolysis may be achieved by concomitant strong platelet inhibition. To monitor platelet function in patients with myocardial infarction (n=46) who were treated with the fibrinolytic agent reteplase, the glycoprotein (GP) IIb/IIIa blocker abciximab, and the ADP receptor antagonist ticlopidine, we developed a flow cytometric assay. METHODS AND RESULTS: Binding of abciximab to platelets was directly monitored as the percentage of platelets stained by a goat anti-mouse antibody. Blood drawn 10 minutes and 2 hours after the start of therapy with reteplase and abciximab and during the 12-hour infusion of abciximab demonstrated a maximal blockade of GP IIb/IIIa (10 minutes, 86.2+/-10.3%; 12 hours, 85.8+/-7.1%). Starting at 24 hours, abciximab binding gradually decreased (24 hours, 74.6+/-16.2%; 48 hours, 66.8+/-14.9%; 72 hours, 60.5+/-16.7%; 96 hours, 49.4+/-17.8%; 120 hours, 35.8+/-16. 4%; and 144 hours, 29.9+/-15.3%). Binding of a chicken anti-fibrinogen antibody to platelets, indicating the level of functional blockade of GP IIb/IIIa, was inversely correlated with the binding of abciximab (r=-0.72, P:<0.0001). In blood drawn at 10 minutes, platelet aggregation was maximally inhibited but recovered within 48 hours even if the majority of GP IIb/IIIa receptors were still blocked by abciximab. Reteplase did not influence abciximab binding and did not activate platelets, as measured by P-selectin expression, fibrinogen binding, and platelet aggregation. Platelet inhibition that was achieved during the first 24 hours by abciximab was directly maintained by additional treatment with ticlopidine. CONCLUSIONS: Flow cytometric monitoring of platelet function allows differentiation of the effects of reteplase, abciximab, and ticlopidine. The combination of abciximab and ticlopidine is an attractive therapeutic strategy that provides a fast and continuous platelet inhibition.

Abciximab↗

PubMed2000

Clinical benefit of glycoprotein IIb/IIIa blockade with Abciximab is independent of gender: pooled analysis from EPIC, EPILOG and EPISTENT trials. Evaluation of 7E3 for the Prevention of Ischemic Complications. Evaluation in Percutaneous Transluminal Coronary Angioplasty to Improve Long-Term Outcome with Abciximab GP IIb/IIIa blockade. Evaluation of Platelet IIb/IIIa Inhibitor for Stent.

OBJECTIVES: We sought to determine the efficacy and safety of platelet glycoprotein IIb/IIIa receptor (GP IIb/IIIa) blockade with abciximab in women undergoing percutaneous coronary intervention. BACKGROUND: Although gender differences in response to platelet glycoprotein IIb/IIIa receptor blockade have been described, there have been no large clinical studies to assess these differences. METHODS: Outcomes were determined using meta-analysis technique. RESULTS: In the pooled analysis, the primary end point of death, myocardial infarction (MI) or urgent revascularization within 30 days was reduced from 11.3% to 5.8% (p<0.001) in men and from 12.7% to 6.5% (p<0.001) in women treated with abciximab. At six months, death, MI or urgent revascularization was reduced from 14.1% to 8.3% (p<0.001) in men and 16.0% to 9.9% (p<0.001) in women receiving abciximab. At one year, mortality was reduced from 2.7% to 1.9% (p = 0.06) in men and 4.0% to 2.5% (p = 0.03) in women treated with abciximab. Major bleeding events occurred in 2.9% versus 3.0% (p = 0.96) of women and 2.7% versus 1.3% (p = 0.003) of men treated with placebo versus abciximab, respectively. Minor bleeding events occurred in 4.7% versus 6.7% (p = 0.01) of women and 2.3% versus 2.2% (p = 0.94) of men treated with placebo versus abciximab, respectively. CONCLUSIONS: This pooled analysis demonstrated no gender difference in protection from major adverse outcomes with GP IIb/IIIa inhibition with abciximab. Although women had higher rates of both major and minor bleeding events with abciximab compared with men, major bleeding in women was similar with and without abciximab. There was a small increased risk of minor bleeding with abciximab in women.

Abciximab↗

PubMed1998

Administration of abciximab during percutaneous coronary intervention reduces both ex vivo platelet thrombus formation and fibrin deposition: implications for a potential anticoagulant effect of abciximab.

Abciximab (c7E3 Fab, ReoPro), a platelet glycoprotein (GP) IIb/IIIa inhibitor, decreases acute ischemic complications after percutaneous coronary interventions. Recently, abciximab was shown to decrease thrombin generation in vitro in a static system. To assess whether abciximab can decrease fibrin formation in blood from patients, we quantified both platelet thrombi and fibrin deposition by using an ex vivo flow chamber model. We prospectively studied 18 consecutive patients who underwent percutaneous interventions for unstable coronary syndromes. Blood was perfused directly from the patient through an ex vivo perfusion chamber at a high shear rate, thus mimicking mildly stenosed coronary arteries. Perfusion chamber studies were performed when patients were being treated with heparin plus aspirin before the procedure (baseline) and then repeated after the procedure, when patients were on either aspirin plus heparin alone (group 1, no abciximab, control) or aspirin plus heparin plus abciximab (group 2, abciximab treated). Each patient served as his or her own control. Specimens were stained with combined Masson's trichrome-elastin and antibodies specific for fibrinogen, fibrin, and platelet GP IIIa. Total thrombus area and areas occupied by platelet aggregates and fibrin layers were quantified by planimetry. Group 1 demonstrated no significant change in thrombus area before versus after the procedure; in contrast, treatment with abciximab reduced total thrombus area by 48% in group 2 (after the procedure versus baseline, P=0.01). This decline was due to significant reductions in both platelet aggregates (55%, P=0.005) and fibrin layers (45%, P=0.03). The addition of abciximab to heparin and aspirin in patients undergoing coronary interventions significantly decreases ex vivo thrombus formation on an injured vascular surface. Treatment with abciximab appears to reduce both the platelet and the fibrin thrombus components. This finding supports a potential role for GP IIb/IIIa receptor blockade in decreasing fibrin formation in addition to inhibition of platelet aggregation. Thus, potent inhibitors of GP IIb/IIIa may also act as anticoagulants.

Abciximab↗

PubMed2000

Abciximab and bleeding during coronary surgery: results from the EPILOG and EPISTENT trials. Improve Long-term Outcome with abciximab GP IIb/IIIa blockade. Evaluation of Platelet IIb/IIIa Inhibition in STENTing.

BACKGROUND: Abciximab during percutaneous coronary revascularization reduces ischemic complications, but concern exists regarding increased bleeding risk should emergency coronary surgical procedures be required. METHODS: Outcomes were assessed among 85 patients who required coronary artery bypass grafting operations after coronary intervention in two randomized placebo-controlled trials of abciximab. Comparisons were made between patients in the pooled placebo and abciximab groups. RESULTS: The incidence of coronary surgical procedures was 2.17% and 1.28% among patients randomized to placebo and abciximab, respectively (p = 0.021). Platelet transfusions were administered to 32% and 52% of patients in the placebo and abciximab groups, respectively (p = 0.059). Rates of major blood loss were 79% and 88% in the placebo and abciximab groups, respectively (p = 0.27); transfusions of packed red blood cells or whole blood were administered in 74% and 80% of patients, respectively (p = 0.53). Surgical reexploration for bleeding was required in 3% and 12% of patients, respectively. Death and myocardial infarction tended to occur less frequently among patients who had received abciximab. CONCLUSIONS: Urgent coronary artery bypass grafting operations can be performed without an incremental increase in major hemorrhagic risk among patients on abciximab therapy.

Abciximab↗

PubMed1998

Reduction in complications of angioplasty with abciximab occurs largely independently of baseline lesion morphology. EPIC and EPILOG Investigators. Evaluation of 7E3 for the Prevention of Ischemic Complications. Evaluation of PTCA To Improve Long-term Outcome with abciximab GPIIb/IIIa Receptor Blockade.

OBJECTIVES: We investigated the hypothesis that abciximab might lead to a differential effect among patients with different lesion morphologies; hence, its cost/benefit ratio would be optimized if it were used selectively on the basis of baseline angiographic findings. BACKGROUND: Major complications of coronary angioplasty occur in 4% to 9% of patients. In the Evaluation of 7E3 for the Prevention of Ischemic Complications (EPIC) and Evaluation of PTCA To Improve Long-term Outcome with abciximab GPIIb/IIIa Receptor Blockade (EPILOG) trials, abciximab decreased the ischemic complications after intervention by 35% to 56%. However, the cost of this agent is appreciable, and there remain concerns about the safety of its readministration. METHODS: There were 1,362 patients in EPIC and 2,792 patients in EPILOG randomized to either bolus plus an infusion of abciximab or placebo, administered with aspirin and heparin at the time of the coronary intervention. Data from these studies were combined, and a differential effect of abciximab in relation to baseline lesion morphology on 30-day risk of death, myocardial infarction or urgent intervention was investigated using the Breslow Day test for statistical interaction. RESULTS: Abciximab consistently reduced the relative risk of complications across all lesion morphologies studied, with the possible exception of patients treated with degenerated saphenous vein grafts (risk with placebo 16.3% vs. risk with abciximab 18.6%, Breslow Day test for interaction, p=0.08). However, the absolute reduction of risk was somewhat greater in patients with more complex B2 or C lesions (7.6% and 5.8%, respectively) than in patients with morphologically simpler A or B1 lesions (3.7% and 3.2%, respectively). CONCLUSIONS: The reduction of early adverse ischemic events associated with angioplasty by abciximab occurs largely independent of pretreatment morphology.

Abciximab↗

PubMed2003

Cost-effectiveness of coronary stenting and abciximab for patients with acute myocardial infarction: results from the CADILLAC (Controlled Abciximab and Device Investigation to Lower Late Angioplasty Complications) trial.

BACKGROUND: Both stenting and the glycoprotein IIb/IIIa inhibitor abciximab improve outcomes for patients undergoing primary angioplasty for acute myocardial infarction (AMI). However, the cost-effectiveness of these strategies is unknown. METHODS AND RESULTS: We performed a prospective cost-utility analysis among US participants in the CADILLAC trial. Patients with AMI (n=1703) were randomized to stenting versus balloon angioplasty (PTCA) and abciximab versus no abciximab according to a 2-by-2 factorial design. Total 1-year costs and lifetime incremental cost-effectiveness ratios, measured as cost per quality-adjusted year of life (QALY) gained, were calculated. Compared with PTCA, stenting increased procedural costs by 1148 dollars and initial hospital costs by 1384 dollars (both P<0.001). By 1-year, stenting led to fewer repeat revascularization procedures and reduced follow-up medical care costs by 1215 dollars, such that aggregate costs were similar for the PTCA and stent groups (18 690 dollars versus 18 859 dollars, P=0.75). The cost-effectiveness ratio for stenting versus PTCA was favorable at 11 237 dollars/QALY gained and remained <20 000 dollars/QALY in sensitivity analyses. Compared with standard anticoagulation, abciximab increased initial procedural costs by 1122 dollars (P<0.001). By facilitating accelerated hospital discharge, abciximab reduced length of stay by approximately 0.6 days, offsetting most of the drug costs. These cost offsets were not maintained, however; aggregate 1-year costs for the abciximab group were 1244 dollars greater than for standard therapy (19 389 dollars versus 18 145 dollars , P=0.02). Abciximab was reasonably cost-effective (cost-effectiveness ratio 21 305 dollars/QALY) only if nonsignificant differences in 1-year mortality (3.7% versus 4.3%, P=0.62) were incorporated in the analysis. CONCLUSIONS: Primary stenting is a highly cost-effective treatment for AMI. The cost-effectiveness of abciximab in this setting is uncertain and depends primarily on whether long-term survival is enhanced.

Abciximab↗

PubMed2004

Abciximab-supported infarct artery stent implantation for acute myocardial infarction and long-term survival: a prospective, multicenter, randomized trial comparing infarct artery stenting plus abciximab with stenting alone.

BACKGROUND: The impact on survival of routine use of abciximab as adjunctive treatment to routine infarct artery stenting for acute myocardial infarction is not defined. We sought to determine the effect of abciximab on 1-year survival and other major adverse cardiac events of patients with acute myocardial infarction undergoing routine infarct artery stenting. METHODS AND RESULTS: The Abciximab and Carbostent Evaluation (ACE) Trial is an unblinded, randomized, controlled trial that compared abciximab with placebo in patients undergoing routine infarct artery stent implantation for acute myocardial infarction. At 1 year, the survival rate was 95+/-2% in the abciximab group and 88+/-2% in the stent-alone group (P=0.017). The reinfarction rate was 1% in the abciximab group and 6.0% in the stent-alone group, whereas there were no differences between groups in target vessel revascularization rate (16.5% in the abciximab group, 17.5% in the stent-alone group). CONCLUSIONS: Abciximab as adjunctive treatment to routine infarct artery stenting for acute myocardial infarction resulted in improved 1-year survival and lower reinfarction rates.

Abciximab↗

PubMed2000

Economic assessment of platelet glycoprotein IIb/IIIa receptor blockade with abciximab and low-dose heparin during percutaneous coronary revascularization: results from the EPILOG randomized trial. Evaluation in PTCA to Improve Long-term Outcome with abciximab GP IIb/IIIa blockade.

BACKGROUND: In the EPILOG trial (Evaluation in PTCA to Improve Long-term Outcome with abciximab GP IIb/IIIa blockade), abciximab administered with weight-adjusted heparin diminished the risk of ischemic complications within 30 days by 56% among patients undergoing percutaneous coronary revascularization, without increased bleeding complications. METHODS AND RESULTS: A prospective economic assessment was performed in the 2792 patients enrolled in EPILOG. Patients were randomized to receive placebo with standard-dose weight-adjusted heparin, abciximab with low-dose weight-adjusted heparin, or abciximab with standard-dose weight-adjusted heparin during percutaneous coronary intervention. Hospital billing data for the baseline hospitalization were collected for 2581 patients (92.4% of total) and imputed for the remainder, with physician fees estimated from the Medicare Fee Schedule. For the baseline hospitalization, medical costs (hospitalization and physician fees) averaged $9632 for the placebo arm compared with $8758 (P:=0.005) and $9092 (P:=0.176) for the abciximab with low-dose and standard-dose heparin arms, respectively. Inclusive of average drug cost ($1454 to $1457), the net incremental baseline cost of these 2 abciximab strategies was $583 with low-dose weight-adjusted heparin and $914 with standard-dose weight-adjusted heparin. During 6-month follow-up, average hospital costs were not significantly different in the 3 treatment groups; cumulative net incremental costs were $1236 and $1268 in the abciximab with low-dose and standard-dose heparin groups, respectively. CONCLUSIONS: Treatment with abciximab and low-dose, weight-adjusted heparin during percutaneous coronary revascularization reduces ischemic events and associated costs, thereby offsetting some of the cost of the drug. The suppression of bleeding complications associated with this agent by heparin dose reduction optimizes the economic attractiveness of this treatment strategy.

Abciximab↗

PubMed1999

Sustained suppression of ischemic complications of coronary intervention by platelet GP IIb/IIIa blockade with abciximab: one-year outcome in the EPILOG trial. Evaluation in PTCA to Improve Long-term Outcome with abciximab GP IIb/IIIa blockade.

BACKGROUND: Blockade of the platelet glycoprotein IIb/IIIa receptor with the monoclonal antibody fragment abciximab was shown in a placebo-controlled randomized trial to reduce the incidence of acute ischemic complications within 30 days among a broad spectrum of patients undergoing percutaneous coronary revascularization. The durability of clinical benefit in this setting has not been established. METHODS AND RESULTS: A total of 2792 patients enrolled in the Evaluation in PTCA to Improve Long-term Outcome with abciximab GP IIb/IIIa blockade (EPILOG) trial were followed with maintenance of double-blinding for 1 year. Patients had been assigned at the time of their index coronary interventional procedure to receive placebo with standard-dose, weight-adjusted heparin (100 U/kg initial bolus), abciximab with standard-dose, weight-adjusted heparin, or abciximab with low-dose, weight-adjusted heparin (70 U/kg initial bolus). The primary outcome was the composite of death, myocardial infarction, or urgent repeat revascularization by 30 days; this composite end point and its individual components were also assessed at 6 months and 1 year. Rates of any repeat revascularization (urgent or elective), target vessel revascularization, and a composite of death, myocardial infarction, or any repeat revascularization were also reported. Follow-up at 1 year was 99% complete for survival status and 97% complete for other end points. By 1 year, the incidence of the primary composite end point was 16.1% in the placebo group, 9.6% in the abciximab with low-dose heparin group (P<0.001), and 9.5% in the abciximab with standard-dose heparin group (P<0.001). Each of the components of this composite end point was reduced to a similar extent. Nonurgent or target vessel repeat revascularization rates were not significantly decreased by abciximab therapy. Mortality rates over 1 year increased with increasing levels of periprocedural creatine kinase MB fraction elevation. CONCLUSIONS: Acute reductions in ischemic events after percutaneous coronary intervention by abciximab are sustained over follow-up to at least 1 year. Early periprocedural myocardial infarctions suppressed by this therapy are associated with long-term mortality rates.

Abciximab↗

PubMed2002

Thrombocytopenia after second exposure to abciximab is caused by antibodies that recognize abciximab-coated platelets.

Thrombocytopenia, often severe, occurs in 1% to 2% of patients given the fibrinogen receptor antagonist abciximab, a chimeric Fab fragment containing murine specificity-determining and human framework sequences. The cause of this complication has not yet been defined. Studies of 9 patients who developed profound thrombocytopenia (platelets <10 x 10(9)/L [10 000/microL]) within a few hours of being given abciximab a second time showed that each had a strong immunoglobulin G (IgG) antibody that recognized platelets sensitized with abciximab. Five patients also had IgM antibodies. IgG antibodies reactive with abciximab-coated platelets were also found in 77 (74%) of 104 healthy subjects. However, the patient antibodies could be distinguished from "normal" ones in 2 ways: (1) only the patient antibodies reacted preferentially with platelets sensitized with the intact monoclonal antibody 7E3 from which the murine sequences in abciximab are derived; and (2) the "normal" antibodies could be inhibited by Fab fragments derived from normal human IgG, whereas the patient antibodies were relatively resistant to this treatment. The findings suggest that antibodies from the patients are specific for murine sequences in abciximab and are capable of causing life-threatening thrombocytopenia upon injection of this drug. The antibodies commonly found in healthy subjects are specific for the papain cleavage site of any Fab fragments and, although they react with abciximab-coated platelets, appear not to cause significant thrombocytopenia. It may be possible to identify patients at risk for developing thrombocytopenia if given abciximab by screening for antibodies that recognize 7E3-coated platelets.

Abciximab↗

PubMed2005

Gated SPECT evaluation of outcome after abciximab-supported primary infarct artery stenting for acute myocardial infarction: the scintigraphic data of the abciximab and carbostent evaluation (ACE) randomized trial.

UNLABELLED: We used gated SPECT to evaluate the impact of abciximab on the efficacy of myocardial reperfusion in patients with acute myocardial infarction undergoing infarct-related artery stenting. METHODS: The Abciximab and Carbostent Evaluation (ACE) trial randomized 400 infarct patients to stenting alone or stenting plus abciximab. One-month (99m)Tc-sestamibi gated SPECT was planned in a subgroup of consecutive patients to evaluate infarct size, infarct severity, left ventricular volumes, and ejection fraction. RESULTS: The final study population included 182 patients (99 randomized to abciximab and 83 to stenting alone). Gated SPECT revealed smaller infarcts in the abciximab group than in the stenting-alone group (14.3% +/- 11.7% vs. 18.1% +/- 13%, P < 0.02), and lower infarct severity (minimum-to-maximum count ratio = 0.47 +/- 0.17 vs. 0.41 +/- 0.15, P < 0.02), resulting in a smaller left ventricular end-diastolic volume index (57.8 +/- 20.0 vs. 64.6 +/- 20.8 mL/m(2), P = 0.03) and left ventricular end-systolic volume index (31.7 +/- 17.4 vs. 37.5 +/- 18.6 mL/m(2), P = 0.05) in the abciximab group. One-month left ventricular ejection fraction was significantly higher in patients randomized to abciximab (47.4% +/- 11.3% vs. 43.9% +/- 11.7%, P = 0.05). CONCLUSION: The use of abciximab therapy as an adjunct to infarct-related artery stenting leads to a reduction in infarct size and severity, resulting in smaller 1-mo left ventricular volumes and better left ventricular function. Gated SPECT appears to be an ideal tool for outcome assessment in infarct patients undergoing different treatment strategies.

Abciximab↗

PubMed2006

Abciximab and angiographic restenosis after coronary stent placement. Analysis of the angiographic substudy of ISAR-REACT--a double-blind, placebo-controlled, randomized trial evaluating abciximab in patients undergoing elective percutaneous coronary interventions after pretreatment with a high loading dose of clopidogrel.

BACKGROUND: ISAR-REACT was a trial designed to evaluate whether the glycoprotein IIb/IIIa inhibitor abciximab is beneficial in patients undergoing elective percutaneous coronary intervention (PCI) with stent placement after pretreatment with a 600 mg loading dose of clopidogrel. Objective for the angiographic substudy was to determine the impact of abciximab on angiographic restenosis after coronary stent placement. Previous analyses have suggested a reduction in the incidence of restenosis after the administration of abciximab. METHODS: The angiographic substudy comprises 1885 of 2159 patients enrolled in ISAR-REACT: 994 patients were randomly assigned to abciximab and 941 patients to placebo. All patients were scheduled for a routine angiographic follow-up after 6 months (performed in 80% of eligible patients). End points for the angiographic substudy were the rates of angiographic restenosis (> or = 50% diameter stenosis) and target lesion revascularization. RESULTS: The incidence of angiographic restenosis was 27% in the abciximab group and 29% in the placebo group (relative risk 0.92, 95% CI 0.79-1.06, P = .27). Late angiographic lumen loss was 0.95 +/- 0.68 and 0.99 +/- 0.70 mm, respectively (P = .25). Similar results were obtained in a subgroup analysis focusing on high-risk subsets. The rate of target lesion revascularization procedures was 22% in the abciximab group and 23% in the placebo group (relative risk 0.94, 95% CI 0.79-1.12, P = .52). CONCLUSIONS: In low- to intermediate-risk patients who undergo elective PCI after pretreatment with a high loading dose of clopidogrel >2 hours before PCI, the additional administration of the glycoprotein IIb/IIIa inhibitor abciximab is not associated with a significant reduction in angiographic restenosis.

Abciximab↗

PubMed2002

Thrombin generation and fibrinolytic activities among patients receiving reduced-dose alteplase plus abciximab or undergoing direct angioplasty plus abciximab for acute myocardial infarction.

The purpose of this study was to determine the impact of these 2 reperfusion strategies (reduced-dose alteplase plus abciximab or direct angioplasty plus abciximab) on fibrinolytic and thrombin generation activities. The effect of reduced-dose alteplase plus abciximab and direct angioplasty plus abciximab on hemostatic factors is unknown. Of 70 patients with acute myocardial infarction of < or = 6 hours, 34 were randomized to reduced-dose alteplase (35 to 50 mg in 1 hour) and 36 to direct angioplasty. A standard bolus and infusion dose of abciximab was administered to all patients. Blood specimens were collected at baseline, and at 1, 4, 12, and 24 hours. The following parameters were assayed: fibrinogen, plasminogen and antiplasmin activities, tissue plasminogen activator antigen, D-dimer, prothrombin fragments F1 + 2, and thrombin/antithrombin III complexes. Among patients treated with reduced-dose alteplase plus abciximab, the fibrinogen level decreased by 28.4% in the first hour (11.7 +/- 3.4 vs 7.8 +/- 2.5 micromol/L, p <0.001). Correspondingly, plasminogen and antiplasmin activities decreased by 43.8% (p <0.001) and 59.1% (p <0.001), respectively. Prothrombin fragments F1 + 2 increased from 2.2 +/- 1.7 to 4.2 +/- 1.6 nmol/L (1 hour) (p <0.001) and thrombin/antithrombin III increased from 16.3 +/- 15.0 to 33.5 +/- 19.9 microg/L (1 hour) (p <0.001). Conversely, in the direct angioplasty group, there was a marginal elevation in fibrinogen level at 1 hour (10.2 +/- 2.4 vs 10.6 +/- 2.0 micromol/L, p = 0.064) despite a significant reduction in plasminogen and an increase in tissue plasminogen activator levels. There was no significant change in prothrombin fragments F1 + 2 and thrombin/antithrombin III levels. Thus, there was considerable fibrinolytic activity with reduced-dose alteplase plus abciximab; thrombin generation was not prevented. Among patients treated with direct angioplasty, there was some endogenous fibrinolytic activity, but there was no significant thrombin generation.

Abciximab↗

PubMed2004

Volumetric analysis of in-stent intimal hyperplasia in diabetic patients treated with or without abciximab: results of the Diabetes Abciximab steNT Evaluation (DANTE) randomized trial.

BACKGROUND: In diabetic patients in the Evaluation of Platelet IIb/IIIa Inhibitor for Stenting (EPISTENT) trial, abciximab reduced target vessel revascularization by approximately 50% compared with placebo. Whether this is a result of a lower restenosis rate caused by inhibition of intimal hyperplasia remains to be defined. METHODS AND RESULTS: The purpose of this study was to determine whether abciximab at the time of stent implantation would reduce in-stent intimal hyperplasia measured by intravascular ultrasound at 6-month follow-up in type 2 diabetics. Ninety-six diabetic patients (96 lesions) who underwent elective stent implantation for a de novo lesion in a native coronary artery were randomly assigned to receive abciximab or no abciximab. In-stent intimal hyperplasia volume, expressed as percentage of stent volume, did not differ between groups: 41.3+/-21.0% for those treated with abciximab versus 40.5+/-18.3% for those treated without abciximab (P=0.9). There were also no significant differences in angiographic minimal luminal diameter at follow-up (1.74+/-0.69 versus 1.66+/-0.63 mm; P=0.5), late loss (1.03+/-0.63 versus 1.07+/-0.58 mm; P=0.7), restenosis rate (17.8% versus 22.9%; P=0.5), or cumulative incidence of major adverse cardiac events at 12 months (19.1% versus 20.4%; P=0.9). CONCLUSIONS: Six-month intravascular ultrasound volumetric analysis showed that abciximab, at the time of coronary stent implantation, was not associated with a reduction of in-stent intimal hyperplasia in diabetic patients.

Abciximab↗