OBJECTIVE: To review the scientific literature on the pharmacology and clinical uses of abciximab. DATA SOURCES: MEDLINE, Index Medicus, and bibliographic literature searches of English-language articles pertaining to abciximab, 7E3, m7E3, and c7E3 were performed. Eli Lilly also provided unpublished results of the Evaluation of 7E3 for the Prevention of Ischemic Complications trial. DATA SELECTION: The selection of data presented focused on controlled trials using abciximab at doses currently approved by the Food and Drug Administration. DATA SYNTHESIS: Abciximab is a humanized chimeric Fab fragment of 7E3. 7E3 is a murine antibody directed against the integrin glycoprotein IIb)/IIIa receptor (GPIIb/IIIa) located on platelets. These receptors play an integral part in platelet aggregation by allowing fibrinogen to bind to them and interconnect platelets. When administered intravenously, abciximab binds to GPIIb/IIIa and hinders platelet aggregation. Bleeding times and activated clotting times are increased and the platelets' response to adenosine diphosphate is reduced with the use of abciximab. Clinical trials have indicated that abciximab can reduce the incidence of abrupt closure and restenosis associated with percutaneous transluminal coronary angioplasty (PTCA) performed in high-risk patients. Clinical trials also suggest that abciximab may have a role in the treatment of unstable angina and the acute therapy of myocardial infarctions. Complications associated with abciximab include bleeding and thrombocytopenia. The thrombocytopenia is likely related to immunologic mechanisms. In addition, the production of antimurine antibodies has been demonstrated with abciximab use. Abciximab is currently approved for the prevention of abrupt coronary closure associated with PTCA in patients at high risk for this event. CONCLUSIONS: Abciximab is effective in preventing platelet aggregation and has been proven to be of clinical benefit in selected high-risk patients receiving PTCA.

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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.

CRD COMMENTARY: The search is limited to English language articles and the number of trials found is small. It is, therefore, difficult to be certain of the generalisability of the review's conclusions.

OBJECTIVE: To estimate the cost per ischaemic event (death, nonfatal myocardial infarction, subsequent revascularisation procedure) avoided at 6 months in high risk patients undergoing coronary revascularisation treated with abciximab during routine medical care. DESIGN: Retrospective, matched cohort design. SETTING: University teaching hospital. PATIENTS: 62 abciximab-treated patients and 62 patients not treated with abciximab with high risk coronary lesions were matched according to gender, hyperlipidaemia, diabetes mellitus and stenting. MAIN OUTCOME MEASURES: Using a third-party payer's perspective, an incremental cost-effectiveness ratio (ICER) was computed as the cost per ischaemic event avoided over 6 months. Fieller's theorem was used to estimate confidence sets and confidence ellipses were generated to visually represent the variability in the data. RESULTS: At 6 months, abciximab-treated patients experienced an approximately 40% lower rate of ischaemic events (16.1 vs 27.4%; p = 0.128). The point estimate of the ICER was $US21,789 per ischaemic event avoided. Fieller's theorem resulted in a 95% confidence set consisting of 2 half-lines (-infinity to -$US115,461) and ($US391 to +infinity), reflecting the finding that the ICER denominator was not significantly different from zero at the p = 0.05 level. CONCLUSIONS: In high risk patients treated during routine care, the effectiveness of abciximab was consistent with efficacy rates from clinical trials. However, abciximab-treated patients remained approximately $US2400 more costly at 6 months.

BACKGROUND: Abciximab is a monoclonal antibody that prevents platelet aggregation by blocking platelet glycoprotein (GP) IIb/IIIa receptor. OBJECTIVE: To study the safety profile of this agent in contemporary clinical practice. METHODS: We evaluated efficacy and safety end points (major and minor bleeding, thrombocytopenia) in patients treated with abciximab and compared them to those treated with placebo in main randomized clinical trials of patients with acute coronary syndromes (ACS) or those undergoing percutaneous coronary intervention (PCI). RESULTS/CONCLUSION: Use of abciximab is associated with an improved outcome in high-risk patients undergoing PCI but with a worse outcome in ACS patients treated conservatively. Use of abciximab is associated with an acceptable safety profile even when used on a background of aspirin and high doses of thienopyridine but has a potential to increase thrombocytopenia and minor bleeding. Small molecule GP IIb/IIIa antagonists are increasingly preferred over abciximab in clinical practice, and recent observational data have demonstrated these agents to have a similar efficacy and safety profile. As an increasing number of agents are being evaluated for peri-PCI anti-thrombotic therapy, the role of abciximab is likely to be further restricted to the highest risk patients.

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BACKGROUND:Patients with acute myocardial infarction might benefit from the addition of glycoprotein IIb/IIIa inhibitors to fibrinolytic or mechanical reperfusion strategies. We compared two strategies, stenting and fibrinolysis, both combined with abciximab, in terms of their ability to salvage myocardium in patients with acute myocardial infarction. METHODS: We enrolled 162 patients with acute myocardial infarction within 12 h of onset of symptoms, assigning 81 stenting plus abciximab and 81 alteplase plus abciximab. Technetium-99m sestamibi scintigraphy was done at admission and after a median of 11 days to calculate initial perfusion defect, final infarct size, and degree of myocardial salvage. The primary endpoint was the salvage index (the ratio of the degree of myocardial salvage to the initial perfusion defect). Major adverse clinical events within 6 months from randomisation were also compared between the two treatments. FINDINGS: Paired scintigraphic measurements were available for 70 patients in the stent group and 71 in the alteplase group. Stenting was associated with greater myocardial salvage than alteplase (median 13.6% [IQR 5.9-23.9] vs 8.0% [2.5-16.0] of the left ventricle; p=0.007). Salvage index was greater in the stent group than in the alteplase group (median 0.60 [0.37-0.82] vs 0.41 [0.13-0.58]; p=0.001). The 6-month mortality rate was 5% (four deaths) in the stent group and 9% (seven deaths) in the alteplase group (relative risk 0.56 [95% CI 0.17-1.88]; p=0.35). INTERPRETATION: In patients with acute myocardial infarction, a reperfusion strategy based on stenting with abciximab produced more myocardial salvage than the combination of fibrinolysis plus abciximab. Larger studies are needed to assess whether these effects translate into clinical benefit.

OBJECTIVE: To assess the cost-effectiveness of abciximab therapy versus traditional practice in high-risk patients receiving percutaneous transluminal coronary angioplasty (PTCA) from a Canadian hospital perspective. DESIGN: A predictive decision analytic model using published clinical and economic evaluations, as well as costs of medical care in Canada. SUBJECTS: High-risk PTCA patients as defined by the Evaluation of c7E3 for Prevention of Ischemic Complications trial and the c7E3 Fab Antiplatelet Therapy in Unstable Refractory Angina trial. INTERVENTIONS: Two treatment strategies were compared: (1) abciximab 0.25 mg/kg intravenous bolus 10 minutes prior to PTCA followed by abciximab 10 micrograms/min intravenous infusion for 12 hours after the procedure, and (2) no abciximab adjunctive therapy at the time of PTCA. Both treatment strategies were combined with intravenous heparin up to 100 units/kg bolus pre-PTCA followed by bolus doses for 1 hour after PTCA per the protocol. Cumulative outcomes were considered up to 6 months after initial PTCA. RESULTS: At 6 months, 29% of the patients in the abciximab treatment arm compared with 33% in the no abciximab arm achieved one of the primary events. The most common adverse event experienced was major bleeding at 4% in the abciximab treatment arm versus 1.6% in the no abciximab arm. The average cost per patient for each strategy was $3261 Can ($1 Can = $0.686 US) (abciximab arm) versus $2073 Can (no abciximab arm), resulting in an incremental cost-effectiveness ratio of $29,700 Can per event-free patient. In univariate sensitivity analyses, the only controllable factor that changed the results of the cost-effectiveness outcome was the cost of abciximab. CONCLUSIONS: Although the use of abciximab as an adjunct to PTCA results in a reduction in event rates in high-risk patients compared with traditional treatment, there is an increased cost associated with this strategy.

BACKGROUND AND PURPOSE: Abciximab is a potent parenterally administered platelet glycoprotein IIb/IIIa antagonist. Because this agent has been shown to improve outcomes in coronary artery disease, there is interest to evaluate whether it could improve cerebral perfusion and outcomes after ischemic stroke. This study was designed to evaluate the safety of abciximab in acute ischemic stroke and to obtain pilot efficacy data. METHODS: We conducted a randomized, double-blind, placebo-controlled, dose-escalation trial. Seventy-four eligible and consenting patients presenting within 24 hours after ischemic stroke onset at 38 study sites were randomly allocated to receive either an escalating dose of abciximab (54 patients) or placebo (20 patients) in a ratio of 3:1. We studied 4 escalating doses of abciximab. Patients underwent a scheduled follow-up head CT scan 24 to 36 hours after the completion of study agent administration to monitor for bleeding complications and were evaluated through 3 months. RESULTS: There were no cases of major intracranial hemorrhage. Asymptomatic parenchymal hemorrhages were detected on post-study agent CT in 4 of 54 abciximab patients (7%) and in 1 of 20 placebo patients (5%). Six additional abciximab patients had asymptomatic hemorrhagic lesions detected by unscheduled brain imaging during their follow-up period. Nine of 11 patients with asymptomatic hemorrhage had a baseline National Institutes of Health Stroke Scale score >14. At 3 months, there was a trend toward a higher rate of minimal residual disability (Barthel Index > or =95 or modified Rankin scale < or =1) among abciximab patients compared with those who received placebo. CONCLUSIONS: Abciximab appears to be safe when administered up to 24 hours after stroke onset, and it might improve functional outcome.