Abciximab: a reappraisal of its use in coronary care

Figures & data

Table 1 Pharmacological data of principal GPIIb/IIIa inhibitors

Parameter	Abciximab	Tirofiban	Eptifibatide
Molecular weight (Da)	∼50000	∼490	∼800
Receptor selectivity
GPIIb/IIIa	High	High	High
MAC-1	High	No	No
Molecular mechanism	Monoclonal antibody with high affinity for GPIIb/IIIa receptor	Competitive inhibitor	Competitive inhibitor
Clearance	Platelet binding	Renal (60%) + biliar (40%)	Renal (90%)
Half-life (h)
plasma	0.5	2	3
platelet	4	No	No
Dissociation constant (nmol/L)	∼5	∼15	∼120
Antigenicity	Possible	No	No
Reversibility of effect (h)	72–96	4	4–6

Table 2 Abciximab use in clinical trials

Trials	Population study	Design	Key information
EPIC	2099 pts scheduled to high risk PCI	Placebo vs only bolus abciximab vs bolus + infusion abciximab	Abciximab bolus + infusion resulted in a 35% reduction in the rate of the primary endpoint
EPISTENT	2399 pts receiving elective or urgent PCI	Stent and placebo vs stent and abciximab vs POBA and abciximab	Abciximab and stent implantation confer complementary long-term clinical benefits
EPILOG	2792 pts receiving elective or urgent PCI	Heparin vs abciximab + heparin vs abciximab + low-dose heparin	Reduction of acute ischemic complications, without increasing the risk of hemorrhage
CAPTURE	1050 pts with refractory UA	Abciximab vs placebo. PCI was scheduled 18–24 h after medication	Abciximab substantially reduces the rate of MI, before, during, and after PCI
GUSTO IV-ACS	7800 patients with ACS	Placebo (heparin) vs abciximab bolus + infusion for 24 h vs abciximab bolus + infusion for 48 h	No difference in 30-day death or MI in main cohort and diabetic subgroup analysis fails to reach statistical significance
TARGET	5308 patients scheduled to PCI	Tirofiban (RESTORE regime) vs abciximab	Lower incidence of death, re-MI, and TVR in the abciximab group
ISAR-REACT	Pts low risk undergoing PCI	600 mg clopidogrel vs 600 mg clopidogrel + abciximab	Abciximab offered no clinically measurable benefit at 30 days
ISAR-REACT 2	2022 pts with ACS undergoing PCI	600 mg clopidogrel vs 600 mg clopidogrel + abciximab	Reduction of the risk of adverse events in patients with non-STsegment elevation ACS

Abbreviations: ACS, acute coronary syndrome; MI, myocardial infarction; PCI, percutaneous coronary intervention; POBA, percutaneous only ballon angioplasty; pts, patients; TVR, target vessel revascularization; UA, unstable angina.

Figure 1 Incidence of myocardial infarction in the two study groups of TARGET trial (Topol et al 2001).

Figure 2 Percentage of patients in whom >80% inhibition of 20 mol/L ADP-induced platelet aggregation was achieved. At 15 minutes, inhibition was significantly higher in abciximab and eptifibatide groups as compared to tirofiban RESTORE group. At 12 hours, inhibition was significantly higher in eptifibatide and tirofiban RESTORE groups as compared to abciximab group. Adapted with permission from Batchelor WB, Tolleson TR, Huang Y, et al 2002. Randomized comparison of platelet inhibition with abciximab, tirofiban and eptifibatide during percutaneous coronary intervention in acute coronary syndromes. The COMPARE Trial. Circulation, 106:1470. Copyright © 2002 Lippincott Williams & Wilkins.

Table 3 Indication to use abciximab according to current guidelines

Class	ACC/AHA guidelines	European task force report
I	For NSTEACS patients in whom an initial invasive strategy is selected. Abciximab is indicated only if there is no appreciable delay to angiography and PCI is likely to be performed. For high risk NSTEACS patients in whom PCI has been selected as a post-angiography management strategy, it is reasonable administer abciximab if a GP IIb/IIIa has not been started before diagnostic angiography.	High risk NSTEACS patients not pretreated with GP IIb/IIIa inhibitors and proceeding PCI.
II	It is reasonable to start treatment with abciximab as early as possible before primary PCI (with or without stenting) in patients with STEMI. Abciximab administration in high risk NSTEACS patients in whom bivalirudin was selected as anticoagulant.	Abciximab as ancillary therapy during primary PCI. Stable CAD patients treated with PCI of complex lesions, threatening/actual vessel closure, visible thrombus, no/slow reflow. When anatomy is known and PCI planned to be performed whitin 24 hours with GPIIb/IIIa inhibitors, most secure evidence is for abciximab.
III	Abciximab administration in ACS patients in whom PCI is not planned.	Abciximab is in fact unnecessary in patients treated with a non invasive strategy.

Abbreviations: ACC, American College of Cardiology; ACS, acute coronary syndrome; AHA, American Heart Association; PCI, percutaneous coronary intervention; NSTEACS, non ST-segment elevation acute coronary syndrome; STEMI, ST-segment elvation myocardial infarction.

Table 4 Contraindications to abciximab use

Absolute contraindications

Intracranial aneurysm

Artery-venous malformation

Active major bleeding

Coagulopathy (eg, hemophilia)

Intracranial mass

Stroke in the previous 30 days

Hemorrhagic stroke

Surgery or trauma in the preceding 6 weeks

Thrombocytopenia

Concurrent dextran therapy

Murine protein hypersensitivity

Vasculitis

Relative contraindications

Concurrent anticoagulation therapy (eg, with warfarin)

Breast feeding

Pregnancy

Uncontrolled hypertension (SBP >200 mmHg, DBP >110 mmHg)

Thrombolytic therapy

Abciximab hypersensitivity

Abbrevations: DBP, diastolic blood pressure; SBP, systolic blood pressure.

TopolEMoliternoDHerrmannH2001Comparison of two platelet glycoprotein IIb/IIIa inhibitors, tirofiban and abcix imab, for the prevention of ischemic events with percutaneous coronary revascularizationN Engl J Med344188811419425

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BatchelorWBTollesonTRHuangY2002Randomized comparison of platelet inhibition with abciximab, tirofiban and eptifibatide during percutaneous coronary intervention in acute coronary syndromes. The COMPARE TrialCirculation106147012234950

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