Abciximab as Adjunctive Therapy to Reperfusion in Acute ST-Segment

Elevation Myocardial Infarction

A Meta-analysis of Randomized Trials

Giuseppe De Luca, MD; Harry Suryapranata, MD, PhD; Gregg W. Stone, MD; David Antoniucci, MD; James E. Tcheng, MD; Franz-Josef Neumann, MD; Frans Van de

Werf, MD; Elliott M. Antman, MD; Eric J. Topol, MD

JAMA. 2005; 293:1759-1765.

ReoPro (Abciximab):

A Glycoprotein IIb/IIIa Receptor Blocker

Mechanism of ActionBinds to the GP IIb/IIIa receptor of platelets inhibiting platelet aggregation by preventing the binding of fibrinogen

Binds to the vitronectin (avb3) receptors on platelets, vessel endothelial cells and smooth muscle cells

Other Parameters • Pharmacokinetics

½ life of about ten minutes, with a second phase half life of about 30 minutesEffects on platelet function can be seen for up to 48 hours after the infusion has been terminated. Low levels of glycoprotein IIb/IIIa receptor blockade are present for up to 15 days after the infusion is terminated.

• Clearance. Abciximab binds tightly to platelets and remains bound for at least 15 days.

• Delivery. IV

• Contraindications. sensitivity to any component of product

active internal bleeding, clinically significant GI or GU bleeding within six weekshistory of CVA within two years administration of oral anticoagulants within seven daysthrombocytopenia known intracranial pathologysevere uncontrolled hypertensionvasculitis

Common Bleeding;  blurred vision; confusion; dizziness, faintness, orlightheadedness when getting up from a lying or sitting position suddenly; sweating; unusual tiredness or weakness 

Less common Black, tarry stools;  bleeding gums;  blood in urine or stools;  pinpoint red spots on skin;  unusual bleeding or bruising 

Rare Chest pain or discomfort;  chills;  cough;  eye pain;  fever;  general feeling ofillness;  headache;  pale skin;  rapid weight gain;  shortness of breath;  slow or irregular heartbeat;  sneezing;  sore throat;  swelling of hands, ankles, feet, or lower legs;  tightness in chest;  tingling of hands or feet;  troubled breathing;  unusual tiredness;  wheezing 

Side Effects

Background on development

• The initial step in the emergence of platelet glycoprotein IIb/IIIa receptor blockade as a valuable adjunct to the practice of interventional cardiology was the appreciation that platelet-rich rather than fibrin-rich thrombosis accounted for many of the acute complications of angioplasty and stenting. The identification of the platelet glycoprotein IIb/IIIa receptor as the final common pathway in platelet aggregation and the subsequent development of a monoclonal antibody to this receptor paved the way for some landmark clinical trials.

Selection Criteria

•PubMed/Medline search of literature from 1990-2004

•All selected studies were randomized, placebo-controlled trials. All patients in a given trial received the same reperfusion treatment (PCI or fibrinolysis). Separate meta-analyses were performed for these two treatment modalities.

•Studies were evaluated by two investigators; disagreements were resolved by consensus.

Question: What standards were used to evaluate the individual studies?

Data Synthesis

•Eleven trialsEight trials in PCI groupThree trials in fibrinolysis group

•27,115 patients12,602 in abciximab group14,513 in control group

3949 patients in PCI group23,166 patients in fibrinolysis group

Copyright restrictions may apply.

De Luca, G. et al. JAMA 2005;293:1759-1765.

Characteristics of Primary Angioplasty and Fibrinolysis Randomized Trials Included in the Meta-analysis

End Points

•Primary•Mortality at 30 days•Mortality at 6 and 12 months

•Secondary•Reinfarction at 30 days

•Safety end points (complications)•Intracranial bleeding•Other major bleeding

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De Luca, G. et al. JAMA 2005;293:1759-1765.

Abciximab and 30-Day Mortality From Fixed-Effects Model

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De Luca, G. et al. JAMA 2005;293:1759-1765.

Abciximab and Long-Term (6- and 12-Month) Mortality From Fixed-Effects Model

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De Luca, G. et al. JAMA 2005;293:1759-1765.

Abciximab and 30-Day Reinfarction

Copyright restrictions may apply.

De Luca, G. et al. JAMA 2005;293:1759-1765.

Funnel Plot of All Studies Included in the Meta-analysis

Final Thoughts

• Potential increased risk of ICB in elderly patients with adjunctive abciximab and fibrionlysis

• Mortality-->prevention of downstream embolization post reperfusion

• Benefit of 1° PCI and Abciximab in cardiogenic shock?

Timing of Admin

• Most trials report drug given right before angioplasty i.e. right before balloon inflation

• ADMIRAL trial: abciximab given to patients in ambulance or ED --> improved outcome and preprocedural perfusion

Shortcomings of Analysis

• More patients received fibrinolysis than PCI in the studies analyzed

• More info on interaction btw and age and ICB

• Awaiting results of large randomized trial looking specifically at PCI and abciximab (at time of publication)

“Where’s the Money?”:

• Until more trials, recommend abciximab with 1°PCI for STEMI in high risk patients, avoid adjunctive therapy with fibrinolysis