Meta-analysis: Intracoronary vs. IV Abciximab Improves Survival in STEMI Patients

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Compared with standard intravenous administration, intracoronary delivery of the glycoprotein IIb/IIIa inhibitor abciximab can improve survival without increasing the risk of major bleeding in patients with ST-segment elevation myocardial infarction (STEMI), researchers conclude in a study published online October 11, 2011, ahead of print in Platelets.

Giuseppe De Luca, MD, of the University of Eastern Piedmont (Novara, Italy), and colleagues conducted a meta-analysis of 6 trials totaling 1,246 patients who were randomized to intracoronary (n = 636) or IV abciximab (n = 610). All were single-center trials published between 2008 and 2011 with symptom onset from less than 6 hours to 12 hours before the procedure.

At 30 days, intracoronary abciximab was associated with a significant reduction in mortality, which was the primary endpoint, as well as target vessel revascularization (TVR). There was no significant difference in other secondary endpoints between the 2 treatment groups (table 1).

Table 1. Primary and Secondary Endpoints

30-Day Outcomes

Intracoronary
(n = 636)

IV
(n = 610)

HR
(95% CI)

P Value

Mortality

1.4%

3.3%

0.43
(0.20-0.94)

0.03

TVR

2.7%

4.9%

0.53
(0.29-0.99)

0.05

Recurrent MI

1.4%

2.5%

0.54
(0.23-1.28)

0.17

Major Bleeding

2.9%

3.2%

0.91
(0.46-1.79)

0.79


In sensitivity analysis, no single study was found to influence the overall results in terms of safety or efficacy endpoints.

Intracoronary Administration Advantages

According to the study authors, intracoronary abciximab offers advantages over the IV route primarily due to the high local concentrations at the site of the clot, which induce platelet disaggregation along with destabilization and remodeling of the thrombus.

“Moreover, at high concentrations, abciximab exerts some [glycoprotein] IIb/IIIa receptor-independent effects such as inhibition of plasminogen activator inhibitor-1 and [alpha] 2-anti-plasmin release as well as complex interactions with [alpha]Vb3 vitronectin and Mac-1 receptors,” they write. “Modulating multiple pathways, abciximab is believed to decrease the inflammatory response in the injured endothelium, hence reducing platelet aggregation, thrombin generation, and intimal hyperplasia.”

However, whether such mechanisms translate into further clinical benefits is still unclear, they say. Another unknown is whether there is benefit to using abciximab in combination with thrombectomy. The randomized trials in the meta-analysis showed considerable variability in the practice of thrombectomy.

“The question whether thrombus aspiration combined with local glycoprotein IIb/IIIa [inhibitor] administration exerts a synergistic effect to reduce the infarct size in STEMI patients undergoing [primary PCI] has not been answered yet,” Dr. De Luca and colleagues write.

Larger Studies on the Horizon

In a telephone interview with TCTMD, Gregg W. Stone, MD, of Columbia University Medical Center (New York, NY), cautioned that larger studies are needed to definitively demonstrate impact on mortality since most of the 6 randomized trials in the meta-analysis were fairly small, the largest being the CICERO trial with 271 patients.

“Nonetheless,” Dr. Stone said, “this meta-analysis is hypothesis generating along with other studies that have shown possible improvements in myocardial salvage with this approach, presumably due to less distal embolization and microvascular obstruction.”

Two other large-scale randomized trials currently are looking at whether intracoronary abciximab can improve outcomes in STEMI patients, Dr. Stone added. The largest of these is the AIDA STEMI (Abciximab Intracoronary versus intravenously Drug Application in ST-Elevation Myocardial Infarction) trial, with more than 2,000 patients and a composite endpoint of death, reinfarction and new congestive heart failure at 90 days. Those results are scheduled for presentation at the 2011 American Heart Association Scientific Sessions in Orlando, FL, sthis month.

The other large trial, INFUSE-AMI, which Dr. Stone is investigating, is a mechanistic study in which STEMI patients are randomized based on local/no infusion of abciximab with or without aspiration. The patients are also receiving bivalirudin for anticoagulation.

“It’s thought that by giving the drug directly into the clot itself, that may even further increase the local concentration of abciximab,” he said. “This will hopefully allow us to preserve the bleeding advantages of bivalirudin but have the decreased embolization and improved myocardial perfusion of the bolus intracoronary abciximab.”

Results of INFUSE-AMI will be presented at the 2012 American College of Cardiology Annual Scientific Session, Dr. Stone said.

 


Source:
Navarese EP, Kozinski M, Obonska K, et al. Clinical efficacy and safety of intracoronary vs. intravenous abciximab administration in STEMI patients undergoing primary percutaneous coronary intervention: A meta-analysis of randomized trials. Platelets. 2011;Epub ahead of print.

 

 

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Disclosures
  • Dr. De Luca reports no relevant conflicts of interest.
  • Dr. Stone reports serving as a consultant to Abbott Vascular, Atrium, Boston Scientific, Eli Lilly-Daiichi Sankyo, and Medtronic.

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