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Assessment of markers of myocardial damage by cardiac magnetic resonance (CMR) imaging shows no difference between intracoronary and intravenous (IV) abciximab in patients with ST-segment elevation myocardial infarction (STEMI). Results from a substudy of the AIDA- STEMI trial were published online February 27, 2013, ahead of print in the Journal of the American College of Cardiology.

The findings were originally presented at the annual Transcatheter Cardiovascular Therapeutics scientific symposium in October 2012 in Miami, FL.

The multicenter AIDA-STEMI trial, which randomized 2,065 patients presenting within 12 hours of STEMI to intracoronary or IV bolus abciximab during primary PCI, showed no difference in the composite primary endpoint of all-cause mortality, recurrent MI, or new congestive heart failure at 90 days.

For the prespecified subanalysis, investigators led by Holger Thiele, MD, of the University of Leipzig Heart Center (Leipzig, Germany), looked at 795 patients from 8 sites who underwent CMR imaging within 10 days of the index event.

CMR Parameters Assessed

Infarct size and myocardial salvage index (relation of final infarct size to myocardium at risk) were similar between the intracoronary and IV groups. In addition, no differences were seen in the occurrence or extent of late microvascular obstruction, intramyocardial hemorrhage, or LVEF (table 1).

Table 1. CMR Results

Multiple subgroup analyses likewise turned up no differences between the intracoronary and IV arms.

In multivariate regression analysis, predictors of infarct size included:

• Systolic blood pressure (P < 0.001)
• Killip class on admission (P < 0.001)
• Time from symptom onset to PCI hospital admission (P < 0.001)
• TIMI flow before PCI (P < 0.001)
• LAD lesion (P = 0.03)

At 12-month follow-up, there was no difference in rates of death, reinfarction, or congestive heart failure between the intracoronary and IV groups, resulting in a similar incidence of MACE (6.2% vs. 7.3%; P = 0.53).

However, on average, patients who experienced MACE had larger infarcts, less myocardial salvage, and more pronounced LV dysfunction (table 2).

Table 2. Relationship of CMR Markers and Clinical Outcomes at 12 Months

According to the authors, “the main mechanism through which intracoronary abciximab may improve myocardial perfusion and clinical outcomes is the higher drug concentration, resulting in increased local platelet inhibition, displacement of platelet-bound fibrin, and dissolution of thrombi.” In fact, some previous studies have shown the superiority of intracoronary delivery for surrogate endpoints, they report. However, the main AIDA-STEMI trial, which was powered for clinical endpoints, failed to find a difference between the drug delivery strategies, and the current analysis reinforces that finding by showing no biological basis for one, they add.

But because the current study linked patient risk profile to mortality, Dr. Thiele and colleagues say, “there are still open questions worth studying such as the appropriate patient group (eg, exclusively high-risk patients with high thrombus burden and large myocardium at risk), the means of intracoronary abciximab administration (role of selective delivery systems), and concomitant medication.”

In an accompanying editorial, John A. Bittl, MD, of the Ocala Heart Institute (Ocala, FL), observes that “[r]efinements in the use of oral antiplatelet agents and bivalirudin have narrowed the indications for abciximab during PCI for STEMI. The decision to use abciximab . . . can be guided in part by the adequacy of concurrent therapy with aspirin and P2Y12 receptor blockers.”

When such therapy has a high risk of failure or cannot be given before primary PCI, abciximab is called for, Dr. Bittl says, specifying that “[i]n high-risk situations such as stent thrombosis or extensive intracoronary thrombus, [intracoronary] abciximab may be preferable to IV abciximab.”

Any Possible Benefit Likely Small

In a telephone interview with TCTMD, Sorin J. Brener, MD, of Weill Cornell Medical College (New York, NY), concurred that while “there may be some patients in whom intracoronary abciximab is appropriate—eg, those with a large thrombus burden and potentially larger area of myocardium at risk—in general there is no need to use it.”

As for why the INFUSE-AMI trial (Stone GW, et al. JAMA. 2012;307:1817-1826) yielded positive results with intracoronary abciximab and AIDA-STEMI did not, Dr. Brener cited 2 differences. First, INFUSE-AMI investigators used dedicated delivery balloons, which provided a higher drug concentration in the vicinity of the clot, enhancing platelet disaggregation. Second, and more important, he noted, all INFUSE-AMI patients had large, anterior-wall MIs.

“Even so,” Dr. Brener added, “the benefit was very small in absolute terms. AIDA-STEMI shows that when you dilute anterior wall patients with people with small MIs, you don’t see any benefit overall.”

In addition, he called the assessment of infarct size in AIDA-STEMI within the first 10 days after the event “somewhat problematic.” Since the infarct shrinks over time (much of it is edema), it would have been considerably smaller if measured at 30 days, as was done in INFUSE-AMI, he noted.

However, AIDA-STEMI’s finding of a connection between myocardial damage and MACE is important, Dr. Brener commented. “People with MACE had 50% larger infarcts than those without MACE,” he noted. “That confirms the prognostic value of infarct size, and suggests that MACE are in fact mediated by infarct size.”

Even if future, more focused research identifies some benefit of intracoronary abciximab, it will undoubtedly be very small, Dr. Brener suggested. “In that respect, I think INFUSE-AMI clarifies the issue,” he said, “because when you take the population at the highest possible risk—meaning larger anterior wall MIs—and you compare intracoronary abciximab delivered under optimal conditions with placebo and there’s still only a reduction in infarct size of 2%, it’s hard to get excited about it.”

Study Details

Baseline characteristics for the groups were similar except for a higher prevalence of hypertension in intracoronary patients and of previous bypass surgery in IV patients.

Sources:

1. Eitel I, Wöhrle J, Suenkel H, et al. Intracoronary compared with intravenous bolus abciximab application during primary percutaneous coronary intervention in ST-segment elevation myocardial infarction: Cardiac magnetic resonance substudy of the AIDA STEMI trial. J Am Coll Cardiol. 2013;Epub ahead of print.
2. Bittl JA. Abciximab during percutaneous coronary intervention for ST-segment elevation myocardial infarction: Intracoronary, intravenous, or not at all? J Am Coll Cardiol. 2013;Epub ahead of print.

Related Stories:

• AIDA-STEMI Substudy Confirms Original Findings
• AIDA STEMI: No Advantage for Intracoronary vs. Intravenous Abciximab
• Meta-analysis Favors Intracoronary vs. Intravenous Abciximab in Primary PCI