CHICAGO – Bolus intracoronary abciximab delivered directly to the infarct lesion site in patients undergoing primary percutaneous coronary intervention for a large anterior myocardial infarction significantly reduced infarct size at 30 days in the INFUSE-AMI randomized trial.
In contrast, manual aspiration thrombectomy, also studied in INFUSE-AMI, proved to have no impact on infarct size, Dr. Gregg W. Stone reported at the annual meeting of the American College of Cardiology.
INFUSE-AMI was a 37-site, 6-nation prospective clinical trial. It involved 452 patients who presented within 4 hours after onset of symptoms, because of an ST-segment elevation MI involving occlusion of the proximal or midleft anterior descending coronary artery with no or minimal flow.
Participants underwent primary percutaneous coronary intervention (PCI) with bivalirudin anticoagulation. Under the 2 x 2 factorial study design, patients were randomized to aspiration plus a 0.25-mg/kg bolus of intracoronary abciximab, aspiration without abciximab, abciximab with no aspiration, or neither intervention. The goal was to find out whether either or both interventions reduce distal embolization of atherothrombotic debris resulting from primary PCI, which can lead to large infarcts despite prompt revascularization.
The primary endpoint in INFUSE-AMI was infarct size at 30 days as assessed by cardiac MRI. Most prior trials have measured infarct size at 3-5 days, when transitory myocardial edema typically makes the infarcts more than twice as large as they are at 30 days, explained Dr. Stone, director of cardiovascular research and education at Columbia University Medical Center/New York–Presbyterian Hospital.
The median 30-day infarct size in patients who got intracoronary abciximab was 15.1%, compared with 17.9% in those who did not. That’s roughly a 15% relative reduction. The abciximab group also had a significantly smaller median absolute infarct mass: 18.4 g, compared with 24 g. In addition, they showed a trend for a lower abnormal wall motion score that didn’t reach significance.
In contrast, 30-day infarct size and the other endpoints were almost identical, regardless of whether patients got aspiration thrombectomy or not.
The combined rate of TIMI (Thrombolysis in Myocardial Infarction) major or minor bleeding was 2.2% in patients who received intracoronary abciximab and 1.8% in those who did not, a nonsignificant difference.
Dr. Stone said that while it might now be reasonable based on the INFUSE-AMI findings to use an intracoronary bolus of abciximab during primary PCI in a highly select patient subset – those who present early with a particularly large occlusion of the proximal left anterior descending artery and are at low bleeding risk – he doesn’t consider INFUSE-AMI to be a definitive trial.
"The reduction in infarct size, while significant, was modest. Going into the study we considered that an absolute 6% reduction would be clinically relevant. We got about half of that. We really need a large outcomes trial to see if that amount of infarct size reduction improves clinical outcomes," the cardiologist said.
Currently, there are no plans for such a study, since INFUSE-AMI was just completed, and the findings are still being scrutinized. But Dr. Stone indicated that a decision to undertake a big clinical outcomes trial is by no means a slam dunk.
"If you studied 10,000 patients and you had exactly these results, there probably would be a clinical benefit, but it would be modest. And there is the possibility that bleeding would offset some of that," he commented.
Discussant Dr. Erik Magnus Ohman of Duke University, Durham, N.C., noted that a recent report from the AIDA STEMI (Abciximab IV versus IC in ST-Elevation Myocardial Infarction) trial, which with 2,065 randomized patients was powered for clinical outcomes, reported nearly identical infarct sizes and cardiovascular event rates with bolus intracoronary abciximab, compared with intravenous abciximab (Lancet 2012;379:875-7).
Dr. Stone replied that AIDA-STEMI and all other studies prior to INFUSE-AMI had a major limitation: Intracoronary abciximab was infused through the guide catheter. That’s highly inefficient in terms of getting the agent into the thrombus.
"Most of the drug probably goes down the circumflex artery or just blows back into the aorta," he explained.
In contrast, INFUSE-AMI utilized the ClearWay Rx local therapeutic infusion catheter, a low-profile "weeping" balloon that delivers abciximab directly to the infarct lesion.
As for aspiration thrombectomy, a practice now encouraged with a IIb recommendation in the ACC/American Heart Association guidelines, Dr. Stone noted that this intervention is the subject of two ongoing multithousand-patient randomized trials, TOTAL and TASTE, which should provide the final word on this procedure.
"I will say, though, that it’s hard for me to understand how aspiration can work as a routine therapy if it doesn’t decrease infarct size. I would predict that these trials might not be positive," Dr. Stone said.