INFUSE-AMI: Thirty-Day Reduction in Infarct Size May Translate to 1-Year Benefit

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Intralesional abciximab and thrombus aspiration each appears to improve 1-year outcomes in patients who undergo primary percutaneous coronary intervention (PCI) for anterior ST-segment elevation myocardial infarction (STEMI). But the findings should be considered hypothesis generating only until confirmed by a trial adequately powered for clinical endpoints, says a paper published online October 1, 2013, ahead of print in Circulation: Cardiovascular Interventions.

For the INFUSE-AMI trial, a team led by Gregg W. Stone, MD, of Columbia University Medical Center (New York, NY), enrolled 452 patients who presented within 5 hours of symptom onset with STEMI caused by proximal or mid LAD occlusion. All underwent primary PCI with bivalirudin anticoagulation. Patients were randomized in a 2x2 factorial design to bolus abciximab delivered locally at the infarct lesion site vs. no abciximab and to manual aspiration vs. no aspiration.

Thirty-day follow-up, published last year in the Journal of the American Medical Association, demonstrated that abciximab—but not manual aspiration—significantly reduced infarct size, the primary endpoint. Clinical outcomes were similar across groups at 30 days.

Signs of Benefit up to 1 Year

Between 31 days and 1 year, aspiration was associated with less new-onset severe heart failure and rehospitalization for heart failure as well as a reduced rate of the composite of major adverse cardiac and heart failure events compared with no aspiration. At 1 year, there were no differences in cumulative event rates apart from rehospitalization for heart failure (table 1).

Table 1. Event Rates by Thrombus Aspiration Randomization

Abbreviations: HF, heart failure; MACCE, major adverse cardiac and cerebrovascular events; MACHFE, major adverse cardiac and heart failure events; ST, stent thrombosis; TVR, target vessel revascularization.

In addition, between 31 days and 1 year, abciximab was associated with less death (1.4% vs. 4.9%; P = 0.04) and fewer major cardiovascular and cerebrovascular events (death, reinfarction, stroke, or clinically driven TVR; 3.3% vs. 7.8%; P = 0.04) compared with no abciximab, though by 1 year there were no differences in cumulative event rates.

Median infarct size at 30 days was 17% of total LV mass. Patients with infarct size below that cutpoint had lower 1-year rates of death, new-onset severe heart failure, rehospitalization for heart failure, stent thrombosis, and composite events. A Cox proportional hazards regression model adjusting for age found infarct size to be an independent predictor of 1-year mortality (HR 1.11; 95% CI 1.01-1.22; P = 0.03).

Compared with no treatment, overall the use of abciximab, thrombus aspiration, or both produced lower 1-year rates of death (4.5% vs. 10.4%; P = 0.03), severe heart failure (4.2% vs. 10.3%; P = 0.02), and stent thrombosis (0.9% vs. 3.8%; P = 0.046).

Basis for Future Research

In a telephone interview, Dr. Stone emphasized to TCTMD that INFUSE-AMI was “not powered for clinical endpoints . . . so [the current findings] are just exploratory. . . . We didn’t see a statistically significant difference at 1 year, but there were some trends from 30 days to 1 year that maybe things were looking a little bit better with thrombus aspiration and intralesional abciximab.”

The link between 30-day infarct size and subsequent outcomes is “probably real,” he said. But given that aspiration did not reduce infarct size in the trial, the observed benefit of that treatment evidently comes from another direction, Dr. Stone explained. “You could hypothesize less stent thrombosis by removing some thrombus or possibly less microvascular dysfunction, etc. Also, it really just may be play of chance. You can’t exclude chance with small numbers.”

Dr. Stone asserted that a clinical outcomes trial of intralesional abciximab, which offers higher drug concentrations within the lesion than intracoronary delivery, is warranted. Two ongoing large-scale trials powered for mortality, TASTE and TOTAL, are testing the value of thrombus aspiration before primary PCI.

Trial Inspires Cautious Enthusiasm

Erik Magnus Ohman, MD, of Duke University School of Medicine (Durham, NC), agreed that the INFUSE-AMI trial should be interpreted carefully, given that data from the all-comers TASTE trial presented recently at the European Society of Cardiology Congress showed no reduction in 30-day mortality with aspiration. “And it was a large trial of 7,000 patients. The weakness of [TASTE] is that we can’t look at any secondary endpoints because they’re not adjudicated and are site reported,” he told TCTMD in a telephone interview.

INFUSE-AMI raises the possibility that there may still be a role for manual aspiration, “but it may be only in certain patients. . . . It’s really the large anterior MIs where we can now detect any differences,” Dr. Ohman said. “What we may be getting to is that our treatments are so good that in patients with inferior or small MIs, it’s hard to prove things to be efficacious.”

Aspiration’s positive effect on 1-year rates of readmission for heart failure is particularly notable, he commented. “The fact that you can modulate an endpoint that we believe is a very important one from the patient perspective—no one wants to go to the hospital—is an important observation,” he said.

Study Details

Abciximab was administered locally in a single bolus dose (0.25 mg/kg) at the infarct lesion using the Clearway RX catheter (Atrium Medical, Hudson, NH), and thrombus aspiration was performed using the 6-Fr Export catheter (Medtronic, Santa Rosa, CA).

Note: Dr. Stone and several coauthors are faculty members of the Cardiovascular Research Foundation, which owns and operates TCTMD.

 

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Source:
Stone GW, Witzenbichler B, Godlewski, J, et al. Intralesional abciximab and thrombus aspiration in patients with large anterior myocardial infarction: One-year results from the INFUSE-AMI trial. Circ Cardiovasc Interv. 2013;Epub ahead of print.

 

 

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