INFUSE-AMI: Intracoronary Abciximab, Not Thrombectomy, Reduces Infarct Size

March 25, 2012

Updated March 25, 2012 (Chicago, Illinois) — The intracoronary administration of abciximab (ReoPro, Eli Lilly) delivered to the infarct lesion site resulted in a significant, albeit modest, reduction in infarct size in patients presenting with a large anterior ST-segment elevation MI (STEMI), whereas the use of aspiration thrombectomy failed to have any demonstrable effect on myocardial infarct size. At 30 days, neither intracoronary abciximab nor thrombectomy improved myocardial reperfusion, ST-segment resolution, or 30-day clinical event rates.

The study, known as INFUSE-AMI, was presented today during the late-breaking clinical-trials session at the American College of Cardiology 2012 Scientific Sessions and published online in the Journal of the American Medical Association to coincide with the presentation.

Speaking with the media during a morning press conference, lead investigator Dr Gregg Stone (Columbia University, New York) said the reduction in infarct size at 30 days with abciximab was approximately half what they had estimated when designing the trial--2.3% vs the hypothesized 6.0% reduction--so larger studies will be needed to determine whether the degree of reduction obtained with the intracoronary infusion of abciximab translates into improved clinical outcomes without a significantly increased risk of bleeding.

Regarding aspiration thrombectomy, Stone said, "It's hard for me to understand how aspiration can work as a routine therapy if it doesn't reduce infarct size."

Testing Relevant Clinical Questions

The INFUSE-AMI study is a 2x2 factorial, randomized, multicenter, single-blind study of a single 0.25-mg/kg bolus of intracoronary abciximab administered at the site of the infarct lesion vs no abciximab and manual aspiration thrombectomy vs no thrombectomy. Over a two-year period, 452 patients from 37 sites in six countries presenting within four hours of STEMI due to a proximal or mid-left anterior descending artery occlusion were included in the study. All patients underwent PCI and received procedural anticoagulation with bivalirudin (Angiomax, the Medicines Company). Stone noted that many of these left anterior MI patients have infarctions of the left ventricle, and these large heart attacks often lead to heart failure.

Cardiac magnetic resonance imaging (cMRI) was used to assess wall motion and infarct size. The primary and secondary efficacy end point was infarct size at 30 days in patients assigned to intracoronary abciximab and manual aspiration thrombectomy, respectively.

Patients randomized to intracoronary abciximab had a significant reduction in the primary end point compared with patients who did not receive abciximab. Infarct size measured as a percentage of total left ventricular mass was 15.2% in the abciximab-treated patients compared with 17.5% in those who did not receive abciximab, a significant 2.3% absolute difference in infarct size (p=0.03).

During the morning press conference, Stone said the while physicians are excellent in getting the infarct artery open in a timely manner in patients with STEMI, there are still many patients with large MIs who go on to develop heart failure. Previous studies testing intracoronary abciximab delivered the drug via the guide catheter, but given the occluded artery, Stone said the thrombus might not have received sufficient abciximab to be effective.

"We used a device called the ClearWay Rx catheter [Atrium, Hudson, NH], which is like a weeping balloon," said Stone. "The drug comes with the balloon and weeps out. You put the balloon right at the site of the blockage, in the blockage itself, so really all the abciximab gets to the site of the infarct lesion and the thrombus."

Not the End of the Story for Thrombectomy

Regarding the thrombus aspiration arm, the investigators reported no difference in infarct size between patients undergoing manual aspiration thrombectomy and those who didn't receive thrombectomy. In both arms, there was no difference in the abnormal wall-motion scores among those who received treatment and those who did not. The lack of effect on infarct size contrasts with the positive one-year results from the Thrombus Aspiration During Percutaneous Coronary Intervention in Acute Myocardial Infarction (TAPAS) study showing that aspiration reduced mortality. Stone pointed out, however, that the TAPAS investigators did not observe a reduction in infarct size at 30 days. Other clinical trials, namely the TOTAL and TASTE studies, are also studying the safety and efficacy of manual aspiration thrombectomy in patients with STEMI.

Speaking with heartwire , Dr Sanjit Jolly (McMaster University, Hamilton, ON), the lead investigator of the TOTAL trial, noted that INFUSE-AMI was a smaller trial and not designed to show any differences in clinical end points. In addition, he said that it is often difficult for an intervention to show a difference in myocardial infarct size. While it is a surrogate end point, Jolly said relationship between infarct size and clinical events is not firmly established.

"It really emphasizes for me that we need to do large outcome trials, especially for a therapy that has a class IIa recommendation," said Jolly. "Either it should be a class I indication, if it really works, or if it doesn't work, then it might need to be downgraded."

To heartwire , Dr Stefan James (Uppsala University Hospital, Sweden), the lead investigator of the TASTE study, said he was a little surprised by the lack of benefit with thrombus aspiration in INFUSE-AMI, given that patients included were considered high risk. That said, he stressed that the evidence is still too scarce to make definitive assessments about its role in clinical practice. The TASTE study is planning on enrolling 5000 patients with STEMI, and all-cause mortality at 30 days is the primary end point. The TOTAL study is enrolling 4000 patients with STEMI, and the primary end point is a composite of cardiovascular death, recurrent MI, cardiogenic shock, or new or worsening NYHA class 4 heart failure at six months.

Stone reports having served as a consultant for Medtronic, Osprey, Reva, Merck, Abbott Vascular, Boston Scientific, Evalve, AstraZeneca, Eli Lilly-Daiichi Sankyo partnership, Bristol-Meyers Squibb-Sanofi partnership, Otsuka, the Medicines Company, Ortho-McNeil, Atrium, Gilead, InspireMD, TherOx, Volcano, InfraReDx, Genentech, GlaxoSmithKline, Miracor, MPP Group, and Lutonix; having received honoraria from Edwards and Vascular Solutions; and holding stock or options from CoreValve, Savacor, Biostar I and II funds, MedFocus I, II, and Accelerator funds, Caliber, Flowcardia, Mediguide, Guided Delivery Systems, Ovalum, Arstasis, Micardia, Access Closure, Embrella, and VNT.

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