INFUSE-AMI: Intracoronary Abciximab in STEMI Patients
- Volume 20 - Issue 5 - May 2012
- Posted on: 5/2/12
- 0 Comments
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The INFUSE-AMI [Intracoronary Abciximab Infusion and Aspiration Thrombectomy in Patients Undergoing Percutaneous Coronary Intervention for Anterior ST Segment Elevation Myocardial Infarction (MI)] trial, a prospective, randomized, single-blind trial conducted at 37 clinical sites in the U.S. and five European countries, enrolled 452 patients who presented within four hours of an anterior wall STEMI. Study subjects were randomized to one of four study arms:
- Intracoronary infusion of abciximab via the ClearWay RX Local Therapeutic Infusion Catheter (Atrium Medical, Hudson, New Hampshire) with thrombus aspiration;
- Intracoronary infusion of abciximab via ClearWay RX without thrombus aspiration;
- Thrombus aspiration only;
- No abciximab infusion and no thrombus aspiration (traditional PCI).
Study endpoints included impact on infarct size at 30 days as measured by cardiac MRI, ST-segment resolution, myocardial perfusion, impact on thrombus burden, and outcomes on bleeding.
The INFUSE-AMI trial was led by the Cardiovascular Research Foundation in New York. Dr. Stone was the principal investigator and Dr. C. Michael Gibson, chief of clinical research at Beth Israel Deaconess Medical Center/Harvard Medical School in Boston, served as co-principal investigator.
What is the problem in STEMI patients that led to INFUSE-AMI?
In patients with a ST-segment myocardial infarction, we have become good at opening the infarct artery very quickly with primary angioplasty and restoring normal epicardial flow to the occluded coronary artery on the surface of the heart. However, the goal of angioplasty is to restore normal myocardial metabolism in the myocardial cells, which are experiencing ongoing injury that will lead to death if that process is not aborted. While we can restore TIMI-3 flow in >90% of patients with primary percutaneous coronary intervention (PCI), and while we can accomplish this rapidly, often we do not salvage as much of the left ventricular myocardium as we would like. This means patients end up with a large infarct and we have an increasing number of patients with heart failure, who are prone to late, sudden death or death from left ventricular failure.
In most cases, what causes a heart attack is the rupture of a thin-capped fiberatheroma overlying a necrotic core. In the necrotic core are soft cholesterol and cholesterol esters, and necrotic cells. As the fiberatheroma ruptures, the necrotic core releases its very pro-thrombotic content to the bloodstream, and that causes a thrombus to form. When the thrombus occludes the vessel, it causes a heart attack. As balloon angioplasty is performed and especially when we put a stent right in the center of the thrombus and the very soft, necrotic core, some of that material is embolized downstream. Sometimes it passes through the capillary system and then it does not do any damage, but many times this material will actually cause capillary block, decreasing myocardial reperfusion. This means even if we see epicardial reperfusion, the blood, oxygen and nutrients are not getting to the heart muscle itself, so normal metabolism cannot be restored.
Many approaches exist to try to improve myocardial salvage and reduce infarct size in patients with evolving heart attack. Two of those approaches revolve around trying to prevent distal embolization of thrombus and soft atheromatus debris from the infarct artery: thrombus aspiration and intracoronary abciximab. Thrombus aspiration uses basically a hollow catheter to extract the thrombus and other soft atheromatous debris before it embolizes (that is, before balloon angioplasty and stenting), whereas intercoronary abciximab, with a potent antiplatelet agent, is hypothesized to work by leading to a much, much higher concentration of abciximab right at the site of the thrombus than if it is given by the normal intravenous route. The concentration can be 1,000x as high in the coronary artery as intravenously, and that can directly cause disaggregation of platelets. Since the early thrombus is very platelet-rich, intracoronary abciximab may lead to less macroscopic or large embolic debris.
In the past, studies that have been done to look at these two methods have yielded conflicting results as to whether they improve microcirculatory function, reduce infarct size and improve clinical outcomes. Therefore, we undertook what was probably to date the most carefully controlled, specific trial to see if using one or both of these devices could reduce infarct size. We took patients only with a large myocardial infarction, those with the greatest clinical need — specifically, patients with anterior myocardial infarction, with occlusion of the proximal or mid left anterior descending artery. These patients had to have presented early, within 3.5 to 4 hours after the onset of their infarct, so they would undergo their angioplasty while still in the time window for effective myocardial salvage. We know that if you wait too long for revascularization, beyond 4-6 hours or so, then, in general, the patient ends up with a transmural infarct and very little chance of myocardial salvage.