Cath Lab Digest

INFUSE-AMI screened more than 3,600 patients, at 37 sites in 6 countries around the world, and we only enrolled patients with anterior myocardial infarction, proximal or mid left anterior descending coronary artery occlusion, 3.5 to 4 hours within their infarct time, no prior myocardial infarction and some other contraindications, to enroll a total of 452 patients. We randomized them in a 2 x 2 factorial design, to either aspiration, yes vs. no, and each of those groups was sub-randomized to intracoronary abciximab, yes vs. no. All patients were treated with bivalirudin as the foundation anticoagulant. In the intracoronary abciximab arm, since no patient received a 12-hour infusion of abciximab, patients were treated only with a bolus of intracoronary abciximab versus no intracoronary abciximab, allowing us to isolate its effects. Finally, the primary endpoint was infarct size measured by cardiac magnetic resonance imaging (cardiac MRI) at 30 days. A unique aspect of the trial was the choice of a 30-day endpoint. Most studies would have a cardiac MRI endpoint at 2 to 4 days, but that leads to a much larger infarct size, because cardiac MRI at 2 to 7 days misclassifies myocardial edema as infarct. There is a great deal of edema early on which resolves over the first 30 days in particular, but then even ongoing probably for the entire year. By waiting to 30 days, we hoped to gain a more accurate impression of infarct size by having probably a 60-70% resolution of myocardial edema.

The primary endpoint of cardiac MRI at 30 days showed intracoronary abciximab “significantly but modestly” reduced the infarct size.

We hypothesized at the beginning and powered the trial for an infarct size of approximately 24% of the left ventricle. So 24% of the entire 100% of the left ventricle would be involved with an infarct in the control group, and we thought it would be clinically relevant if we could reduce that by a relative 25% or an absolute 6% down to an infarct size of 18%. Since we did the study with an endpoint at 30 days instead of earlier, the infarcts were slightly smaller than anticipated in the control group, at about 17.9% of the left ventricle, which is still a very large infarct. We reduced it to 15.1% with intracoronary abciximab, which is approximately a 3% reduction of myocardial size. That is about half the size that we had pre-specified would be clinically relevant. It was a real reduction, it was statistically significant, but the real question is, what would a 3% reduction in infarct size mean to a single patient or 1,000 patients? That can only be answered in a large-scale, randomized trial. The current trial was underpowered for clinical events. We never expected to see differences in clinical events, nor did we, and while we did not see any statistically significant harm from abciximab, which would primarily be bleeding or thrombocytopenia, we would need a large-scale trial to see if the bolus-only would make a significant difference.

What did we learn about manual aspiration?

Well, it had a neutral effect. There was no effect, basically, on reducing infarct size or improving microcirculatory function with aspiration thrombectomy in this carefully controlled study.

What can clinicians take away from that for their daily practice?

If manual aspiration does not reduce infarct size, there is no valid mechanistic reason to believe that it would reduce mortality, reduce heart failure or otherwise improve clinical outcomes. However, these were the results in all comers who met the inclusion criteria, and we did not specify the amount of thrombus that had to be present. We have not yet performed an analysis based on how much thrombus was present, but will do so in the future. I still think that aspiration thrombectomy, from a practical point of view, has a role for patients with a very large amount of thrombus in the coronary artery. From experience, we know the results will not be satisfactory if you only directly balloon and stent in these patients. For most lesions that cause acute myocardial infarction, it does not appear that aspiration thrombectomy is at all beneficial. And of course, there is some cost associated with it.

The trial also showed a lack of significant decrease in abnormal wall motion in the intracoronary abciximab group.

The study was underpowered to show that and there was a strong trend toward reduction in abnormal wall motion with abciximab. P-value was .08. There was also a trend, but more non-significant, for about a 1.3% improvement in global left ventricular ejection fraction at 30 days. Again, if a larger study was performed, if we had randomized 800 patients instead of 452, it’s likely that both of those numbers would have been significant.

What about other secondary endpoints, such as ST-segment resolution and myocardial perfusion?

With both therapies, intracoronary abciximab and aspiration thrombectomy, other measures, such as angiographic myocardial blush, an angiographic surrogate of blood getting into the myocardium, and ST-segment resolution, which means, did we stop the ongoing injury, were both neutral. That was a little bit surprising, especially in the intracoronary abciximab arm, where we would have expected that to track along with the decreased infarct size at 30 days. We will be doing more studies to try to figure out why there was discordance in those outcome measures. But most people would ascribe infarct size to be the more powerful surrogate of clinical outcomes.

Any final thoughts?