Response to Letter Regarding Article, “Intracoronary Compared With Intravenous Bolus Abciximab Application in Patients With ST-Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention”
We agree with Abdellaoui et al that the area at risk may explain up to 50% of infarct size, as this has been shown in experimental trials. In our randomized trial of intracoronary versus intravenous abciximab bolus administration, we did not assess the area at risk, which might be a limitation.1 However, because this was a randomized trial, differences in area at risk are extremely unlikely given that all other baseline characteristics were well balanced between the 2 randomized groups. Furthermore, the sum of ST-segment elevation at baseline (before percutaneous coronary intervention) and the number of elevated leads were similar between the treatment groups, which indicates the same area at risk. ST-segment evaluation might have a similar value for assessment of the area at risk as the somewhat more inaccurate left ventricular angiography.2,3 As stated in our discussion, magnetic resonance is now able to assess the area at risk retrospectively from T2-weighted images (edema imaging).4 We acquired 3 short-axis slices for the assessment of edema in which no difference in the amount of edema (or area at risk) was seen, which confirms that no differences were present in the area at risk.
The authors of the letter published much smaller trials using enzyme release (as an indirect marker of infarct size) as the primary end point,2 which has much larger variability than any other imaging method.5 This was a major reason to use enzyme release only as a secondary end point in our Randomized Leipzig Immediate Percutaneous Coronary Intervention Abciximab IV Versus IC in ST-Elevation Myocardial Infarction (LIPSIAbciximab) trial.1
Testing for predictive factors plays a major role in small and borderline-powered trials. We tested major predictive factors with the course of abciximab administration in a multiple regression analysis. However, even after adjustment for baseline characteristics, intracoronary abciximab bolus administration still led to statistically significant results for infarct size and microvascular obstruction reduction. Currently, we have begun a large multicenter trial of nearly 2000 patients to assess the benefits of intracoronary abciximab bolus administration that will clearly elucidate the clinical impact of this administration route.
Thiele H, Schindler K, Friedenberger J, Eitel I, Fürnau G, Grebe E, Erbs S, Linke A, Möbius-Winkler S, Kivelitz D, Schuler G. Intracoronary compared with intravenous bolus abciximab application in patients with ST-elevation myocardial infarction undergoing primary percutaneous coronary intervention: the Randomized Leipzig Immediate Percutaneous Coronary Intervention Abciximab IV Versus IC in ST-Elevation Myocardial Infarction Trial. Circulation. 2008; 118: 49–72.
Piot C, Croisille P, Staat P, Thibault H, Rioufol G, Mewton N, Elbelghiti R, Cung TT, Bonnefoy E, Angoulvant D, Macia C, Raczka F, Sportouch C, Gahide G, Finet G, Andre-Fouet X, Revel D, Kirkorian G, Monassier J-P, Derumeaux G, Ovize M. Effect of cyclosporine on reperfusion injury in acute myocardial infarction. N Engl J Med. 2008; 359: 473–481.
Schroder R. Prognostic impact of early ST-segment resolution in acute ST-elevation myocardial infarction. Circulation. 2004; 110: e506–e510.
Aletras AH, Tilak GS, Natanzon A, Hsu L-Y, Gonzalez FM, Hoyt RF Jr, Arai AE. Retrospective determination of the area at risk for reperfused acute myocardial infarction with T2-weighted cardiac magnetic resonance imaging: histopathological and Displacement Encoding with Stimulated Echoes (DENSE) functional validations. Circulation. 2006; 113: 1865–1870.