Response to Letters Regarding Article, “Effect of Rosuvastatin Therapy on Coronary Artery Stenoses Assessed by Quantitative Coronary Angiography: A Study to Evaluate the Effect of Rosuvastatin on Intravascular Ultrasound–Derived Coronary Atheroma Burden”
Authors: Christie M. Ballantyne, Joel S. Raichlen, Valerie A. Cain, Stephen J. Nicholls, Steven E. Nissen, Raimund Erbel, Jean-Claude Tardif, Sorin J. Brener
Journal: Circulation (2008)

for their interest and commentaries on our analysis. 1In response to Dr Kaneda's request for sensitivity analyses, we applied the same conservative assumptions employed in the intravascular ultrasound (IVUS) analysis 2 to all noncompleters and to those with ischemic events and found that statistically significant regression occurred in both percentage diameter stenosis (%DS) and minimum lumen diameter.With regard to the assessment of disease progression, as in previous quantitative coronary angiography (QCA) studies that we referenced, 3 the prespecified outcome variable was the change in baseline stenoses Ͼ25%.This is very reasonable because some studies have shown that only progression of stenoses present at baseline was predictive of coronary events. 4In A Study to Evaluate the Effect of Rosuvastatin on Intravascular Ultrasound-Derived Coronary Atheroma Burden (ASTEROID), 379 of the 507 randomized patients (75%) had both a baseline and a follow-up QCA study.Sixteen of these patients (4.2%) developed a new lesion of Ͼ25% stenosis that represented an increase of at least 20% from baseline.Of those 379 patients, the 292 (77%) with baseline stenoses Ͼ25% made up the QCA study population, and 12 (4.1%) of these 292 patients developed a new lesion.We agree that it would be of interest for a meta-analysis to combine the actual patient values from multiple trials, because individual statin studies are not large enough to correlate on-therapy low-density lipoprotein cholesterol (LDL-C) levels with changes in imaging surrogate markers.We examined the values in this study and found the same trend that we reported for on-therapy LDL-C to be present for the percentage change in LDL-C (ie, the quartile with the greatest percentage lowering of LDL-C had more benefit in %DS and minimum lumen diameter than those with the lowest quartile of LDL-C lowering).On the topic of differences between IVUS and QCA imaging, investigators were instructed to select 1 target artery for IVUS that was free of significant luminal narrowing (prespecified with no lesion Ն50%).The subsegment with greatest disease by IVUS was defined as the region with the most atheroma in the wall; it was independent of the angiogram.Thus, IVUS and QCA focused on different segments of the coronary arteries.The QCA segments were not aligned with IVUS data, preventing direct comparison in this study.With regard to the comments by Drs Sutton, Blumenthal, and Kapur, the prior IVUS analysis from ASTEROID focused on progression and regression of atheroma in coronary arteries that were free of significant stenoses.The current QCA analysis focused on coronary segments with baseline stenoses and showed small but significant regression of %DS and minimum lumen diameter.This contrasts with the monotherapy studies in our figures that showed progression that was significantly less than that of the natural history of atherosclerosis demonstrated in their placebo arms.Relative to the calculation of %DS, the reference lumen diameter appeared stable during the study: 2.62 (0.60) mm [mean (SD)] at baseline and 2.62 (0.59) mm at end of study.The changes in %DS and minimum lumen diameter thus correlated closely with each other (rϭ0.97,PϽ0.0001).With regard to the cross-sectional area, as noted above, the QCA and IVUS studies focused on different regions of the coronary arteries.Thus, no direct comparisons were made between segment diameters imaged by QCA and lumen volumes determined by IVUS.No data on QCA were presented in the apolipoprotein A-I Milano article.We agree that the relationship between changes in atheroma volume and luminal dimensions merits additional analysis to better understand remodeling.To examine this, we are performing additional analyses of the ASTEROID IVUS data.