Abstract 684: Changes in Levels of High Density Lipoprotein Cholesterol Predict the Impact of Torcetrapib on Progression of Coronary Atherosclerosis: Insights from ILLUSTRATE
Background: Administration of the CETP inhibitor torcetrapib does not slow the rate of progression of coronary atherosclerosis. The reason for the lack of therapeutic efficacy remains unknown. This analysis investigated the relationship between changes in HDL cholesterol (HDL-C) and LDL cholesterol (LDL-C) and atheroma volume in patients treated with torcetrapib.
Methods: 910 patients with angiographic coronary artery disease underwent IVUS imaging within a single coronary artery before and during 24 months of treatment with torcetrapib (n = 464) or placebo (n = 446) on a background of atorvastatin therapy. The relationship between changes in levels of HDL-C and LDL-C and both percent atheroma volume (PAV) and total atheroma volume (TAV) was evaluated in patients treated with torcetrapib.
Results: Administration of torcetrapib raised HDL-C by 61% and lowered LDL-C by 20% when compared to atorvastatin alone. An inverse relationship was observed between changes in HDL-C and both PAV (r = −0.17, p < 0.001) and TAV (r = −0.17, p < 0.001). Patients with the highest level of HDL-C (> 87 mg/dL) had the lowest rate of progression of PAV (−0.7 v +0.7%, p = 0.0003) and TAV (−9.2 v −4.6 mm3, p = 0.09). The greatest elevation in level of HDL-C (> 80%) was associated with the lowest progression of PAV (−0.3 v +0.9%, p = 0.002) and TAV (−12.6 v −3.4 mm3, p = 0.0006). Patients undergoing regression (any reduction in PAV) had greater absolute levels (73 v 66 mg/dL, p = 0.02) and changes (59.5 v 48.3%, p = 0.02) of HDL-C. No difference in the impact of torcetrapib on changes in PAV (+0.3 v +0.1%, p = 0.34) and TAV (−9.1 v −9.3 mm3, p = 0.95) was observed in patients with baseline levels below or above 40 mg/dL. No relationship was observed between changes in LDL-C and either PAV (r = 0.06, p = 0.20) or TAV (r = 0.07, p = 0.12) in torcetrapib treated patients. On multivariate analysis, changes in levels of HDL-C independently predicted the impact of torcetrapib on progression of PAV (p = 0.007) and TAV (p = 0.004).
Conclusion: Increasing levels of HDL-C from torcetrapib treatment were associated with a beneficial impact of torcetrapib on plaque progression. This is consistent with the generation of functional HDL particles and suggests other effects to be responsible for the lack of benefit of torcetrapib.