Purpose: Several studies have provided support for a pro-atherogenic role for remnant lipoproteins. Thus, the aim of this study was to compare remnant-like particle (RLP) cholesterol levels in patients with coronary artery disease who were normolipidemic with those in controls of similar age and gender. We also assessed the usefulness of measuring RLP-cholesterol levels in patients with type III dyslipidemia.Subjects and methods: Remnant-like particle cholesterol levels were measured in 63 normolipidemic men with coronary artery disease and 23 male controls of similar age as well as in 15 patients with type III dyslipidemia and 103 controls, using an immunoaffinity method.Results: Remnant-like particle cholesterol levels were significantly increased in men with coronary artery disease compared with controls (7.6 ± 3.8 mg/dL versus 5.7 ± 1.9 mg/dL, P <0.01). In patients with coronary artery disease, RLP-cholesterol levels were correlated with total triglyceride and non–high-density-lipoprotein (HDL) cholesterol levels, but not with HDL-cholesterol levels. RLP-cholesterol levels were significantly elevated in patients with type III dyslipidemia (median 119, range 31 to 240 mg/dL) compared with controls (median 5.6, range 2.2 to 10.5 mg/dL, P <0.001).Conclusion: Normolipidemic men with coronary artery disease have increased levels of RLP-cholesterol that is not detected with conventional lipid screening. The RLP-cholesterol assay is a simple method for detecting high concentrations of remnant lipoproteins in patients with type III dyslipidemia.

Purpose: A high placebo rate has been observed in previous IBD trials. Some have suggested that patients with mild baseline disease activity may increase the background “noise” and negatively impact the efficacy data. Positive data from two alicaforsen Phase 2 studies were recently presented, one placebo controlled and one with an active control, mesalamine (CS22). In the placebo controlled study (CS27), 112 subjects were randomized to compare 4 alicaforsen dose/schedules compared with placebo. Consistent with the CS22 results, CS27 study showed that 6 wks of 240mg alicaforsen qhs enema resulted in a durable clinical response that was statistically significant from placebo at Wks 18 and 30, (p = 0.04 and 0.03). To optimize the probability of success in Phase 3, we must understand the impact mild UC patients have on the efficacy data. Methods: Data from 44 subjects in the highest alicaforsen dose and placebo groups were reanalyzed to include only the subjects with moderate disease (DAI ≥ 7). Results: Eleven subjects met the criteria for moderate disease. Fig. A shows the high placebo response phenomenon commonly described in UC trials. Although the study demonstrated statistical difference at Wks 18 and 30, the study did not demonstrate a statistical difference at Wks 6 and 10 (p = 0.17 and 0.26). However, the placebo response was virtually eliminated when only patients with moderate disease were analyzed (Fig. B), without affecting the response curve of alicaforsen. Statistical difference was demonstrated at Wks 6 and 10 (both p = 0.05), even with a small number of patients. Conclusions: The sub-analysis confirms previous trial experience that inclusion of patients with mild baseline UC may significantly impact the placebo response rate and therefore has the potential to impact the outcome of the study. Careful consideration should be given in future studies to exclude patients with mild baseline disease activity. [figure 1]Figure