Background

In addition to low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (non–HDL-C), apolipoprotein B (ApoB), and high-sensitivity C-reactive protein (hs-CRP) are considered predictive for cardiovascular disease in type 2 diabetes mellitus (T2DM) patients.

Objective

To assess the proportion of T2DM patients with hypercholesterolemia who attained the optional target level of LDL-C (<70 mg/dL) and additionally non-HDL-C (<100 mg/dL), ApoB (<90 mg/dL), and hs-CRP (<2 mg/L), following treatment with ezetimibe/simvastatin (E/S) vs atorvastatin (A).

Methods

This post-hoc analysis of a multicenter, randomized, double-blind, 6-week parallel study assessed the proportion of T2DM patients who attained specified LDL-C levels and non-HDL-C, ApoB, and hs-CRP with usual, recommended starting doses of E/S (10/20 mg) vs A (10 or 20 mg) and next highest doses of E/S (10/40 mg) vs A (40 mg) by logistic regression. Baseline triglyceride and hs-CRP effects were also evaluated.

Results

Significantly higher percentages of patients treated with E/S compared to A achieved individual and concurrent target levels of LDL-C (<70 mg/dL), non-HDL-C (<100 mg/dL), and ApoB (<90 mg/dL) at all dose comparisons (P < 0.05 to P < 0.001). Baseline triglyceride levels had no effect on reaching LDL-C levels. Attainment of non-HDL-C (<100 mg/dL), and ApoB (<90 mg/dL) was lower at triglycerides ≥200 mg/dL than <200 mg/dL. Achievement of hs-CRP level (<2 mg/L) was comparable for both treatments. Significantly more patients attained both LDL-C (<70 mg/dL) and hs-CRP (<2 mg/L) at all E/S doses compared to A (P < 0.05 to P < 0.001), regardless of baseline CRP levels.

Conclusion

E/S provides a therapeutic option to T2DM patients for lowering not only LDL-C, but also non-HDL-C, ApoB, and hs-CRP. These factors may help guide assessment and treatment of cardiovascular disease risk in these patients.

Objective

Patients with metabolic syndrome (MetS) are at increased risk for cardiovascular disease. Niacin improves lipid abnormalities associated with MetS, but is underused, mainly because of flushing. Laropiprant (LRPT) reduces niacin-induced flushing and, in combination with extended-release niacin (ERN/LRPT), improves lipid levels.

Methods

In this post-hoc subgroup analysis of a phase 3 randomized, double-blind, placebo-controlled, 24-week study (n = 1613), we evaluated the efficacy and safety of ERN/LRPT in dyslipidemic patients with MetS. Dyslipidemic patients were randomized 3:2:1 to ERN/LRPT 1 g, ERN 1 g, or placebo. After 4 weeks, active treatment doses were doubled (2 tablets) for 20 weeks.

Results

Relative to placebo, ERN/LRPT significantly lowered low-density lipoprotein cholesterol and increased high-density lipoprotein cholesterol levels to a similar degree in MetS and non-MetS cohorts. ERN/LRPT significantly (P < .001) lowered triglyceride levels versus placebo in patients with MetS and without MetS (−30.2% vs −22.2%, respectively). The between subgroup difference in triglyceride lowering was not significant. For all lipid parameters, ERN/LRPT and ERN produced similar magnitude changes. ERN/LRPT and ERN produced similar increases in median fasting blood glucose levels versus placebo in patients with MetS (2.0 and 4.0 mg/dL, respectively) and without MetS (4.0 mg/dL for both groups), consistent with a known effect of niacin.

Conclusion

In patients with MetS, ERN/LRPT improves multiple lipid parameters associated with increased cardiovascular disease risk. ERN/LRPT numerically improved triglyceride levels more in patients with versus without MetS, which is likely related to greater baseline triglycerides in MetS patients.

Objectives

Correlations between low-density lipoprotein cholesterol (LDL-C), or nonhigh-density lipoprotein cholesterol (non-HDL-C) and apolipoprotein B (Apo B) change after statin therapy has been initiated in hypercholesterolemic patients. This post-hoc analysis studied the correlation between these parameters in patients with mixed dyslipidemia before and after receiving lipid-lowering treatment.

Results

Data from two randomized, double-blind studies of 1112 patients with mixed dyslipidemia receiving treatment (ezetimibe 10 mg, ezetimibe/simvastatin 10/20 mg, fenofibrate 160 mg, ezetimibe + fenofibrate 10/160 mg, or ezetimibe/simvastatin + fenofibrate 10/20/160 mg) were pooled. Correlation analyses and simple linear regression analyses were performed at baseline in untreated patients and after 12 weeks of treatment in the whole pooled population, the treatment groups, and after stratification by baseline triglyceride levels (150-250, ≥250 mg/dL) within the treatment groups. Both LDL-C and non-HDL-C were closely correlated with levels of Apo B at baseline, and these correlations improved after treatment. When using the fitted simple linear regression equations, we found that the on-treatment LDL-C and non-HDL-C levels corresponding to an Apo B of 90, 80, and 70 mg/dL were lower than proposed LDL-C and non-HDL-C treatment targets. For TG ≥250 mg/dL, the corresponding LDL-C was generally lower than that for triglycerides 150-250 mg/dL, except in the cases with fenofibrate in the treatment.

Conclusion

The results of these analyses suggest that achieving goal-specified levels of Apo B in statin-treated patients with mixed dyslipidemia would require more aggressive LDL-C lowering to achieve the greatest reduction in LDL particle number.

Background

Metabolic syndrome (MetS) and atherosclerotic vascular disease (AVD) are associated with increased coronary heart disease risk.

Objective

To assess percent change from baseline in lipids and high-sensitivity C-reactive protein (hs-CRP) levels and the proportion of subjects reaching specified low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (HDL-C) and apolipoprotein B (Apo B) single, dual, and triple targets and hs-CRP <2 mg/L among subjects with and without AVD treated with ezetimibe/simvastatin or atorvastatin for 6 weeks.

Methods

Adults (N = 1143) with MetS and hypercholesterolemia were randomized to starting and next higher doses of ezetimibe/simvastatin (10/20 or 10/40 mg) or atorvastatin (10, 20, or 40 mg).

Results

Ezetimibe/simvastatin produced significantly greater reductions in evaluated lipids than atorvastatin for most prespecified dose comparisons. More subjects without AVD achieved LDL-C levels <100 mg/dL, non-HDL-C levels <130 mg/dL, and dual LDL-C/non-HDL targets (83%-92% vs 62%-76%) and Apo B <90 mg/dL or triple targets (65%-75% vs 41%-49%) with 40 mg of atorvastatin or 10/20-40 mg of ezetimibe/simvastatin compared with 10 or 20 mg of atorvastatin, respectively. More subjects with AVD achieved LDL-C<70 mg/dL and non-HDL-C<100 mg/dL single and dual targets (65%-80%) and Apo B <80 mg/dL (53%-63%) with 10/20-40 mg of ezetimibe/simvastatin than with 40 mg of atorvastatin (40%-49%). More subjects achieved triple lipid targets with 10/20-40 mg of ezetimibe/simvastatin versus 10–40 mg of atorvastatin (50%-63% vs 24%-40%). Achievement of hs-CRP <2 mg/L was similar across all doses regardless of AVD status.

Conclusions

More intensive therapy was required for >80% of subjects to achieve LDL-C <100 mg/dL and non-HDL-C <130 mg/dL and for the majority of subjects to achieve lower levels of LDL-C <70 mg/dL, non-HDL-C <100 mg/dL, and/or Apo B <90 mg/dL. The effect of ezetimibe on cardiovascular risk reduction has yet to be established. (Clintrials.gov no: NCT00409773)