Effects of extended-release niacin/laropiprant, simvastatin, and the combination on correlations between apolipoprotein B, LDL cholesterol, and non-HDL cholesterol in patients with dyslipidemia

Abstract

Background: Statins modify correlations between apolipoprotein B (apoB) and low-density lipoprotein cholesterol (LDL-C) and apoB and non-high-density lipoprotein cholesterol (non-HDL-C); however, it is not known whether niacin-based therapies have similar effects.

Objective: To evaluate the effects of extended-release niacin (ERN)/laropiprant (LRPT), simvastatin (SIMVA), and ERN/LRPT + SIMVA (pooled ERN/LRPT + SIMVA) on apoB:LDL-C and apoB:non-HDL-C correlations in dyslipidemic patients.

Methods: This post-hoc analysis of a 12-week study evaluated the apoB:LDL-C and apoB:non-HDL-C correlations in dyslipidemic patients randomized equally to double-blind ERN/LRPT 1 g/20 mg, SIMVA 10, 20, or 40 mg, or ERN/LRPT 1 g/20 mg + SIMVA (10, 20, or 40 mg) once daily for 4 weeks. At week 5, doses were doubled in all groups except SIMVA 40 mg (unchanged) and ERN/LRPT 1 g/20 mg + SIMVA 40 mg (switched to ERN/LRPT 2 g/40 mg + SIMVA 40 mg). Simple linear regression analyses were used to calculate LDL-C and non-HDL-C levels corresponding to known apoB baseline values (ie, in untreated patients) and following treatment.

Results: The apoB:LDL-C and apoB:non-HDL-C correlations were higher and the predicted LDL-C and non-HDL-C levels for a known apoB value were considerably lower following treatment with ERN/LRPT, SIMVA and ERN/LRPT + SIMVA compared with untreated patients at baseline.

Conclusion: Greater dissociation of apoB, LDL-C, and non-HDL-C targets occur following treatment with ERN/LRPT, SIMVA, and ERN/LRPT + SIMVA in patients with dyslipidemia. The achievement of more aggressive LDL-C and non-HDL-C goals in patients receiving lipid-modifying therapy may further reduce coronary risk by normalizing apoB-containing atherogenic lipoproteins.

Trial registration: ClinicalTrials.gov NCT00269217.

Keywords: LDL-C; apoB; non-HDL-C.

Figure 1

Percentage change from baseline in LDL-C, non-HDL-C, and apoB in the overall treatment groups and defined by baseline TG <2.26 and ≥2.26 mmol/L. Abbreviations: apoB, apolipoprotein B; CI, confidence interval; ERN, extended-release niacin; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; LRPT, laropiprant; LS, least squares; SIMVA, simvastatin; TG, triglyceride.

Figure 2

Scatterplots of apoB versus LDL-C at baseline (A) and following treatment with ERN/LRPT, pooled SIMVA, or pooled ERN/LRPT + SIMVA (B). The upper thresholds for the less-stringent LDL-C <2.59 mmol/L and apoB <0.9 g/L goals are denoted by horizontal and vertical lines, respectively. Right lower quadrant in Figure 2B shows the subjects who met LDL-C goal <2.59 mmol/L but did not reach apoB goal <0.9 g/L after treatment. Abbreviations: apoB, apolipoprotein B; ERN, extended-release niacin; LDL-C, low-density lipoprotein cholesterol; LRPT, laropiprant; SIMVA, simvastatin.

Figure 3

Scatterplots of apoB versus non-HDL-C at baseline (A) and following treatment with ERN/LRPT, pooled SIMVA, or pooled ERN/LRPT + SIMVA (B). The upper thresholds for the less-stringent non-HDL-C <3.36 mmol/L and apoB <0.9 g/L goals are denoted by horizontal and vertical lines, respectively. Right lower quadrant in Figure 3B shows the subjects who met non-HDL-C goal <3.36 mmol/L but did not reach apoB goal <0.9 g/L after treatment. Abbreviations: apoB, apolipoprotein B; ERN, extended-release niacin; HDL-C, high-density lipoprotein cholesterol; LRPT, laropiprant; SIMVA, simvastatin.