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

Michel Farnier, Erluo Chen, Amy O Johnson-Levonas, Christine McCrary Sisk, Yale B Mitchel, Michel Farnier, Erluo Chen, Amy O Johnson-Levonas, Christine McCrary Sisk, Yale B Mitchel

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.

Figures

Figure 1
Figure 1
Percentage change from baseline in LDL-C, non-HDL-C, and apoB in the overall treatment groups and defined by baseline TG 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
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
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.

References

    1. National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report. Circulation. 2002;106:3143–3421.
    1. Stone NJ, Robinson J, Lichtenstein AH, et al. ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults: a report of the American College of Cardiology/American Heart Association Task Force on practice guidelines. J Am Coll Cardiol. 2013 2013 Nov 7; Epub.
    1. Brunzell JD, Davidson M, Furberg CD, et al. Lipoprotein management in patients with cardiometabolic risk: consensus statement from the American Diabetes Association and the American College of Cardiology Foundation. Diabetes Care. 2008;31:811–822.
    1. Davidson MH, Ballantyne CM, Jacobson TA, et al. Clinical utility of inflammatory markers and advanced lipoprotein testing: advice from an expert panel of lipid specialists. J Clin Lipidol. 2011;5:338–367.
    1. Genest J, McPherson R, Frohlich J, et al. 2009 Canadian Cardiovascular Society/Canadian guidelines for the diagnosis and treatment of dyslipidemia and prevention of cardiovascular disease in the adult – 2009 recommendations. Can J Cardiol. 2009;25:567–579.
    1. Catapano AL, Reiner Ž, De Backer G, et al. ESC/EAS guidelines for the management of dyslipidaemias: the task force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS) Atherosclerosis. 2011;217:1–44.
    1. Boekholdt SM, Arsenault BJ, Mora S, et al. Association of LDL cholesterol, non-HDL cholesterol, and apolipoprotein B levels with risk of cardiovascular events among patients treated with statins: a meta-analysis. JAMA. 2012;307:1302–1309.
    1. Ingelsson E, Schaefer EJ, Contois JH, et al. Clinical utility of different lipid measures for prediction of coronary heart disease in men and women. JAMA. 2007;298:776–785.
    1. Liu J, Sempos CT, Donahue RP, Dorn J, Trevisan M, Grundy SM. Non-high-density lipoprotein and very-low-density lipoprotein cholesterol and their risk predictive values in coronary heart disease. Am J Cardiol. 2006;98:1363–1368.
    1. Pischon T, Girman CJ, Sacks FM, Rifai N, Stampfer MJ, Rimm EB. Non-high-density lipoprotein cholesterol and apolipoprotein B in the prediction of coronary heart disease in men. Circulation. 2005;112:3375–3383.
    1. Robinson JG, Wang S, Smith BJ, Jacobson TA. Meta-analysis of the relationship between non-high-density lipoprotein cholesterol reduction and coronary heart disease risk. J Am Coll Cardiol. 2009;53:316–322.
    1. Sniderman AD, Williams K, Contois JH, et al. A meta-analysis of low-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol, and apolipoprotein B as markers of cardiovascular risk. Circ Cardiovasc Qual Outcomes. 2011;4:337–345.
    1. Davidson MH. Reducing residual risk for patients on statin therapy: the potential role of combination therapy. Am J Cardiol. 2005;96:3K–13K.
    1. Guyton JR, Goldberg AC, Kreisberg RA, Sprecher DL, Superko R, O’Connor CM. Effectiveness of once-nightly dosing of extended-release niacin alone and in combination for hypercholesterolemia. Am J Cardiol. 1998;82:737–743.
    1. The Coronary Drug Project Research Group Clofibrate and niacin in coronary heart disease. JAMA. 1975;231:360–381.
    1. Brown BG, Zhao X-Q, Chait A, et al. Simvastatin and niacin, antioxidant vitamins, or the combination for the prevention of coronary disease. N Engl J Med. 2001;345:1583–1592.
    1. Taylor AJ, Sullenberger LE, Lee HJ, Lee JK, Grace KA. Arterial biology for the investigation of the treatment effects of reducing cholesterol (ARBITER) 2. A double-blind, placebo-controlled study of extended-release niacin on atherosclerosis progression in secondary prevention patients treated with statins. Circulation. 2004;110:3512–3517.
    1. The AIM-HIGH Investigators Niacin in patients with low HDL cholesterol levels receiving intensive statin therapy. N Engl J Med. 2011;365:2255–2267.
    1. HPS2-THRIVE Collaborative Group HPS2-THRIVE randomized placebo-controlled trial in 25 673 high-risk patients of ER niacin/laropiprant: trial design, pre-specified muscle and liver outcomes, and reasons for stopping study treatment. Eur Heart J. 2013;34:1279–1291.
    1. Ballantyne CM, Andrews TC, Hsia JA, Kramer JH, Shear C. Correlation of non-high-density lipoprotein cholesterol with apolipoprotein B: effect of 5 hydroxymethylglutaryl coenzyme A reductase inhibitors on non-high-density lipoprotein cholesterol levels. Am J Cardiol. 2001;88:265–269.
    1. Ballantyne CM, Raichlen JS, Cain VA. Statin therapy alters the relationship between apolipoprotein B and low-density lipoprotein cholesterol and non-high-density lipoprotein cholesterol targets in high-risk patients: the MERCURY II (Measuring Effective Reductions in Cholesterol Using Rosuvastatin) trial. J Am Coll Cardiol. 2008;52:626–632.
    1. Charlton-Menys V, Betteridge DJ, Colhoun H, et al. Targets of statin therapy: LDL cholesterol, non-HDL cholesterol, and apolipoprotein B in type 2 diabetes in the Collaborative Atorvastatin Diabetes Study (CARDS) Clin Chem. 2009;55:473–480.
    1. Idris I, Tate H, Ahmad A, McCormack T. Concordance between plasma apolipoprotein B levels and cholesterol indices among patients receiving statins and nonstatin treatment: post-hoc analyses from the UK InPractice study. J Clin Lipidol. 2011;5:316–323.
    1. Grundy SM, Vega GL, Tomassini JE, Tershakovec AM. Correlation of non-high-density lipoprotein cholesterol and low-density lipoprotein cholesterol with apolipoprotein B during simvastatin + fenofibrate therapy in patients with combined hyperlipidemia (a subanalysis of the SAFARI trial) Am J Cardiol. 2009;104:548–553.
    1. Farnier M, Taggart W, Dong Q, Lin J, Shah A, Brudi P. Influence of simvastatin, fenofibrate and/or ezetimibe on correlation of LDL and non-HDL cholesterol with apolipoprotein B in mixed dyslipidemic patients. J Clin Lipidol. 2011;5:179–187.
    1. Farnier M, Guyton JR, Jensen E, Polis AB, Johnson-Levonas AO, Brudi P. Effects of Ezetimibe, simvastatin and ezetimibe/simvastatin on correlations between apolipoprotein B, LDL cholesterol and non HDL cholesterol in patients with primary hypercholesterolemia. Atherosclerosis. 2013;229:415–422.
    1. Gleim G, Ballantyne CM, Liu N, et al. Efficacy and safety profile of co-administered ER niacin/laropiprant and simvastatin in dyslipidaemia. Br J Cardiol. 2009;16:90–97.
    1. Friedewald WT, Levy RI, Fredrickson DS. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem. 1972;18:499–502.
    1. Maccubbin D, Bays HE, Olsson AG, et al. Lipid-modifying efficacy and tolerability of extended release niacin/laropiprant in patients with primary hypercholesterolaemia or mixed dyslipidaemia. Int J Clin Pract. 2008;62:1959–1970.

Source: PubMed

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