Long-term safety and efficacy of a once-daily niacin/lovastatin formulation for patients with dyslipidemia*☆,
Section snippets
Study design:
This study was designed to meet published regulatory guidelines5 for the minimum extent of exposure to oral lipid-modifying agents. These guidelines specify a minimum exposure of ≥600 patients treated for 6 months and 200 patients treated for 12 months. Thus, a target patient population of 800 was selected, taking into account the possibility of patient attrition over time. The interim findings reported here are based on a data lock date declared when >600 patients had been followed for 6
Results
Of 818 eligible patients who were enrolled sequentially in the study, 4 failed to take any study medication. Thus, 814 patients were evaluable for safety and efficacy determinations.
Discussion
Once-daily niacin-ER/lovastatin was highly effective and generally well tolerated in this large, multicenter, open-label phase 3 trial. Based on the efficacy data, this drug combination seems to confer greater improvements on the overall lipoprotein profile than either agent alone.
An additive effect of these 2 drugs used in combination is consistent with current concepts of their different and complementary mechanisms of action.7, 8 Niacin primarily inhibits hepatic triglyceride synthesis,
References (27)
- et al.
Contrasting effects of unmodified and time-release forms of niacin on lipoprotein in hyperlipidemic subjectsclues to mechanism of action of niacin
Metabolism
(1985) - et al.
Effectiveness of once-nightly dosing of extended-release niacin alone and in combination for hypercholesterolemia
Am J Cardiol
(1998) - et al.
Regulatory concerns at various phases of drug development
Am J Cardiol
(1998) - et al.
Equivalent efficacy of a time-release form of niacin (Niaspan) given once-a-night versus plain niacin in the management of hyperlipidemia
Metabolism
(1998) - et al.
Multiple-dose efficacy and safety of an extended-release form of niacin in the management of hyperlipidemia
Am J Cardiol
(2000) - et al.
Treatment of hyperlipidemia with combined niacin-statin regimens
Am J Cardiol
(1998) - et al.
The benefits of niacin in atherosclerosis
Curr Atheroscler Rep
(2001) - et al.
A comparison of the efficacy and toxic effects of sustained- vs immediate-release niacin in hypercholesterolemic patients
JAMA
(1994) Summary of the second report of the National Cholesterol Education Program (NCEP) expert panel on the detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel II)
JAMA
(1993)- et al.
Niacin accelerates intracellular apo B degradation by inhibiting triacylglycerol synthesis in human hepatoblastoma (Hep G2) cells
Arterioscler Thromb Vasc Biol
(1999)
Niacin decreases removal of high-density lipoprotein apolipoprotein A-I but not cholesterol ester by Hep G2 cells. Implication for reverse cholesterol transport
Arterioscler Thromb Vasc Biol
Mechanism of action of niacin on lipoprotein metabolism
Curr Atheroscler Rep
Statin-induced inhibition of the Rho-signaling pathway actives PPAR α and induces HDL apoA-I
J Clin Invest
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This study was supported by Kos Pharmaceuticals, Miami, Florida.