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Safety and efficacy of laropiprant and extended-release niacin combination in the management of mixed dyslipidemias and primary hypercholesterolemia.

Viljoen A, Wierzbicki AS - Drug Healthc Patient Saf (2010)

Bottom Line: It was the first lipid-lowering drug to demonstrate a reduction in cardiovascular events, and remains the only one that has consistently shown benefits on surrogate outcomes when added to background therapies of other lipid-lowering drugs, including statins.Niacin's uptake in clinical practice has been less successful due to its side-effect profile, most notable being flushing.The uncovering of the mechanism by which flushing is induced, together with the development of a prostaglandin D(2) receptor inhibitor (laropiprant) which reduces this downstream flushing effect of niacin, has sparked new promise in therapeutic lipid management.

View Article: PubMed Central - PubMed

Affiliation: Lister Hospital, Stevenage, Hertfordshire, UK;

ABSTRACT
Statins form the cornerstone of pharmaceutical cardiovascular disease prevention. However, despite very effective statin intervention, the majority of events remain unpreventable. In some cases statin therapy alone is insufficient to achieve adequate lipid levels whereas other patients are unable to tolerate statins. This calls for additional treatment options. Niacin has a long history of success in reducing low-density lipoprotein cholesterol and triglycerides, and increasing high-density lipoprotein cholesterol. It was the first lipid-lowering drug to demonstrate a reduction in cardiovascular events, and remains the only one that has consistently shown benefits on surrogate outcomes when added to background therapies of other lipid-lowering drugs, including statins. Niacin's uptake in clinical practice has been less successful due to its side-effect profile, most notable being flushing. The uncovering of the mechanism by which flushing is induced, together with the development of a prostaglandin D(2) receptor inhibitor (laropiprant) which reduces this downstream flushing effect of niacin, has sparked new promise in therapeutic lipid management. It provides an additional treatment option into managing lipid abnormalities. The uptake in clinical practice of the niacin-laropiprant combination will depend on the relative improvements experienced by the patient in the side-effect profile compared to other treatment options, as well as on the the keenly-awaited outcome studies currently underway. Until these data become available guidelines and recommendations are unlikely to change and niacin's position in therapeutic cardiovascular risk prevention will be determined by clinician opinion and experience, and patient preferences.

No MeSH data available.


Related in: MedlinePlus

Schematic illustration of the mechanism by which niacin induces flushing.Abbreviation: PG, prostaglandin.
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f1-dhps-2-061: Schematic illustration of the mechanism by which niacin induces flushing.Abbreviation: PG, prostaglandin.

Mentions: Despite its having a better side-effect profile compared to the other forms of niacin, the discontinuation rate of the ER niacin still remains significant. The uncovering of the mechanism by which flushing is induced has sparked new promise into therapeutic lipid management.84,90 In general, flushing symptoms can occur following vasodilatation of small capillaries under the skin, a response that can be mediated via histamine/bradykinin or prostaglandins (PGs). This side-effect is not unique to niacin but is also seen with other drugs such as selective serotonin reuptake inhibitors.84 The flushing of niacin is not believed to be via histamine/bradykinin pathways, but rather via PGs. The G-protein-coupled receptor GRP109A, seen in adipocytes, also exists on dermal dendritic cells. Activation of the receptor on these cells induces the mobilization of arachidonic acid which leads to its conversion to, amongst other effects, the production of vasodilatory PGs, specifically forms D2 and E2. These PGs cause their effects by acting in particular through the DP1, EP2, and EP4 receptors.84,90 Figure 1 illustrates schematically the mechanism by which niacin induces flushing. Considering the advantageous effects of niacin, strategies to improve patient compliance by reducing flushing are important. This can be managed by various approaches namely: dose titration, patient education and additional pharmacological therapies.84 Nonsteroidal anti-inflammatory drugs are a logical treatment option as they are able to decrease the production of multiple prostaglandins by inhibiting cyclooxygenase and endoperoxidase (also referred to as COX).84,91


Safety and efficacy of laropiprant and extended-release niacin combination in the management of mixed dyslipidemias and primary hypercholesterolemia.

Viljoen A, Wierzbicki AS - Drug Healthc Patient Saf (2010)

Schematic illustration of the mechanism by which niacin induces flushing.Abbreviation: PG, prostaglandin.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3108693&req=5

f1-dhps-2-061: Schematic illustration of the mechanism by which niacin induces flushing.Abbreviation: PG, prostaglandin.
Mentions: Despite its having a better side-effect profile compared to the other forms of niacin, the discontinuation rate of the ER niacin still remains significant. The uncovering of the mechanism by which flushing is induced has sparked new promise into therapeutic lipid management.84,90 In general, flushing symptoms can occur following vasodilatation of small capillaries under the skin, a response that can be mediated via histamine/bradykinin or prostaglandins (PGs). This side-effect is not unique to niacin but is also seen with other drugs such as selective serotonin reuptake inhibitors.84 The flushing of niacin is not believed to be via histamine/bradykinin pathways, but rather via PGs. The G-protein-coupled receptor GRP109A, seen in adipocytes, also exists on dermal dendritic cells. Activation of the receptor on these cells induces the mobilization of arachidonic acid which leads to its conversion to, amongst other effects, the production of vasodilatory PGs, specifically forms D2 and E2. These PGs cause their effects by acting in particular through the DP1, EP2, and EP4 receptors.84,90 Figure 1 illustrates schematically the mechanism by which niacin induces flushing. Considering the advantageous effects of niacin, strategies to improve patient compliance by reducing flushing are important. This can be managed by various approaches namely: dose titration, patient education and additional pharmacological therapies.84 Nonsteroidal anti-inflammatory drugs are a logical treatment option as they are able to decrease the production of multiple prostaglandins by inhibiting cyclooxygenase and endoperoxidase (also referred to as COX).84,91

Bottom Line: It was the first lipid-lowering drug to demonstrate a reduction in cardiovascular events, and remains the only one that has consistently shown benefits on surrogate outcomes when added to background therapies of other lipid-lowering drugs, including statins.Niacin's uptake in clinical practice has been less successful due to its side-effect profile, most notable being flushing.The uncovering of the mechanism by which flushing is induced, together with the development of a prostaglandin D(2) receptor inhibitor (laropiprant) which reduces this downstream flushing effect of niacin, has sparked new promise in therapeutic lipid management.

View Article: PubMed Central - PubMed

Affiliation: Lister Hospital, Stevenage, Hertfordshire, UK;

ABSTRACT
Statins form the cornerstone of pharmaceutical cardiovascular disease prevention. However, despite very effective statin intervention, the majority of events remain unpreventable. In some cases statin therapy alone is insufficient to achieve adequate lipid levels whereas other patients are unable to tolerate statins. This calls for additional treatment options. Niacin has a long history of success in reducing low-density lipoprotein cholesterol and triglycerides, and increasing high-density lipoprotein cholesterol. It was the first lipid-lowering drug to demonstrate a reduction in cardiovascular events, and remains the only one that has consistently shown benefits on surrogate outcomes when added to background therapies of other lipid-lowering drugs, including statins. Niacin's uptake in clinical practice has been less successful due to its side-effect profile, most notable being flushing. The uncovering of the mechanism by which flushing is induced, together with the development of a prostaglandin D(2) receptor inhibitor (laropiprant) which reduces this downstream flushing effect of niacin, has sparked new promise in therapeutic lipid management. It provides an additional treatment option into managing lipid abnormalities. The uptake in clinical practice of the niacin-laropiprant combination will depend on the relative improvements experienced by the patient in the side-effect profile compared to other treatment options, as well as on the the keenly-awaited outcome studies currently underway. Until these data become available guidelines and recommendations are unlikely to change and niacin's position in therapeutic cardiovascular risk prevention will be determined by clinician opinion and experience, and patient preferences.

No MeSH data available.


Related in: MedlinePlus