Lipid-modifying efficacy and tolerability of extended-release niacin/laropiprant in patients with primary hypercholesterolaemia or mixed dyslipidaemia

Maccubbin, Darbie; Bays, Harold; Olsson, Anders; Elinoff, V.; Elis, Avishay; Mitchel, Yale; Sirah, Waheeda; Betteridge, Abigaile; Reyes, Reinabelle; Yu, Qinfen; Kuznetsova, Olga M.; Sisk, Christine McCrary; Pasternak, Richard C.; Paolini, John F.

doi:10.1111/j.1742-1241.2008.01938.x

Cited by 115 publications

(128 citation statements)

References 25 publications

Supporting

Mentioning

121

Contrasting

Unclassified

Order By: Relevance

“…Antagonism of DP1 suppresses niacininduced vasodilation signifi cantly in mice and humans ( 80 (85)(86)(87)(88)(89)(90). Interestingly, despite tachyphylaxis of niacin-induced PGD 2 within a week ( 75 ), LRPT's anti-fl ushing effect is reportedly sustained for months ( 82,83 ).…”

Section: Effects On Hdlmentioning

confidence: 99%

Niacin, an old drug with a new twist

Song

FitzGerald

2013

Journal of Lipid Research

View full text Add to dashboard Cite

This article is available online at http://www.jlr.org the only approved drug with such an effect ( 1 ). It has proven to be an attractive option for those intolerant of statin treatment. It has been demonstrated to reduce risk of atherosclerotic cardiovascular disease ( 4 ). The clinical use of niacin has been markedly limited by cutaneous fl ushing. The molecular target of niacin responsible for lipid metabolic changes and fl ushing was unknown until 2003 ( 5-7 ), when the niacin receptor, namely HM74A in humans and PUMA-G in mice, was discovered. The niacin receptor, also known as GPR109A, was shown to be activated by niacin and to mediate its antilipolytic effect as well as the fl ushing effect ( 8-10 ). Interest in niacin has risen because there is still signifi cant residual risk in patients with intensive statin therapy ( 11 ). However, recent outcome trials ( 11, 12 ) failed to show niacin's benefi t on top of statin therapy in lipid-targeted approaches to reduce major cardiovascular events in high-risk patients. In this review we will summarize the pharmacology of niacin, with a particular emphasis on recent outcome trials, including discussion of their limitations . NIACIN'S LIPID EFFECTSNiacin has long been shown to have effects on lipids ( 13 ). Niacin increases high density lipoprotein cholesterol (HDLc), but reduces low density lipoprotein cholesterol (LDLc), VLDL cholesterol, and triglycerides (TGs) ( 14 ) Niacin is also known as vitamin B3. Chronic dietary defi ciency of niacin can cause pellagra ( 1 ). It is a precursor to NAD+/NADH and NADP+/NADPH, both of which play essential metabolic roles in living cells ( 2 ). Niacin has been used for more than half a century in the treatment of dyslipidemia. When Altschul, Hoffer, and Stephen ( 3 ) discovered that niacin could lower plasma levels of cholesterol, it was

show abstract

Section: Effects On Hdlmentioning

confidence: 99%

Niacin, an old drug with a new twist

Song

FitzGerald

2013

Journal of Lipid Research

View full text Add to dashboard Cite

show abstract

“…In the pivotal laropiprant phase 3 study (study 020), 2.9% of the laropiprant and extended-release niacin group experienced nausea (vs 2.0% with extended-release niacin alone) and 2.6% experienced diarrhea (vs 1.8%). 140 Across laropiprant studies 020, 022, and 054, 16.5% of the laropiprant and extended-release niacin groups experienced gastrointestinal adverse events (vs 11.7% of the extendedrelease niacin group).…”

Section: Discussionmentioning

confidence: 99%

“…139 In a pivotal phase 3 study (study 020), approximately 31% of patients who were using adjunctive laropiprant and extended-release niacin (1.0 g) experienced moderate or greater flushing during treatment week 1 compared with 56% receiving monotherapy with 1.0 g of extended-release niacin (P<.001) and 6% taking placebo. 140 Corresponding proportions of patients with severe or extreme flushing were 14% in the laropiprant and extended-release niacin group and 33% in the extended-release niacin group (P<.001). 140 During treatment weeks 2 to 24 in study 020, 14% of patients taking laropiprant and extended-release niacin experienced 1 day per week or more with moderate or greater flushing compared with 29% of those taking extended-release niacin monotherapy (P<.001) and approx- For personal use.…”

mentioning

confidence: 92%

“…140 Corresponding proportions of patients with severe or extreme flushing were 14% in the laropiprant and extended-release niacin group and 33% in the extended-release niacin group (P<.001). 140 During treatment weeks 2 to 24 in study 020, 14% of patients taking laropiprant and extended-release niacin experienced 1 day per week or more with moderate or greater flushing compared with 29% of those taking extended-release niacin monotherapy (P<.001) and approx- For personal use. Mass reproduce only with permission from Mayo Clinic Proceedings a .…”

mentioning

confidence: 92%

“…140 During the maintenance phase, patients in the laropiprant and extendedrelease niacin group experienced approximately 1 day of moderate or greater flushing per patient-month compared with 1 day per patient-week in the extended-release niacin group. Commenting on these data, the authors contended that "tolerance to this level of flushing is incomplete during at least a 6-month period."…”

mentioning

confidence: 99%

See 2 more Smart Citations

A “Hot” Topic in Dyslipidemia Management—“How to Beat a Flush”: Optimizing Niacin Tolerability to Promote Long-term Treatment Adherence and Coronary Disease Prevention

Jacobson

2010

Mayo Clinic Proceedings

View full text Add to dashboard Cite

Niacin is the most effective lipid-modifying agent for raising highdensity lipoprotein cholesterol levels, but it also causes cutaneous vasodilation with flushing. To determine the frequency of flushing in clinical trials, as well as to delineate counseling and treatment approaches to prevent or manage flushing, a MEDLINE search was conducted of English-language literature from January 1, 19851, , through April 7, 2009. This search used the title keywords niacin or nicotinic acid crossed with the Medical Subject Headings adverse effects and human. Niacin flushing is a receptormediated, mainly prostaglandin D 2 -driven phenomenon, the frequency, onset, and duration of which are largely determined by the distinct pharmacological and metabolic profiles of different niacin formulations. Subjective assessments include ratings of redness, warmth, itching, and tingling. In clinical trials, most (>60%) niacin users experienced mild or moderate flushing, which tended to decrease in frequency and severity with continued niacin treatment, even with advancing doses. Approximately 5% to 20% of patients discontinued treatment because of flushing. Flushing may be minimized by taking niacin with meals (or at bedtime with a low-fat snack), avoiding exacerbating factors (alcohol or hot beverages), and taking 325 mg of aspirin 30 minutes before niacin dosing. The current review advocates an initially slow niacin dose escalation from 0.5 to 1.0 g/d during 8 weeks and then from 1.0 to 2.0 g in a single titration step (if tolerated). Through effective counseling, treatment prophylaxis with aspirin, and careful dose escalation, adherence to niacin treatment can be improved significantly. Wider implementation of these measures should enable higher proportions of patients to reach sufficient niacin doses over time to prevent cardiovascular events. Proc. 2010;85(4):365-379 GPR = G i protein-coupled receptor; HDL-C = high-density lipoprotein cholesterol; NSAID = nonsteroidal anti-inflammatory drug; PG = prostaglandin; RCT = randomized controlled trial R educing low-density lipoprotein cholesterol levels is the primary treatment for preventing cardiovascular disease, largely because of robust evidence from randomized controlled trials (RCTs) involving statins. Mayo Clin

show abstract