Effect of two aspirin pretreatment regimens on niacin-induced cutaneous reactions

Jungnickel, Paul W.; Maloley, Pierre A.; Tuin, Elton L. Vander; Peddicord, Tom E.; Campbell, James

doi:10.1046/j.1525-1497.1997.07118.x

Cited by 61 publications

(47 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Thus, to increase serum levels of HDL-C in patients with a moderate to high coronary risk is an important goal, whether or not LDL-C goals are achieved, since residual risks still persist. 44,46 Niacin (nicotinic acid) has antithrombotic effects associated with improvements in endothelial function and reduction of the inflammatory process in the vascular wall with stabilisation of the atherosclerotic plaque.…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

The importance of low serum levels of high-density lipoprotein cholesterol (HDL-C) as a cardiovascular risk factor

Espinosa-Larrañaga

Vejar-Jalaf

Medina-Santillán

2005

Diabetes and Vascular Disease Research

View full text Add to dashboard Cite

In order to discuss and establish a joint position on the treatment of low serum levels of high-density lipoprotein cholesterol (HDL-C), a group of experts involved in the care of people with dyslipidaemia and at risk of cardiovascular disease met in Miami, Florida, US, on 5th and 6th March 2005. The experts came from the Latin American countries Argentina, Brazil, Chile, Colombia, Ecuador, Guatemala, Mexico and Venezuela and had at least five years of experience in the care of patients with dyslipidaemia and low HDL-C. The main objective of the meeting was to discuss and propose a treatment for low serum HDL-C levels as a cardiovascular risk factor in patients and to create a group of useful recommendations in this regard, applicable to the daily clinical practice of physicians dealing with patients with dyslipidaemia and cardiovascular disease. This document describes the methodology developed to obtain these recommendations and presents the results of this academic meeting.

show abstract

Section: Resultsmentioning

confidence: 99%

“…If, despite these measures, flushing still occurs, the use of 325 mg of acetylsalicylic acid 30 minutes before taking ER niacin may suppress or minimise its occurrence. 46 In practice, less frequent and intense flushes occur with continued use of niacin.…”

Section: Pharmacological Treatmentmentioning

confidence: 99%

The importance of low serum levels of high-density lipoprotein cholesterol (HDL-C) as a cardiovascular risk factor

Espinosa-Larrañaga

Vejar-Jalaf

Medina-Santillán

2005

Diabetes and Vascular Disease Research

View full text Add to dashboard Cite

show abstract

“…However, despite complete suppression of niacin-evoked PGD 2 release by low doses of aspirin (81 mg/day), there are still signifi cant residual symptoms of fl ushing, even after pretreatment with higher doses (325 and 650 mg) ( 62,77,78 ) of aspirin which would suppress residual prostaglandin formation. A recent study has shown that aspirin only blocks vasodilation in hairy but not in glabrous skin ( 79 ).…”

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

“…Subject reports of flushing on a 100-mm visual analog scale were obtained Ϫ60, 0, 15, 30, 60, 90, 120, 180, and 240 min after administration of NA, as described in ref. 13. Measurements of cutaneous blood flow in the malar skin were also obtained in these subjects by using LDPI at 0, 20, and 45 min after the dose of NA.…”

Section: Measurement Of Na-induced Flushing Symptoms In Healthy Subjementioning

confidence: 99%

Antagonism of the prostaglandin D ₂ receptor 1 suppresses nicotinic acid-induced vasodilation in mice and humans

Cheng¹,

Wu²,

Wu³

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

262

188

View full text Add to dashboard Cite

Nicotinic acid (NA) is commonly used to treat dyslipidemia, but it elicits an adverse effect, termed flushing, which consists of cutaneous vasodilation with associated discomfort. An animal model of NA-induced flushing has been established in mice. As in humans, NA stimulated vasodilation in a dose-dependent manner, was associated with an increase of the vasodilatory prostaglandin (PG) D2 in plasma and could be blocked by pretreatment with aspirin. Two PGD2 receptors have been identified: PGD2 receptor 1 (DP1, also called DP) and PGD2 receptor 2 (DP2, sometimes termed CRTH2). DP2 does not mediate NA-induced vasodilation; the DP2-specific agonist DK-PGD2 (13,14-dihydro-15-keto-PGD2) did not induce cutaneous vasodilation, and DP2 ؊/؊ mice had a normal vasodilatory response to NA. By contrast, BW245C, a DP1-selective agonist, induced vasodilation in mice, and MK-0524, a DP1-selective antagonist, blocked both PGD2-and NA-induced vasodilation. NA-induced vasodilation was also studied in DP1 ؉/؉ , DP1 ؉/؊ , and DP1 ؊͞؊ mice; although NA-induced vasodilation depended almost completely on DP1 in female mice, it depended only partially on DP1 in male mice. The residual NA-induced vasodilation in male DP ؊͞؊ mice was aspirin-sensitive. Thus, in the mouse, DP1 appears to be an important component involved in NA-induced vasodilation, but other cyclooxygenase-dependent mechanisms also may be involved. A clinical study in healthy men and women demonstrated that treatment with MK-0524 reduced the symptoms of flushing and the increase in skin perfusion after the administration of NA. These studies suggest that DP1 receptor antagonism may be an effective means to suppress NA-induced flushing in humans.aspirin ͉ prostaglandin D2 receptor 1 antagonist ͉ MK-0524 ͉ niacin ͉ flushing N icotinic acid (NA), sometimes called niacin, is a watersoluble B vitamin that has been used to treat dyslipidemia for almost 50 years (1, 2). Used in high doses, it reduces plasma low-density lipoprotein cholesterol, apolipoprotein B, triglycerides, and lipoprotein(a) and increases high-density lipoprotein cholesterol and apolipoprotein A-I (3, 4). NA has been shown to have cardiovascular benefit when used alone or in combination with statins (hydroxymethylglutaryl-CoA reductase inhibitors) in several clinical trials (5-7).Despite these demonstrated beneficial effects, widespread use of NA for dyslipidemia has been limited by symptoms of flushing, which is associated with cutaneous vasodilation of the face, neck, and torso that occurs in nearly all patients (5, 8). Administration of cyclooxygenase (COX) inhibitors, such as aspirin and indomethacin, before ingestion of NA can attenuate the NA-induced cutaneous reactions in most patients (9-13) without affecting its plasma free fatty acid-lowering effect (14). However, doses of aspirin of 325 mg or higher are generally required to significantly block flushing (15), which compromises the utility of this approach for the chronic suppression of flushing. Although the mechanism of action of NA-induced flushi...

show abstract

Effect of two aspirin pretreatment regimens on niacin-induced cutaneous reactions

Abstract: An aspirin regimen of 325 mg is effective in suppressing niacin-induced cutaneous reactions. Increasing the dose to 650 mg does not provide additional benefit.

Cited by 61 publications

References 15 publications

The importance of low serum levels of high-density lipoprotein cholesterol (HDL-C) as a cardiovascular risk factor

The importance of low serum levels of high-density lipoprotein cholesterol (HDL-C) as a cardiovascular risk factor

Niacin, an old drug with a new twist

Antagonism of the prostaglandin D ₂ receptor 1 suppresses nicotinic acid-induced vasodilation in mice and humans

Contact Info

Product

Resources

About

Effect of two aspirin pretreatment regimens on niacin-induced cutaneous reactions

Abstract: An aspirin regimen of 325 mg is effective in suppressing niacin-induced cutaneous reactions. Increasing the dose to 650 mg does not provide additional benefit.

Cited by 61 publications

References 15 publications

The importance of low serum levels of high-density lipoprotein cholesterol (HDL-C) as a cardiovascular risk factor

The importance of low serum levels of high-density lipoprotein cholesterol (HDL-C) as a cardiovascular risk factor

Niacin, an old drug with a new twist

Antagonism of the prostaglandin D 2 receptor 1 suppresses nicotinic acid-induced vasodilation in mice and humans

Contact Info

Product

Resources

About

Antagonism of the prostaglandin D ₂ receptor 1 suppresses nicotinic acid-induced vasodilation in mice and humans