Long-Term Safety and Efficacy of a Combination of Niacin Extended Release and Simvastatin in Patients with Dyslipidemia

Karas, Richard H.; Kashyap, Moti L.; Knopp, Robert H.; Keller, L; Bajorunas, Daiva R.; Davidson, Michael

doi:10.2165/00129784-200808020-00001

Cited by 57 publications

(68 citation statements)

References 24 publications

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“…In the OCEANS study, 68% of patients using an 8-week extended-release niacin and simvastatin titration schedule experienced flushing compared with approximately 74% of those using a 12-week titration. 57 Regimens of patients receiving the PGD 2 antagonist laropiprant along with extended-release niacin have consisted of a 2-step schedule: initiating niacin treatment at the relatively high daily dose of 1.0 g, which was maintained for 4 weeks, and then escalating to 2 g at treatment week 4 and maintaining this dose for 12 weeks. 142 In my practice, we use a combination of these 2 approaches, starting low (0.5 g/d) and going slowly (for a total of 8 weeks) until a stable dose of 1.0 g has been reached.…”

Section: Discussionmentioning

confidence: 99%

“…tients discontinued treatment because of flushing. [54][55][56][57][58][59][60] The long-term OCEANS (Open-Label Evaluation of the Safety and Efficacy of a Combination of Niacin Extended-Release and Simvastatin in Patients with Dyslipidemia) study showed that less than 40% of patients who experienced flushing in the first 12 weeks of treatment, when extended-release niacin/simvastatin doses were being escalated from 0.5 g/40 mg to 2.0 g/40 mg, did so during the following 12 weeks. 57 In the SEACOAST (Safety and Efficacy of a Combination of Niacin ER and Simvastatin in Patients With Dyslipidemia) trial, 27% of patients who experienced flushing while taking 1.0 g/20 mg of extended-release niacin/simvastatin (and 30% of patients taking 2.0 g/20 mg of extendedrelease niacin/simvastatin) during the first 12 weeks but who completed the study did not flush during the second 12 weeks.…”

Section: Frequencies Of Flushing and Related Discontinuations With Nimentioning

confidence: 99%

“…[54][55][56][57][58][59][60] The long-term OCEANS (Open-Label Evaluation of the Safety and Efficacy of a Combination of Niacin Extended-Release and Simvastatin in Patients with Dyslipidemia) study showed that less than 40% of patients who experienced flushing in the first 12 weeks of treatment, when extended-release niacin/simvastatin doses were being escalated from 0.5 g/40 mg to 2.0 g/40 mg, did so during the following 12 weeks. 57 In the SEACOAST (Safety and Efficacy of a Combination of Niacin ER and Simvastatin in Patients With Dyslipidemia) trial, 27% of patients who experienced flushing while taking 1.0 g/20 mg of extended-release niacin/simvastatin (and 30% of patients taking 2.0 g/20 mg of extendedrelease niacin/simvastatin) during the first 12 weeks but who completed the study did not flush during the second 12 weeks. 56 In the recent SUPREME (Study to Compare the Lipid Effects of Niacin Extended-Release and Simvastatin to Atorvastatin in Subjects With Hyperlipidemia or Mixed Dyslipidemia) trial, extended-release niacin was up-titrated more aggressively, from 1.0 g for treatment weeks 1 to 4 to 2.0 g for weeks 5 to 12 54 ; despite this, approximately 47% of patients experienced no flushing during weeks 1 to 4, 55% experienced no flushing during weeks 5 to 8, and 70% experienced no flushing during weeks 9 to 12 ( Figure 2).…”

Section: Frequencies Of Flushing and Related Discontinuations With Nimentioning

confidence: 99%

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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

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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

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Section: Discussionmentioning

confidence: 99%

Section: Frequencies Of Flushing and Related Discontinuations With Nimentioning

confidence: 99%

Section: Frequencies Of Flushing and Related Discontinuations With Nimentioning

confidence: 99%

See 1 more Smart Citation

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

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“…Recent studies have confirmed the superior efficacy of combining extended release niacin and simvastatin (3)(4). However, the rate of niacin discontinuation due to flushing is over 80% even with extended release niacin (32), and increases over the course of treatment (33)(34); moreover, the flush can not be reduced by ASA (325 mg/day), ibuprofen (200 mg/day) or selective PGD 2 receptor antagonists by more than 30% (11)(12)35).…”

Section: Discussionmentioning

confidence: 99%

A Quercetin Containing Supplement Reduces Niacin-Induced Flush in Humans

Kalogeromitros

Makris

Chliva

et al. 2008

Int J Immunopathol Pharmacol

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Coronary artery disease is associated with increased serum levels of cholesterol, triglycerides and LDL, but low levels of HDL. The most potent agent capable of reversing this trend is the vitamin nicotinic acid (niacin). However, compliance even with extended-release preparations and addition of acetylsalicylic acid (ASA) is hampered by the development of a feeling of erythema and burning ("flush"), especially on the face. We recently showed that the natural flavonoids quercetin and luteolin can eliminate "flush", as well as inhibit both niacin-induced plasma prostaglandin D, (PGD z ) and serotonin increase in an animal model. We conducted a pilot clinical study in humans. Four normal male subjects received (a) 1 g immediate release niacin either alone or after (b) the dietary formulation (Algonot-plus") containing 150 mg quercetin per capsule. Subjects completed a visual scale (l=no, 5=worst response) symptom assessment. Erythema and burning sensation scores were both 4.75±0.50 and lasted for 3.63±1.11 hours. After Algonot-plus" administration, both scores were reduced to 2.5±0.58 and lasted for only 1.68±O.70 hours. Quercetin also inhibited methylnicotinate-induced human mast cell PGD z release. These preliminary results suggest that quercetin could reduce niacin-induced "flush" in humans.Ingestion of the B 3-vitamin niacin (nicotinic acid) has been repeatedly shown to improve hypercholesterolemia and other lipoprotein abnormalities, while it also-increases HOL levels (1). Moreover, the combination of niacin with lovastatin has been shown to be superior to either agent alone (2-4). However, a serious limiting adverse effect is the development of significant facial erythema and warmth, known as "flush" that is more intense with immediate release than with extended release niacin (2, 5-6). Moreover, most of the over-the-counter formulations either do not contain sufficient niacin to have any effect or contain niacin metabolites that are ineffective (7).Niacin is thought to induce flush by stimulating the release of prostaglandin 02 (PG0 2) from the skin (8-9), most likely from dermal macrophages (10). However, co-administration of acetylsalicylic acid (ASA) does not reduce PGD 2 levels more than about 30% (II). Other measures used to reduce flush have included avoidance of alcohol and spicy foods with little benefit (12).We recently used a rat model of flush (13) and showed that niacin-induced skin vasodilation was accompanied by increased plasma PGD 2 , but also serotonin increases, both of which were inhibited along with the flush by the f1avonoids quercetin and luteolin (14). We therefore conducted a pilot clinical trial to investigate if a quercetin containing dietary supplement could inhibit niacin-induced flush in humans. MATERIALS AND METHODS MaterialsImmediate release macin caplets (250 mg each, SLO-NIACIN

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“…The randomized, 52-week OCEANS (Open-Label Evaluation of the Safety and Efficacy of a Combination of Niacin ER and Simvastatin in Patients with Dyslipidaemia) study [17] randomized patients to 8-or 12-week niacin ER/simvastatin titration schedules (maximum daily dosage 2000 mg/40 mg). Patients were withdrawn from the study if they did not reach LDL-C NCEP ATP III goals at 24 weeks.…”

Section: Is Longer-term Treatment Effective?mentioning

confidence: 99%

Niacin Extended Release (ER)/Simvastatin (Simcor®)

Lyseng‐Williamson

2010

Drugs R D

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Long-Term Safety and Efficacy of a Combination of Niacin Extended Release and Simvastatin in Patients with Dyslipidemia

Abstract: Treatment with NER/S 2,000/40 mg/day is well tolerated, has no unanticipated adverse events, and provides additional, clinically relevant improvements in multiple lipid parameters beyond statin monotherapy.

Cited by 57 publications

References 24 publications

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

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

A Quercetin Containing Supplement Reduces Niacin-Induced Flush in Humans

Niacin Extended Release (ER)/Simvastatin (Simcor®)

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