Prolonged-release Nicotinic Acid Research Articles

Pharmacokinetics and dose recommendations of Niaspan(R) in chronic kidney disease and dialysis patients

Niaspan® is an extended-release formulation of nicotinic acid with improved tolerability compared with the immediate-release and sustained-release formulations. It is used to treat hypertriglyceridaemia with low high-density lipoprotein levels. This type of dyslipidaemia frequently appears in patients with chronic kidney disease (CKD). Dose recommendations for these patients are not available because pharmacokinetic data are missing. The present study was performed to analyse the pharmacokinetics of prolonged-release nicotinic acid in CKD and in dialysis patients to derive dose recommendations. Ten dialysis patients and eight patients with CKD were enrolled in a prospective, three-period, open-label pharmacokinetic study. They received in the first week 500 mg Niaspan® per day, in the second week 1000 mg/day and in the third week 1500 mg/day. On the fourth day of every treatment unit, 11 plasma samples were collected for 24 h post-dose and analysed for nicotinic acid (NA) and its metabolites nicotinamide and nicotinuric acid (NUA). Median plasma NA concentrations in subjects with CKD were obviously higher than in dialysis patients, but not higher than reported in patients without renal impairment. t(max) of NA were on average 0.75 h in dialysis patients and 3.0 h in CKD patients and, therefore, especially for dialysis patients, clearly shorter than expected for extended-release formulations. It is particularly noticeable that the AUC, C(max) and t(1/2) of the metabolite NUA are significantly higher in dialysis patients in comparison to CKD patients. This may indicate that the dialysis was not effective in removing this metabolite. However, there was no correlation between the incidence of flush and the concentration of NUA. Another possibility could be a drug-drug interaction with omeprazole via CYP450 enzymes. These data suggest that no dose adjustment of Niaspan® is necessary in patients with renal impairment. Despite an extended-release formulation of NA, we could not detect a delay in t(max) especially in dialysis patients. We found no correlation between the incidence of flush and the NUA concentration. Furthermore, there were hints of an interaction with omeprazole.

Prolonged-Release Nicotinic Acid in Patients with Atherosclerotic Disease in The Netherlands

Objectives: High-density lipoprotein (HDL) cholesterol elevation is associated with an improved outcome in patients with atherosclerotic disease. Niaspan®, a prolonged-release nicotinic acid, was evaluated during the Niaspan-Induced HDL Elevation for Optimizing Risk Control (NEMO) study in The Netherlands. Methods: NEMO was a 6-month, prospective, observational, multicentre, open-label study. Niaspan was prescribed in statin-treated patients with known or suspected atherosclerotic disease. The main outcome measures were treatment-related adverse drug reactions (ADRs) and effects on lipids and cardiovascular-risk score based on the algorithm derived from the Prospective Cardiovascular Münster study. Results: 612 patients were included in The Netherlands. Flushing was the most common ADR (29% of patients during the first month of treatment). The main reasons for treatment discontinuation were flushing (10.5%), patient request (8.0%) and being lost to follow-up (6.0%). About half of all patients (52%) continued treatment after the study. Tolerability was rated ‘good’ or ‘very good’ in 54% of these patients. HDL cholesterol increased by 23% from baseline, and triglycerides were reduced by 16%, with little change in low-density lipoprotein or total cholesterol. Cardiovascular risk score was reduced by 3.3 points. Conclusions: The use of the prolonged-release nicotinic acid Niaspan in patients with or at risk for atherosclerotic disease showed good tolerability, a marked increase in HDL cholesterol and a reduced cardiovascular risk score.

Étude d’utilisation de l’acide nicotinique a libération prolongée en France chez des patients en prévention secondaire sous statine avec persistance d’un taux bas de HDL-c

HDL-c is a potent predictor of cardiovascular risk in all epidemiologic studies, especially as secondary prevention, regardless of LDL-c level obtained on statin treatment. The objective of this longitudinal observational study was to investigate the effects of prolonged-release nicotinic acid in high cardiovascular risk patients on statin treatment and with low HDL-c. Method The selected patients of both genders, aged over 18 years patients showed primary hypercholesterolemia or mixed hyperlipidemia, received statin treatment as secondary prevention and had a HDL-c level ≤ 0.40 g/l. Treatment with prolonged-release nicotinic acid was initiated according to the approved dosing regimen. Results The analysis was performed in 368 patients selected by 224 cardiologists. Mean follow-up time was 103 days with a daily dose of prolonged-release nicotinic acid of 1076 mg. Mean LDL-c changed from 1.08 to 1 g/l ( p < 0.001), mean HDL-c from 0.34 g to 0.42 g/l (+23%, p < 0.001) and triglycerides from 1.81 to 1.53 g/l ( p < 0.001). Eighty nine percents of treatment discontinuations ( n = 107) were due to side effects, almost half of them being flushes (46.3%). The incidence of flushes was significantly more rapidly reduced in patients taking aspirin ( p < 0.001). Conclusion Expected efficacy results were obtained, especially with a very significant increase in HDL-c. The adjunction of prolonged-release nicotinic acid in high risk patients on statin treatment as secondary prevention and with low HDL-c constitutes an interesting strategy.

Niacin Lowers Serum Phosphate and Increases HDL Cholesterol in Dialysis Patients

Adverse effects complicate the use of drugs that are prescribed for phosphate control in dialysis patients. Alternative treatment options are needed. Nicotinic acid inhibits intestinal phosphate reabsorption and increases HDL cholesterol. This study tested the phosphate-lowering and HDL-increasing effect of Niaspan (prolonged-release nicotinic acid) in patients who were undergoing dialysis. Efficacy, safety, and tolerability of Niaspan were prospectively studied. Twenty dialysis patients, who were receiving a stable dosage of a calcium salt-containing drug for phosphate control, received after a 2-wk washout period Niaspan for 12 wk. Patients were started on 375 mg/d, and the dosage was increased every 2 wk to achieve 500, 1000, 1500, and 2000 mg/d, respectively. Clinical and laboratory parameters were prospectively recorded in patients who tolerated a target dosage of > or = 1000 mg/d. Seventeen patients tolerated > or = 1000 mg/d Niaspan (mean dosage 1470 +/- 110 mg/d). Niaspan treatment for 12 wk decreased serum phosphate values from 7.2 +/- 0.5 to 5.9 +/- 0.6 mg/dl (P < 0.015). In contrast, Niaspan did not affect serum calcium levels. A significant increase in HDL cholesterol from 40 +/- 3.2 to 59 +/- 5.5 mg/dl (34%) was also observed with Niaspan (P = 0.0005). Niaspan effectively lowered serum phosphate levels and significantly increased HDL cholesterol. Niaspan may provide an alternative or adjunctive treatment option in dialysis patients.

Cost-effectiveness of raising HDL cholesterol by adding prolonged-release nicotinic acid to statin therapy in the secondary prevention setting: a French perspective

To evaluate the cost-effectiveness of raising high-density lipoprotein cholesterol (HDL-C) with add-on nicotinic acid in statin-treated patients with coronary heart disease (CHD) and low HDL-C, from the French healthcare system perspective. Computer simulation economic modelling incorporating two decision analytic submodels was used. The first submodel generated a cohort of 2000 patients and simulated lipid changes using baseline characteristics and treatment effects from the ARterial Biology for the Investigation of the Treatment Effects of Reducing cholesterol (ARBITER 2) study. Prolonged-release (PR) nicotinic acid (1 g/day) was added in patients with HDL-C < 40 mg/dl (1.03 mmol/l) on statin alone. The second submodel used standard Markov techniques to evaluate long-term clinical and economic outcomes based on Framingham risk estimates. Direct medical costs were accounted from a third party payer perspective [2004 Euros (euro)] and discounted by 3%. Addition of PR nicotinic acid to statin therapy resulted in substantial health gain and increased life expectancy, at a cost well within the threshold (< 50,000 euros per life year gained) considered good value for money in Western Europe. Raising HDL-C by adding PR nicotinic acid to statin therapy in CHD patients was cost-effective in France at a level considered to represent good value for money by reimbursement authorities in Europe. This strategy was highly cost-effective in CHD patients with type 2 diabetes.

Prolonged-release nicotinic acid for the management of dyslipidemia: an update including results from the NAUTILUS study

Low HDL-cholesterol (<1.02 mmol/L [40 mg/dL] in men or <1.29 mmol/L [50 mg/dL] in women) occurs in about one-third of European patients with dyslipidemia and is an independent cardiovascular risk factor. Simultaneous correction of low HDL-cholesterol and high total-cholesterol and LDL-cholesterol may provide reductions in cardiovascular morbidity and mortality beyond those possible with statins alone. Nicotinic acid (niacin in the US) is the most effective means of increasing HDL-cholesterol available and has been shown to reduce cardiovascular event rates significantly. Niaspan (prolonged-release nicotinic acid) provides a convenient, once-daily means of administering nicotinic acid. Clinical studies with Niaspan have demonstrated marked, long-term increases in HDL-cholesterol with additional useful benefits on triglycerides, LDL-cholesterol, and lipid sub-profiles. The NAUTILUS study demonstrated the beneficial efficacy and tolerability profiles of Niaspan in a usual-care setting. The most common side-effect of Niaspan is flushing, which infrequently causes treatment discontinuation and which usually subsides over continued treatment. The ARBITER 2 and ARBITER 3 studies showed 1-2 years of treatment with Niaspan plus a statin induced regression of atherosclerosis in patients with coronary artery disease. The effect of Niaspan-statin treatment, relative to a statin alone, on clinical cardiovascular outcomes is currently under evaluation. Niaspan represents a practical means of correcting low HDL-cholesterol, an independent risk factor for adverse cardiovascular outcomes.

Correction of low HDL cholesterol to reduce cardiovascular risk: practical considerations relating to the therapeutic use of prolonged-release nicotinic acid (Niaspan®)

Substantial residual cardiovascular risk persists despite effective LDL lowering treatment in populations at elevated risk for adverse cardiovascular outcomes. Low HDL cholesterol is an independent cardiovascular risk factor and occurs in about one-third of patients treated for dyslipidaemia in Europe. Moreover, randomised intervention studies have shown that increasing HDL cholesterol improves cardiovascular outcomes. Correcting low HDL cholesterol therefore presents a rational and proven strategy for intervention to produce further reductions in cardiovascular risk beyond those possible with a statin alone. Nicotinic acid (niacin in the USA) is the most effective agent currently available for increasing levels of HDL cholesterol. A once-daily, prolonged-release formulation of nicotinic acid (Niaspan) is as effective on HDL cholesterol as the immediate-release formulation, and is equally effective at increasing HDL cholesterol whether or not patients are already taking a statin. Niaspan also shares the antiatherogenic benefit of nicotinic acid, and induced regression of atherosclerosis in patients with cardiovascular disease during a period of treatment of up to 2 years. The incidence of flushing, the principal side effect of nicotinic acid, is lower with Niaspan than with immediate-release nicotinic acid. Simple practical measures are available to minimise the incidence and impact of flushing, including careful dose titration and avoiding hot or spicy foods near the time of ingestion of Niaspan. The potential for hepatotoxicity, muscle toxicity or marked exacerbation of hyperglycaemia in diabetes with Niaspan is very low, with or without concomitant statin treatment. Niaspan provides a practical means of delivering the cardioprotective benefits associated with correction of low HDL cholesterol.

Safety and tolerability of prolonged-release nicotinic acid in statin-treated patients

ABSTRACTObjective: To evaluate the safety and tolerability of prolonged-release nicotinic acid (Niaspan) added to statin therapy in patients at increased cardiovascular risk.Methods: This was a 6-month, prospective, observa­tional, multicentre, open-label evaluation of prolonged-release nicotinic acid (maximum dose 2000 mg/day) in statin-treated patients with cardiovascular disease and/or type 2 diabetes. The primary endpoint was the safety and tolerability of prolonged-release nicotinic acid, with special regard to treatment-related adverse drug reactions (ADRs). Secondary endpoints were changes in lipids and 10-year cardiovascular risk (Prospective Cardiovascular Münster (PROCAM) score).Results: The study population included 1053 patients: 50% had hypertension, diabetes and/or metabolic syndrome (National Cholesterol Education Program/Adult Treatment Panel III criteria) and 80% had cardiovascular disease. Flushing (mostly mild or moderate) occurred in 430 patients (40.8%). Other ADRs occurred in 125 patients (12.5%), most commonly pruritus (2.7%), gastro­intestinal symptoms (3.8%) and nervous system-related complaints (3.8%). Serious ADRs were uncommon (0.6%). All patients recovered completely from these ADRs after treatment discontinuation. In total, 11.1% of the patients discontinued study medication for flushing and 8.4% for other ADRs. There was no evidence of hepatotoxicity or myopathy. New-onset hyperglycaemia was negligible. Overall tolerability of prolonged-release nicotinic acid treatment (n = 734 patients at closeout) was ‘very good’ in 130 (17.7%), ‘good’ in 262 (35.7%), and ‘acceptable’ in 144 (19.6%) patients. High-density lipoprotein (HDL) cholesterol increased by 23%, triglycerides decreased by 15% and LDL-C decreased by 4%.Conclusions: Prolonged-release nicotinic acid was safe and generally well tolerated and effective in combination with statin therapy in patients at high risk of cardio­vascular events, with a side-effect profile consistent with previous clinical experience.

Reducing residual cardiovascular risk: the relevance of raising high-density lipoprotein cholesterol in patients on cholesterol-lowering treatment

Reducing low-density lipoprotein cholesterol (LDL-C) with statin therapy represents the cornerstone of dyslipidaemia management in patients with cardiovascular disease, as reflected in current treatment guidelines. Yet even among statin-treated patients who achieve LDL-C targets (&lt; 2.59 mmol/L [100 mg/dL]), the residual risk of further cardiovascular events remains unacceptably high. Although clinical studies indicate that intensive LDL-C lowering may provide some additional benefit, this does not suppress the excess cardiovascular risk sufficiently. This European Expert Panel therefore recognises that there is an unmet clinical need in the management of these patients. Additional intervention to modify other clinically important risk factors should be viewed as a priority. A reduced level of high-density lipoprotein cholesterol (HDL-C) &lt; 1.03 mmol/L (40 mg/dL) in men and &lt; 1.29 mmol/L (50 mg/dL) in women is an important independent predictive factor for coronary heart disease. HDL-C levels are also predictive of cardiovascular risk in statin-treated patients, irrespective of their LDL-C levels. Therefore, HDL-C represents a logical therapeutic target for reducing cardiovascular risk further in statin-treated patients, including those who achieve LDL-C targets. Given that low HDL-C is common among dyslipidaemic patients with cardiovascular disease, a therapeutic strategy aimed at effectively raising HDL-C, while at the same time lowering LDL-C to target levels, would be expected to offer clinical benefit beyond that achieved through LDL-C reduction alone. Although both nicotinic acid and fibrates raise HDL-C, nicotinic acid has greater potency. Studies show that combination therapy with prolonged-release (PR) nicotinic acid and a statin has an acceptable tolerability profile, normalises an atherogenic lipoprotein profile, and is able to induce regression of atherosclerosis and reduce coronary risk in patients with established cardiovascular disease and suboptimal HDL-C levels. In conclusion, this European Expert Panel recommends that combination therapy with a statin and an HDL-C raising agent, such as PR nicotinic acid, should be considered in these patients, who remain at high residual risk despite achieving target LDL-C levels with statin monotherapy. Ongoing studies are essential to confirm the clinical outcome benefits of this approach.

Nicotinic acid and other therapies for raising high-density lipoprotein

The purpose of this review is to describe the high-density-lipoprotein-raising effect of nicotinic acid and the clinical effects of treatment on cardiovascular diseases, particularly in combination with statins. Other treatments for raising high-density lipoprotein, including changes in lifestyle, other drugs and infusions of 'synthetic' (reconstituted) high-density lipoprotein will be summarized. Treatment of atherosclerotic cardiovascular disease with nicotinic acid and statin results in a pronounced increase of protective high-density lipoprotein cholesterol and reduces morbidity/mortality. Addition of prolonged-release nicotinic acid to ongoing treatment with statin raises high-density lipoprotein cholesterol and induces regression of atherosclerosis that otherwise would progress during statin treatment. Several new high-density lipoprotein-raising drugs in clinical trials are reported. New proposed mechanisms for the broad-spectrum lipid effects of nicotinic acid are described. Low plasma concentration of high-density lipoprotein is an important risk factor for atherosclerotic cardiovascular disease. Nicotinic acid has the uncomfortable but harmless side effect of flush. Prolonged-release nicotinic acid gives rise to less flush than immediate-release nicotinic acid. Treatment with nicotinic acid and statin targets the two independent lipid risk factors of low high-density lipoprotein and high low-density lipoprotein and has clinical benefits in secondary prevention of atherosclerotic cardiovascular disease.

Lipoprotein(a)

In this issue of Stroke , the Atherosclerosis Risk in Communities (ARIC) study provides evidence that lipoprotein(a) [Lp(a)] is a significant predictor of stroke.1 This is an important finding, because ARIC is both large and prospective. Over 14 000 patients were enrolled in 1987 to 1989, and during 13.5 years of follow-up, they experienced 496 ischemic strokes. Lp(a) remained a significant predictor of stroke after adjustment for age, race, systolic blood pressure, antihypertensive medication, smoking status, use of postmenopausal hormone therapy, diabetes, LDL cholesterol, HDL cholesterol, fibrinogen, and von Willebrand factor. It thus seems likely that Lp(a) is potentially an important treatable risk factor. But what is Lp(a), and how does it relate to atherosclerosis and cardiovascular events? A meta-analysis of prospective studies of coronary events2 seems to establish that Lp(a) is also a predictor of myocardial infarction, but numerous studies indicate that it does not seem to predict the burden of atherosclerosis as assessed by intima-media thickness,3,4 except perhaps in patients with renal …

NAUTILUS (Safety and tolerability of Niaspan®): a subgroup analysis in patients with diabetes

The multiceNtre, open, uncontrolled sAfety and tolerability stUdy of a modified-release nicoTinic acId formuLation in sUbjects with dySlipidaemia and low HDL-cholesterol (NAUTILUS) trial was designed to evaluate the safety and tolerability of prolonged-release nicotinic acid (Niaspan®) in patients treated for dyslipidaemia in a usual care setting in Germany. The dyslipidaemia was inadequately controlled by diet, including low high-density lipoprotein cholesterol (HDL-C) (&lt; 1.0 mmol/L [&lt; 40 mg/dL] in men and &lt; 1.2 mmol/L [&lt;46 mg/dL] in women). This analysis focuses on the tolerability and safety of Niaspan® in patients with diabetes. Diabetic and non-diabetic subjects reported similar incidences of all-cause adverse events (AE; 59.9% vs. 60.8%, respectively), serious AE (SAE; 4.0% vs. 3.4%, respectively) and withdrawals for AE (17.6% vs. 16.4%). Flushing was the most common side effect, as expected (42% of patients in each group), but &lt; 10% withdrew for flushing. There was no indication of hepatotoxicity or serious muscle toxicity in diabetic or non-diabetic subjects. Changes in glycaemic parameters were small (mean changes in diabetic subjects of +0.2% HbA1C and +0.4 mmol/L [+8 mg/dL] for fasting plasma glucose), despite marked reductions in the intensity of antidiabetic therapy in about one third of patients. Niaspan® was equally effective in diabetic or non-diabetic subjects in increasing HDL-C (+24% in each group) and decreasing triglycerides (-12% and -13%, respectively). Niaspan® was well tolerated in patients with type 2 diabetes and the results of NAUTILUS support its use for correction of low HDL-C in this population.

Evaluation of the safety and tolerability of prolonged-release nicotinic acid in a usual care setting: the NAUTILUS study

ABSTRACTObjective: The main objective was to evaluate the safety and tolerability of prolonged-release nicotinic acid (niacin; Niaspan) in an usual care setting with patients receiving treatment for dyslipidaemia in Germany: the multiceNtre, open, uncontrolled sAfety and tolerability stUdy of a modified-release nicoTinic acId formuLation in sUbjects with dySlipidaemia and low HDL-cholesterol (NAUTILUS).* Niaspan is a registered trade name of Merck KGaA, Darmstadt, GermanyResearch design and methods: This was a multicentre, open-label, 15‐week study. Eligible patients had a diagnosis of dyslipidaemia with lipids inadequately controlled by 4 weeks of diet treatment. Additionally, patients had low HDL-cholesterol (< 1.03 mmol/L [< 40 mg/dL]) in men and < 1.29 mmol/L [< 50 mg/dL] in women), and had triglycerides < 9.03 mmol/L (< 800 mg/dL). Exclusion criteria included uncontrolled diabetes (HbA1C > 9%), significant hepatic, vascular or renal disease. The target dose was 2000 mg once daily.Main outcome measures: The main objective was to evaluate the safety and tolerability of prolonged-release nicotinic acid [incidence of adverse events (AE) and serious AE] in the overall population (the safety population). Efficacy parameters (lipid parameters) were also measured in the intent-to-treat population.Results: A total of 566 patients were recruited, mostly with metabolic syndrome (39.4%), mixed hypercholesterolaemia (31.6%), isolated low HDL-cholesterol and markedly elevated cardiovascular risk for other reasons (10.8%), and primary hypercholesterolaemia (8.8%), according to NCEP/ATP III guidelines. The target dose was achieved by 65% of patients. Flushing was the most common side-effect (42%), as expected, and 9.7% withdrew for flushing. Other drug-related AEs occurred at low frequency (18.6%), and 8.7% withdrew for an AE other than flushing. Most AEs were mild or moderate in severity. Serious AEs considered possibly related to treatment occurred in three patients (0.5%); all resolved following treatment withdrawal. There was no hepatotoxicity or serious muscle AE.Conclusions: Prolonged-release nicotinic acid was well tolerated, and these results support its use in the management of patients at elevated cardiovascular risk due to low HDL-cholesterol.

Mo-P5:346 Health economic study of raising HDL-C with prolonged-release nicotinic acid (NIASPAN® LP) when added to statin therapy in dyslipidemic patients

Mo-P5:346 Health economic study of raising HDL-C with prolonged-release nicotinic acid (NIASPAN® LP) when added to statin therapy in dyslipidemic patients

Th-P16:336 Safety and tolerability of niaspan (prolonged-release nicotinic acid) in a usual care setting (results of the German nautilus study)

Th-P16:336 Safety and tolerability of niaspan (prolonged-release nicotinic acid) in a usual care setting (results of the German nautilus study)

Tu-W29:4 Cost-effectiveness of prolonged-release nicotinic acid (NIASPAN® ER) for statin-treated patients at LDL-C goal but remaining at risk due to low HDL-C

Tu-W29:4 Cost-effectiveness of prolonged-release nicotinic acid (NIASPAN® ER) for statin-treated patients at LDL-C goal but remaining at risk due to low HDL-C

Nicotinic acid in the management of dyslipidaemia associated with diabetes and metabolic syndrome: a position paper developed by a European Consensus Panel

ABSTRACTIndividuals with type 2 diabetes and metabolic syndrome are at markedly increased risk of cardiovascular morbidity and mortality. The increasing prevalence of both conditions poses a major challenge for clinicians in the 21st century. Both diabetes and metabolic syndrome are associated with a clustering of cardiovascular risk factors. In particular, dyslipidaemia characterised by low plasma levels of high-density lipoprotein cholesterol (HDL‐C), elevated triglycerides and an increase in small, dense low‐density lipoprotein (LDL) particles (the lipid triad), has been established as the most important modifiable risk factor for coronary heart disease (CHD).Current treatment guidelines recognise the increased CHD risk associated with diabetes and metabolic syndrome and focus on LDL-C lowering with statin treatment, in addition to dietary and lifestyle modification, as the primary lipid-modifying therapy. However, while there is no doubt that statin therapy significantly reduces CHD risk in these patients, their residual absolute risk remains higher than in individuals without diabetes or metabolic syndrome. Thus, there is a clear need to target other aspects of lipoprotein metabolism, notably low HDL-C and hypertriglyceridaemia, to further reduce CHD risk. Combining statin therapy (targeting LDL-C) with interventions that also modify low HDL-C and elevated triglycerides could be a useful strategy to optimise CHD risk reduction. Cautious combination of a fibrate or nicotinic acid with a statin is useful for the management of combined dyslipidaemia. Nicotinic acid is the more potent agent for raising HDL-C (by up to 29% at clinically recommended doses). It also substantially reduces triglycerides and LDL-C, and promotes a shift from small, dense LDL to larger, more buoyant LDL particles. Preliminary clinical data suggest that combining nicotinic acid with a statin will produce a greater reduction in cardiovascular risk in patients with diabetes and metabolic syndrome than statin monotherapy alone. Nicotinic acid is also safe for use in patients with diabetes, with no evidence of clinically relevant deterioration in glycaemic control at recommended doses (≤ 2 g/day). On review of the available evidence, this European Consensus Panel recommends the combination of nicotinic acid and a statin, together with lifestyle modification, as a useful strategy to lower CHD risk in patients with diabetes and metabolic syndrome. Prolonged-release nicotinic acid with improved tolerability compared with previous formulations may have obvious advantages for use in this setting.

Prolonged-Release Nicotinic Acid

Prolonged-release (PR) nicotinic acid (niacin) [Niaspan] is an oral, once-daily formulation of the lipid-modifying drug designed to produce less vasodilatory flushing than crystalline immediate-release (IR) nicotinic acid and less hepatotoxicity than previous sustained-release formulations of nicotinic acid.PR nicotinic acid appears to retain the same level of efficacy as crystalline IR nicotinic acid and be better tolerated than older nicotinic acid formulations. Nicotinic acid has beneficial effects on all traditional blood lipid and lipoprotein fractions and is the most effective agent for increasing high-density lipoprotein (HDL)-cholesterol (HDL-C) and reducing lipoprotein(a). The effects of PR nicotinic acid are often additive when used in combination with HMG-CoA reductase inhibitors (statins), making it a useful addition when lipid goals are not achieved with the usual statin monotherapy or when additional correction of a specific lipid abnormality is required. PR nicotinic acid also slows atherosclerotic progression and even appears to produce regression of atherosclerosis in patients on stable statin therapy. PR nicotinic acid is a logical drug choice for treating atherogenic dyslipidaemia commonly associated with type 2 diabetes mellitus and the metabolic syndrome, and has been shown to be effective in patients with diabetes without adversely affecting glycaemic control in the majority of patients. The incidence of vasodilatory flushing with PR nicotinic acid is lower than with IR nicotinic acid and it decreases substantially over time as tolerance develops. To date, there has been no clinically significant hepatotoxicity observed with PR nicotinic acid. Therefore, once-daily PR nicotinic acid appears to maximise the potential benefits of nicotinic acid, while minimising any historical tolerability or safety concerns.