Niaspan®: creating a new concept for raising HDL-cholesterol
Kos Pharmaceuticals Inc., Miami, FL, USA
* Corresponding author: 2200 North Commerce Parkway, Suite 300 Weston, FL 33326-3258, USA. Tel: +1 954 331 3730; fax: +1 954 331 3892. E-mail address: mmcgovern{at}kospharm.com
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Abstract |
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Low high-density lipoprotein (HDL)-cholesterol is associated with increased cardiovascular risk and often persists despite treatment with a statin. Nicotinic acid is the most effective agent available for correcting low HDL-cholesterol, but tolerability concerns have limited its use in the past. Niaspan® is a new, once-daily, prolonged-release formulation of nicotinic acid, which provides equivalent efficacy on the lipid profile to the immediate-release formulation. Treatment with Niaspan, alone or combined with a statin, is associated with marked improvements on HDL-cholesterol. Useful additional reductions in triglycerides and low density lipoprotein-cholesterol also occur when Niaspan is added to statin therapy. Analysis of lipid subprofiles shows that Niaspan treatment induces a shift from small, dense, highly atherogenic lipoproteins to a less atherogenic lipid profile, which is characterized by larger, more buoyant lipoprotein particles. The tolerability profile of Niaspan is superior to that of immediate-release nicotinic acid, with a significantly reduced frequency of flushing, and an incidence of hepatotoxicity or muscle side-effects similar to that of a statin. This beneficial therapeutic profile is also observed among patients with type 2 diabetes or the metabolic syndrome, with minimal impact on glycaemic control. Niaspan provides a practical new approach to the correction of low HDL-cholesterol in everyday clinical practice.
Key Words: Nicotinic acid • Cholesterol • Lipid profiles • Cardiovascular risk • HMG-CoA reductase inhibitors • Dyslipidaemia • Niaspan®
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Introduction |
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TopAbstractIntroductionEffects of Niaspan on...DiscussionConclusionsReferences |
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Low high-density lipoprotein (HDL)-cholesterol is an independent risk factor for adverse cardiovascular outcomes. Treatment with HMG-CoA reductase inhibitors (statins) exerts relatively little effect on this parameter, and low HDL-cholesterol often persists despite statin treatment. The use of additional interventions designed to increase HDL-cholesterol levels is, therefore, often appropriate for the reduction of overall cardiovascular risk. Nicotinic acid (niacin) is the most effective agent currently available for clinical use for increasing levels of HDL-cholesterol. Well-designed, double-blind, randomized studies, such as the Coronary Drug Project and the HDL Atherosclerosis Treatment Study (HATS), have demonstrated significant improvements in cardiovascular outcomes in nicotinic acid treated patients.
Tolerability issues, particularly flushing and/or hepatotoxicity, have tended to limit the clinical use of older, immediate-release, or sustained-release formulations of nicotinic acid. Niaspan® is a new, prolonged-release formulation of nicotinic acid, which is as effective as the immediate-release formulation but has a tolerability profile superior to immediate-release or older, sustained-release nicotinic acid preparations. Niaspan contains nicotinic acid within a time-release system (the Hydrogel Programmed Release Formulation).1 Nicotinic acid is released in a controlled manner from the gel matrix of the Niaspan tablet as hydration occurs after the tablet is swallowed. At least 60–76% of nicotinic acid from the Niaspan tablet is absorbed, with a time to peak plasma nicotinic acid concentration of 4–5 h.1
This review summarizes the therapeutic profile of nicotinic acid, with and without additional treatment with a HMG-CoA reductase inhibitor (statin) in patients with dyslipidaemia.
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Effects of Niaspan on the lipid profile |
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Niaspan monotherapy
Three multi-centre, double-blind, placebo-controlled studies have addressed the effects of Niaspan, given as monotherapy, in patients with primary hyperlipoproteinaemia despite treatment with diet. One study evaluated the effects of Niaspan at doses between 500 and 3000 mg, with the dose increased by 500 mg at 4-week intervals.2 The second study evaluated Niaspan at doses of 1000 and 2000 mg over 12 weeks of treatment,3 whereas the third was a 16 week study designed to compare the effects of Niaspan 1500 mg on lipids with various doses of immediate-release nicotinic acid.4
The effects on lipid parameters pooled from these three studies are shown in Figure 1.5 The mean baseline HDL-cholesterol levels of the patient populations of these studies ranged from 1.1 to 1.2 mmol/L (43–45 mg/dL), and thus were not low, on average, according to the current guidelines for the management of dyslipidaemia.6,7 Nevertheless, treatment with Niaspan markedly and dose-dependently increased HDL-cholesterol, with the magnitude of the effect tending to reach a plateau above the recommended daily dose of 2000 mg/day. Dose-related decreases in low density lipoprotein (LDL)-cholesterol, total cholesterol, and the atherogenic lipoprotein Lp(a) were also observed over the therapeutic dose range of Niaspan.
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The efficacy of Niaspan, given as a single daily dose of 1500 mg, was compared with that of immediate-release nicotinic acid, given three times daily at a total daily dose of 1500 mg, during 8 weeks of double-blind treatment in 223 patients with primary dyslipidaemia.4 Niaspan was as effective as the immediate-release preparation in improving HDL-cholesterol, LDL-cholesterol, triglycerides, and Lp(a) (Figure 2).
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Niaspan combined with a statin
A retrospective analysis conducted at a major university health centre in the USA evaluated the effects on the lipid profile of adding Niaspan to the regimens of patients already receiving a statin.8 Patients had been prescribed Niaspan because they had either elevated LDL-cholesterol despite the statin, or had low HDL-cholesterol, with or without elevated triglycerides. All clinical charts of patients taking Niaspan and a statin were reviewed (n=184). Of these, 66 subjects, who had been on a stable dose of a statin for 6 weeks or more, had received Niaspan at a dose of 1000 mg (all 66 patients) or 2000 mg (28/66 patients), and who had undergone lipid profiling before and after prescription of Niaspan, were included in the analysis.
The addition of Niaspan to the regimen resulted in marked improvements in HDL-cholesterol at both doses of Niaspan (Figure 3). Dose-related reductions in LDL-cholesterol and total cholesterol were also observed, whereas the substantial additional reduction in triglycerides following Niaspan treatment was effectively maximal at 1000 mg. Larger effects on HDL-cholesterol were observed in a subset of patients with low HDL-cholesterol at baseline [<1.0 mmol/L (<40 mg/dL), n=35], compared with the overall population (mean increases in HDL-cholesterol of 30 vs. 23%, respectively, for Niaspan 1000 mg). Similarly, effects on LDL-cholesterol were larger in patients with LDL-cholesterol >3.4 mmol/L (>130 mg/dL), with mean reductions from baseline of 19 and 8%, respectively, for Niaspan 1000 mg.
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These data, gained in the real-life clinical setting, confirm results of randomized evaluations of Niaspan combined with a statin in patients with dyslipidaemia.9,10 One double-blind, placebo-controlled study evaluated all reasonable combinations of Niaspan and lovastatin in a total of 164 patients with hyperlipidaemia. Patients received lovastatin (titrated from 10 to 20 to 40 mg at 4 week intervals), Niaspan, administered at doses of 500, 1000, 1500, 2000, or 2500 mg, with the dosage increased sequentially at 4-week intervals, or the combination of Niaspan and lovastatin, titrated similarly. Dose-related improvements in HDL-cholesterol and LDL-cholesterol were observed with Niaspan at each lovastatin dose. The maximum recommended dose of Niaspan (2000 mg) combined with lovastatin 40 mg increased HDL-cholesterol by 29%, compared with 9.5% with lovastatin 40 mg alone. Similarly, average decreases in LDL-cholesterol were larger with Niaspan 2000 mg/lovastatin 40 mg (–45.6%) than with lovastatin 40 mg alone (–24.4%).
A further 16 week, open-label trial evaluated two Niaspan–lovastatin combinations in patients with low HDL-cholesterol [<1.2 mmol/L (<45 mg/dL) in men or <1.3 mmol/L (<50 mg/dL) in women] and elevated LDL-C [cut-off values ranging from 3.4 to 4.1 mmol/L (130–160 mg/dL), depending on the patients' cardiovascular risk factor profiles].11 Patients were randomized to one of four treatment groups, one of which involved treatment with Niaspan 1000 mg/lovastatin 40 mg for 16 weeks and the other three of which involved escalating doses of Niaspan and/or comparators to achieve final doses at 16 weeks of Niaspan 2000 mg/lovastatin 40 mg, atorvastatin 40 mg, or simvastatin 40 mg.
At week 16, the Niaspan 1000 mg/lovastatin 40 mg and Niaspan 2000 mg/lovastatin 40 mg combinations increased HDL-cholesterol by 17 and 32%, respectively. Both increases were significantly superior (P<0.05) to those observed for atorvastatin 40 mg (+6%) and simvastatin (+7%). Changes from baseline in triglycerides with the Niaspan-based combinations (–29 and –49%), were significantly superior (P<0.05) to that seen with simvastatin (–19%), whereas atorvastatin reduced this parameter by 31% (P<0.05 vs. simvastatin). LDL-cholesterol was reduced by 39–49% across the four groups, with the largest change in the atorvastatin group (P<0.05). However, the Niaspan 1000 mg/lovastatin 40 mg dose produced equal reductions in LDL-cholesterol (–38 to –42%) and apolipoprotein B (apoB) (–33 to –36%) as 10 and 20 mg of atorvastatin. Finally, Lp(a) was reduced by 19 and 21% in the Niaspan–lovastatin arms, compared with no change in the atorvastatin group and a reduction of 2% in the simvastatin group (P<0.05 for each statin vs. either combination group).
Long-term efficacy of Niaspan
A 96 week, open-label, multi-centre study evaluated the effects of Niaspan, given as monotherapy or with a statin, on lipid profiles in a large cohort of patients with primary hypercholesterolaemia.12,13 Patients had been enrolled in previous shorter-term studies or had participated in a qualification trial in which they received only placebo. The primary efficacy endpoints were per cent changes from baseline in LDL-cholesterol and apoB. Changes in HDL-cholesterol, triglycerides, and Lp(a) were included among secondary efficacy endpoints. Niaspan was started at a dose of 375 mg (once daily, at bedtime after a low-fat snack) and titrated over a 4 week period to 1000 mg, and thereafter to either 2000 or 3000 mg at 4 week intervals, depending on the therapeutic response. Additional treatment with a statin or bile acid sequestrant was allowed if the final Niaspan dose was 
2000 mg.
The primary analysis included 723 patients, of whom 
70% (n=517) received treatment with Niaspan alone, with the remainder receiving additional treatment with a statin or a bile acid sequestrant. The median daily Niaspan dose for all patients was 2000 mg. Figure 4(A) shows data from patients treated for 48 and 96 weeks. Niaspan alone significantly improved HDL-cholesterol from baseline at 48 and 96 weeks (P<0.001).12 ApoB also improved significantly at either time point (by 16 and 17%, respectively, P<0.001). LDL-cholesterol, total cholesterol, triglycerides, and Lp(a) also improved significantly after 48 weeks of Niaspan treatment (P<0.001). Changes in these parameters at 96 weeks were similar to those observed at 48 weeks.
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Data at the 96 week time point on HDL-cholesterol, LDL-cholesterol, and triglycerides are available from 122 patients who received Niaspan in combination with a statin (Figure 4B).13 The effects of Niaspan combined with a statin on HDL-cholesterol were similar to those observed in patients receiving Niaspan alone (Figure 4B). The combination of Niaspan with a statin induced clinically significant additional reductions of LDL-cholesterol and triglycerides when compared with Niaspan alone (Figure 4B). The magnitudes of effects on HDL-cholesterol, LDL-cholesterol, and triglycerides were similar when Niaspan was combined with any statin (27, –35, and –36%, respectively, n=122) or the major statins, pravastatin (26, –35, and –34%, respectively, n=68), simvastatin (31, –36, and –39%, respectively, n=28), or lovastatin (24, –33, –33%, respectively, n=8).
Effects of Niaspan on lipid subprofiles
Subjects with insulin resistance, for example patients with the metabolic syndrome or type 2 diabetes, often present with a distinctive and highly atherogenic lipid profile characterized by low HDL-cholesterol, elevated triglycerides, and a shift towards small, dense HDL, and LDL particles.14,15 Treatments which reverse this shift and produce larger, more buoyant lipoproteins are therefore likely to be anti-atherogenic.
The effects of Niaspan on lipid subprofiles were evaluated in a sample of 60 patients previously enrolled in a 12 week double-blind, randomized trial.3,16 This study used the nuclear magnetic resonance method to subclassify lipoprotein particles. H5 is the largest, most cardioprotective form of HDL-cholesterol identified by this method, whereas H1 is the smallest and least cardioprotective HDL species (see Bays and McGovern17 for a review of this area). LDL particles range from L1 (smallest, most atherogenic) to L3 (largest, least atherogenic). These also correspond to ‘Pattern B’ and ‘Pattern A’ LDL phenotype, respectively. Treatment with Niaspan 1000 or 2000 mg preferentially increased larger, more buoyant, and more cardioprotective H4 and H5 HDL (Figure 5A). Similarly, levels of L1, the most atherogenic form of LDL, were markedly and preferentially reduced (Figure 5B).
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These results on HDL subclass distribution have been confirmed in multiple, other Niaspan studies in which the major HDL subpopulations were measured by the classical double precipitation method using magnesium dextran sulfate and classified as HDL2 or HDL3. For example, in the Niaspan dose-escalation study, in which the dosage of Niaspan was increased by 500 mg increments every 4 weeks,2 treatment with Niaspan 1000 and 2000 mg increased the more cardioprotective HDL2 from baseline by 38 and 69%, respectively, compared with 8 and 19%, respectively, on placebo (P<0.05 for each comparison). Finally, the study comparing Niaspan with immediate-release nicotinic acid, described earlier, showed that both formulations were effective in increasing HDL2, as assessed by this method.4
Similar results have been obtained when Niaspan was combined with a statin. The effects of a Niaspan–lovastatin combination tablet on lipid subprofiles were evaluated in 315 patients with low HDL-cholesterol [<1.2 mmol/L (<45 mg/dL) in men and <1.3 mmol/L (<50 mg/dL) in women].11,17 Niaspan 1000 or 2000 mg combined with lovastatin 40 mg preferentially increased levels of the large, cardioprotective subspecies of HDL, HDL2, by 113 and 189% of the baseline value, respectively, compared with increases of 30% for atorvastatin 40 mg and 42% for simvastatin 40 mg (P<0.05 for either Niaspan-based combination vs. either statin).11 Levels of smaller, less cardioprotective, HDL3 were affected similarly by Niaspan 1000 mg+lovastatin 40 mg (+8%), Niaspan 2000 mg+lovastatin 40 mg (+15%), atorvastatin 40 mg (+4%), or simvastatin 40 mg (+4%), though effects on the combination groups achieved statistical significance relative to the statin monotherapy groups (P<0.05). A further analysis of these data using yet another separation method, segmented gradient gel electrophoresis,17 showed that Niaspan 2000 mg+lovastatin 40 mg increased levels of the largest subspecies of HDL, (known as HDL2b by this method), by 42% from baseline, compared with 17% for atorvastatin and 5% for simvastatin (P<0.001 for each).17
LDL subprofiles also improved in this study. At baseline, 52% of patients in the Niaspan 2000 mg+lovastatin 40 mg group had the small, atherogenic ‘Pattern B’ LDL phenotype, as determined by gradient gel electrophoresis, compared with 57% of the atorvastatin group and 61% of the simvastatin group. After 16 weeks of treatment, only 10% of the combination group still had this atherogenic phenotype (an 81% reduction) when compared with 51% for atorvastatin (P<0.01) and 46% for simvastatin (P<0.001).
Niaspan in patients with type 2 diabetes
Dyslipidaemia, particularly low HDL-cholesterol, is an important driver of adverse outcomes in type 2 diabetes, as described earlier. However, an overview of the effects of Niaspan in this population is provided subsequently, as this subject is covered in detail in the accompanying paper by Dr Charles Reasner. The effects of Niaspan on glycaemia in type 2 diabetes are discussed separately in the section on safety and tolerability.
The effects of Niaspan on the lipid profile in patients with type 2 diabetes are essentially similar to those in non-diabetic populations. For example, a 16 week, randomized, double-blind, placebo-controlled study, the Assessment of Diabetes Control and EValuation of the Efficacy of Niaspan Trial (ADVENT), evaluated Niaspan at doses of 1000 or 1500 mg in 146 patients with type 2 diabetes.18 The inclusion criteria relating to lipid profiles included a requirement to have either low HDL-cholesterol or elevated triglycerides, so that the mean HDL-cholesterol at baseline was 1.0–1.1 mmol/L (39–41 mg/dL) in the Niaspan groups. Treatment with Niaspan 1000 or 1500 mg markedly, dose-dependently, and significantly (P<0.05 vs. placebo) increased HDL-cholesterol from baseline, by 19 [0.2 mmol/L (8 mg/dL)] and 24% [0.3 mmol/L (11 mg/dL)], respectively. Niaspan 1500 mg also reduced triglycerides and LDL-cholesterol significantly (P<0.05) when compared with placebo at 16 weeks.
A 20 week, double-blind, randomized evaluation demonstrated the efficacy of Niaspan (1000 or 1500 mg) combined with lovastatin 40 mg on lipid profiles in patients with type 2 diabetes and dyslipidaemia, defined as HDL-cholesterol 1.0 mmol/L (40 mg/dL) in men or 1.3 mmol/L (50 mg/dL) in women, together with triglycerides 
1.7 mmol/L (150 mg/dL).19 Niaspan 1500 mg in combination with lovastatin 40 mg increased HDL-cholesterol significantly (P<0.05) vs. the comparator agent, fenofibrate (24–26% vs. 12–15%, respectively), whereas both doses of Niaspan 1000 and 1500 mg in combination with lovastatin 40 mg also reduced LDL-cholesterol, non-HDL-cholesterol, and the atherogenic lipoprotein, Lp(a), significantly when compared with fenofibrate (P<0.05).
A retrospective analysis of the effects of up to 4 months of treatment with Niaspan in 53 type 2 diabetes patients confirms the beneficial effects of Niaspan on the effects on overall lipid profiles, and lipid subprofiles, in this population.20 In patients with low HDL2 (defined as <40% of total HDL-cholesterol) at baseline, Niaspan increased total HDL-cholesterol from 1.0 mmol/L (38 mg/dL) to 1.4 mmol/L (54 mg/dL), with identical effects observed when Niaspan was combined with atorvastatin. Total HDL-cholesterol was essentially unchanged with atorvastatin (P<0.001–0.005 vs. Niaspan-containing groups). HDL2-cholesterol mass increased from 0.15 to 0.28 mmol/L (6–11 mg/dL) with Niaspan alone (P<0.0001) and with Niaspan+atorvastatin. These effects were significantly superior to the increase in HDL2-cholesterol mass from 0.15 to 0.23 mmol/L (6–9 mg/dL) with atorvastatin alone (P<0.03–0.04). Thus, the effects of both Niaspan monotherapy and the Niaspan-based combination were significantly greater compared with atorvastatin alone, both for total HDL-cholesterol and for HDL2-cholesterol mass.
Efficacy of Niaspan in the metabolic syndrome
Subjects with the metabolic syndrome are also frequently insulin resistant, with a spectrum of lipid abnormalities comparable with those of the type 2 diabetic population.21 Accordingly, the effects of Niaspan 2000 mg plus lovastatin 40 mg have been evaluated in 756 patients with (n=347) or without (n=409) the metabolic syndrome.22 Marked improvements were observed, irrespective of the presence or absence of the metabolic syndrome, in HDL-cholesterol (average change from baseline of +36 vs. +32%, respectively), triglycerides (–47 and –32%), Lp(a) (–22 and –26%), and LDL-cholesterol (–42 and –45%).
Safety and tolerability of Niaspan
The principal tolerability issues associated with Niaspan are flushing and elevated liver enzymes. The incidence of flushing with Niaspan has been studied in short-term trials (up to 6 months duration of treatment) and during long-term treatment (up to 12 months).5 In one 4 month study (Niaspan vs. immediate-release nicotinic acid), the frequency of flushing was, on average, reduced by almost 80% with Niaspan when compared with the immediate-release formulation of nicotinic acid (Figure 6). The long-term study also showed that the frequency of flushing decreased over time (Figure 6), with an observed frequency at the end of the study which was less than half of that observed during the first 3 months of treatment. In all Niaspan clinical trials, the rate of discontinuation for flushing has been 6%.
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Earlier sustained-release formulations of this agent have also been associated with hepatotoxicity, sometimes severe.23–25 In long-term evaluations of Niaspan monotherapy (n=517, average treatment duration of 96 weeks), or Niaspan combined with a statin (n=165, average treatment duration of 56 weeks), <1% of patients reported circulating AST (GOT) or ALT (GPT) levels more than three times the upper limit of normal.12,13 These figures have been confirmed in experience with more than 8000 patients receiving Niaspan, alone or in combination with a statin, in clinical research trials. The risk of hepatotoxicity with Niaspan is therefore minimal and similar to that of a statin.
These adverse events arise through the metabolism of nicotinic acid through two biochemical pathways.25 The metabolism of nicotinic acid via a high affinity, but low capacity, non-conjugative biochemical pathway, which leads ultimately to the formation of nicotinamide, is responsible for hepatotoxicity. Elimination of nicotinic acid via a second, relatively high capacity, but low affinity, conjugative pathway leads to flushing. An oral dose of immediate-release nicotinic acid rapidly saturates the first system, and more of the plasma load of drug is metabolized via the conjugative system, leading to the high incidence of flushing, as described earlier. Earlier attempts to produce sustained-release formulations of nicotinic acid increased the proportion of nicotinic acid metabolized by the nicotinamide pathway, accounting for the unacceptable level of hepatic toxicity experienced with these agents.24,25 The prolonged-release formulation of Niaspan, with rates of absorption intermediate between the earlier sustained-release and immediate-release formulations, along with once-daily dosing, provides the optimum pharmacokinetic profile for minimizing both flushing and liver toxicity.
Rhabdomyolysis is a rare, but potentially severe, side-effect of statins, when these agents are given as monotherapy or combined with fibrates or, possibly, nicotinic acid.26,27 Extensive clinical use of Niaspan in the USA (more than 12 million prescriptions) has revealed that combining Niaspan with a statin incurs no increased risk of muscle side-effects when compared with that expected with a statin alone.
Increases in blood glucose following the administration of nicotinic acid have previously hindered its use in patients with type 2 diabetes, despite the frequent need of this population for HDL-cholesterol raising therapy. Randomized trials with Niaspan in patients with type 2 diabetes have shown that increases in HbA1C or fasting plasma glucose are minimal and easily corrected by adjustments of antidiabetic therapy in patients receiving Niaspan alone18 or combined with a statin.19 Concerns over hyperglycaemia should not deter the administration of Niaspan for correction of low HDL-cholesterol in a type 2 diabetic patient.
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Discussion |
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TopAbstractIntroductionEffects of Niaspan on...DiscussionConclusionsReferences |
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Nicotinic acid is the most effective agent available for correcting low HDL-cholesterol, which is an independent risk factor for adverse cardiovascular outcomes. Niaspan is as effective as immediate-release nicotinic acid in increasing levels of HDL-cholesterol and also provides useful improvements in triglycerides and LDL-cholesterol. Lipid subprofiles are improved after Niaspan treatment, with a shift towards larger, more cardioprotective HDL2 particles, and larger, less atherogenic LDL particles. These benefits are preserved when Niaspan is combined with a statin, an important observation as statins, given alone or with ezetimibe, provide little improvement in HDL-cholesterol.9,11,28–30 Overall, the effects of Niaspan on the lipid profile are consistent with a greater overall reduction in cardiovascular risk than treatment with a statin alone.
In addition, nicotinic acid is the only lipid-modifying agent consistently proven to reduce levels of Lp(a). Elevated levels of this atherogenic lipoprotein appear to promote the pro-inflammatory reactions underlying atherogenesis31 and were significantly associated with an increased risk of myocardial infarction and other adverse cardiovascular outcomes in the Framingham study.32 Importantly, the efficacy of Niaspan is not blunted by the presence of insulin resistance, as demonstrated by studies in patients with type 2 diabetes or the metabolic syndrome.
The safety and tolerability of Niaspan are superior to those of earlier formulations of nicotinic acid. Niaspan is associated with a markedly reduced incidence of flushing, and minimal potential for elevated liver enzymes, due to the optimized release of nicotinic acid from the Niaspan tablet over time and once-daily dosing. In addition, Niaspan is well tolerated with regard to side-effects in muscle, when given alone or combined with a statin.
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Conclusions |
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TopAbstractIntroductionEffects of Niaspan on...DiscussionConclusionsReferences |
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Correcting low HDL-cholesterol is an urgent clinical priority for the prevention of cardiovascular events. Niaspan provides the full efficacy of immediate-release nicotinic acid in improving HDL-cholesterol and other lipid parameters, together with superior tolerability and safety profiles. This is true both for patients with primary dyslipidaemia and patients with dyslipidaemia secondary to type 2 diabetes or the metabolic syndrome. The development of Niaspan provides a practical approach for raising HDL-cholesterol in routine clinical care.
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References |
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