Niacin as a component of combination therapy for dyslipidemia

Dyslipidemia is one of the most important modifiable risk factors for coronary disease. Despite the availability of highly effective lipid-modifying agents, many patients still do not reach lipid targets established by national guidelines. Niacin has been known to be an effective treatment of dyslipidemia for almost half a century. Niacin substantially increases high-density lipoprotein cholesterol (HDL-C) levels while lowering levels of low-density lipoprotein cholesterol (LDL-C), triglycerides, and lipoprotein(a). In addition, niacin converts small LDL particles into more buoyant, less atherogenic LDL particles. Combined with other agents, niacin offers an important treatment option for patients with dyslipidemia. In particular, niacin complements LDL-C-lowering drugs; it is the most effective agent available for increasing HDL-C levels while lowering levels of LDL-C and triglycerides and improving other lipid risk factors such as lipoprotein(a). Combining niacin with statins or bile acid sequestrant therapy is safe and effective for improving lipid levels and decreasing coronary risk. Differences in niacin formulations dictate tolerability profiles and should be considered when selecting niacin as part of lipid therapy. Furthermore, adverse effects on glucose and insulin sensitivity should be considered when selecting candidates for niacin therapy. Adding niacin to lipid-lowering regimens is a valuable option for physicians treating patients with dyslipidemia and should be considered in appropriate patients.     

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

Background: Improving lipids beyond low‐density lipoprotein cholesterol (LDL‐C) lowering with statin monotherapy may further reduce cardiovascular risk. Niacin has complementary lipid‐modifying efficacy to statins and cardiovascular benefit, but is underutilised because of flushing, mediated primarily by prostaglandin D₂ (PGD₂). Laropiprant (LRPT), a PGD₂ receptor (DP1) antagonist that reduces niacin‐induced flushing has been combined with extended‐release niacin (ERN) into a fixed‐dose tablet. Methods and results: Dyslipidaemic patients were randomised to ERN/LRPT 1 g (n = 800), ERN 1 g (n = 543) or placebo (n = 270) for 4 weeks. Doses were doubled (2 tablets/day; i.e. 2 g for active treatments) for 20 weeks. ERN/LRPT 2 g produced significant changes vs. placebo in LDL‐C (?18.4%), high‐density lipoprotein cholesterol (HDL‐C; 20.0%), LDL‐C:HDL‐C (?31.2%), non‐HDL‐C (?19.8%), triglycerides (TG; ?25.8%), apolipoprotein (Apo) B (?18.8%), Apo A‐I (6.9%), total cholesterol (TC; ?8.5%), TC:HDL‐C (?23.1%) and lipoprotein(a) (?20.8%) across weeks 12–24. ERN/LRPT produced significantly less flushing than ERN during initiation (week 1) and maintenance (weeks 2–24) for all prespecified flushing end‐points (incidence, intensity and discontinuation because of flushing). Except for flushing, ERN/LRPT had a safety/tolerability profile comparable with ERN. Conclusion: Extended‐release niacin/LRPT 2 g produced significant, durable improvements in multiple lipid/lipoprotein parameters. The improved tolerability of ERN/LRPT supports a simplified 1 g→2 g dosing regimen of niacin, a therapy proven to reduce cardiovascular risk.     

The effects of extended-release niacin on carotid intimal media thickness, endothelial function and inflammatory markers in patients with the metabolic syndrome

BACKGROUND: Niacin is an agent that significantly increases high-density lipoprotein cholesterol (HDL-C), but its effects on surrogate markers of atherosclerosis and inflammatory markers are less clear. We studied the effects of niacin on carotid intimal media thickness (IMT), brachial artery reactivity as well as markers of inflammation and the metabolic profile of patients with metabolic syndrome. METHODS AND RESULTS: Fifty patients with the metabolic syndrome (Adult Treatment Panel (ATP) III criteria) were randomised to either extended-release niacin (1000 mg/day) or placebo. After 52 weeks of treatment, there was a change of carotid IMT of +0.009 +/- 0.003 mm in the placebo group and -0.005 +/- 0.002 mm in the niacin group (p = 0.021 between groups). Endothelial function improved by 22% in the group treated with niacin (p < 0.001), whereas no significant changes were seen in the placebo group. High sensitivity C-reactive protein decreased by 20% in the group treated with niacin for 52 weeks (p = 0.013). Niacin increased HDL-C (p < 0.001) and decreased low-density lipoprotein cholesterol and triglycerides (p < 0.001) significantly, and there were no adverse effects on fasting glucose levels after 52 weeks of treatment. CONCLUSION: Extended-release niacin therapy effects a regression in carotid intimal medial thickness and improvement in metabolic parameters (increased HDL and reduced triglycerides). Furthermore, extended-release niacin may demonstrate an anti-atherogenic effect in the metabolic syndrome by improving endothelial function and decreasing vascular inflammation.     

Statins,fibrates, nicotinic acid,cholesterol absorption inhibitors,anion‐exchange resins,omega‐3 fatty acids: which drugs for which patients?

Classes of lipid lowering drugs differ strongly with respect to the types of lipids or lipoproteins they predominantly affect. Statins inhibit the de-novo synthesis of cholesterol. Consequently, the liver produces less VLDL, and the serum concentration primarily of LDL cholesterol (but, to a lesser extent, also of triglycerides) is lowered. Further, statins somewhat increase HDL cholesterol. There is abundant evidence that statins lower the rate of cardiovascular events. Cardiovascular risk reduction is the better, the lower the LDL cholesterol values achieved with statin therapy are. Some evidence is available that anion exchange resins which also decrease LDL cholesterol decrease vascular risk, too. This is not the case for the ezetimibe, which strongly lowers LDL cholesterol: its potential to decrease vascular risk remains to be proven. In contrast evidence for cardiovascular risk reduction through the mainly triglyceride lowering fibrates as well as for niacin is available. Niacin is the most potent HDL increasing drug currently available and besides increasing HDL cholesterol efficaciously lowers triglycerides and LDL cholesterol. Large ongoing trials address the decisive question whether treatment with fibrates and niacin provides additional cardiovascular risk reduction when given in addition to statin treatment.     

Niacin-a critical component to the management of atherosclerosis: contemporary management of dyslipidemia to prevent, reduce, or reverse atherosclerotic cardiovascular disease

Niacin (nicotinic acid) is the most effective agent for raising high-density lipoprotein cholesterol levels and can improve the entire lipid panel in patients with dyslipidemia. Niacin-containing regimens are among the few treatments studied for dyslipidemia that have both elicited significant reductions in atherosclerotic progression (by angiography or imaging) and also significantly reduced (by approximately 90% vs control) the incidence of cardiovascular events in a single clinical trial. However, cutaneous flushing-an uncomfortable but typically transient adverse effect of niacin-often results in patient nonadherence with this potentially life-saving therapy. Effective counseling regarding the highly favorable benefit-risk ratio for niacin and management strategies such as careful dose escalation, follow-up monitoring, regimen adjustments, and the use of treatment adjuncts (eg, aspirin) can improve patient adherence with niacin therapy. Clinicians are uniquely positioned to provide such counseling to appropriate patients for niacin treatment and hence encourage wider use of this important and necessary cardioprotective medication.     

Opening a new lipid "apo-thecary": incorporating apolipoproteins as potential risk factors and treatment targets to reduce cardiovascular risk

Statins (3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors) represent the cornerstone of drug therapy to reduce low-density lipoprotein (LDL) cholesterol and cardiovascular risk. However, even optimal statin management of LDL cholesterol leaves many patients with residual cardiovascular risk, in part because statins are more effective in reducing LDL cholesterol than apolipoprotein B (Apo B). Apo B may be a better marker of atherogenic risk than LDL cholesterol because Apo B measures the total number of all atherogenic particles (total atherosclerotic burden), including LDL, very low-density lipoprotein, intermediate-density lipoprotein, remnant lipoproteins, and lipoprotein(a). To determine whether Apo B is a better indicator of baseline cardiovascular risk and residual risk after lipid therapy compared with LDL cholesterol, a MEDLINE search of the literature published in English from January 1, 1975, through December 1, 2010, was conducted. On the basis of data from most population studies, elevated Apo B was more strongly associated with incident coronary heart disease than similarly elevated LDL cholesterol. Apo B was also a superior benchmark (vs LDL cholesterol) of statins' cardioprotective efficacy in both primary-prevention and secondary-prevention trials. To minimize cardiovascular risk among persons with hypercholesterolemia or dyslipidemia, the best available evidence suggests that intensive therapy with statins should be initiated to achieve the lowest possible Apo B level (with adequate drug toleration) and then other therapies (eg, niacin, bile acid resins, ezetimibe) added to potentiate these Apo B-lowering effects. In future consensus lipid-lowering treatment guidelines, Apo B should be considered as an index of residual risk, a potential parameter of treatment efficacy, and a treatment target to minimize risk of coronary heart disease.     

Extended-release niacin/laropiprant lipid-altering consistency across patient subgroups

Background: In patients with primary hypercholesterolemia or mixed dyslipidemia, extended‐release niacin/laropiprant (ERN/LRPT) improves key lipid parameters associated with increased atherosclerotic coronary heart disease (CHD) risk. Aim: This analysis examined data from four Phase III, randomised, double‐blind trials to determine the consistency of ERN/LRPT’s lipid‐altering efficacy among subgroups of patients. Methods: Data from four Phase III, randomised, double‐blind trials of ERN/LRPT were analysed to determine the consistency of ERN/LRPT’s lipid‐altering efficacy among subgroups of gender, race (white, non‐white), region (US, ex‐US), baseline age (< 65, ≥ 65 years), use of statin therapy, CHD risk status (low, multiple, high) and type of hyperlipidemia (primary hypercholesterolemia, mixed dyslipidemia), as well as across baseline low‐density lipoprotein cholesterol (LDL‐C), high‐density lipoprotein cholesterol (HDL‐C) and triglyceride (TG) levels. End‐points included the per cent change from baseline in LDL‐C, HDL‐C and TG levels. Consistency of the treatment effects on LDL‐C, HDL‐C and TG across subgroups was evaluated by examining treatment difference estimates with 95% confidence intervals. Results: Treatment with ERN/LRPT significantly improved LDL‐C, HDL‐C and TG levels compared with placebo/active comparator in each study cohort. These effects were generally consistent across all examined subgroups. Conclusion: Extended‐release niacin/laropiprant represents an effective therapeutic option for the treatment of dyslipidemia across a range of patient types.     

An open-label comparison of the effects of simvastatin and niacin alone and combined on the lipid profile and lipoprotein (a) level in an Indian population with dyslipidemia

Abstract

Background:

Patients with dyslipidemia often require the use of >1 lipid-altering agent to achieve the target levels recommended by the National Cholesterol Education Program Adult Treatment Panel III.

Objective:

The aim of this study was to compare the effects of simvastatin and niacin alone and combined on the lipid profile and lipoprotein (a) (Lp[a]) level in an Indian population with dyslipidemia.

Methods:

This 12-week, open-label, nonrandomized study was conducted at the Departments of Pharmacology and Medicine, Government Medical College, Amritsar (Punjab), India. Patients aged 30 to 70 years with dyslipidemia were eligible. Patients were assigned to 1 of 3 treatment groups. Group 1 received simvastatin 20 mg/d for 12 weeks. Group 2 received niacin at doses of 375 mg/d for 1 week, 500 mg/d for 1 week, and 500 mg BID for 10 weeks. Group 3 received simvastatin 10 mg/d plus niacin (375 mg for 1 week and 500 mg for 11 weeks). The lipid profile (low-density lipoprotein cholesterol [LDL-C], high-density lipoprotein cholesterol [HDL-C], total cholesterol [TC], and triglycerides [TG]) and Lp(a) were measured before the start of therapy and at 6 and 12 weeks of treatment. Percentage changes from baseline were calculated. Adverse effects (AEs) were recorded at weeks 6 and 12 and through spontaneous reporting.

Results:

Ninety patients were enrolled (50 men, 40 women; 30 patients per treatment group). In group 1, the mean (SD) percentage decrease in LDL-C level at 12 weeks was 42.79% (16.29%) (P < 0.05), but no significant change was seen in group 2 or 3. The mean (SD) percentage increases in HDL-C level were 18.43% (13.28%) and 20.82% (17.57%) in groups 2 and 3, respectively (both, P < 0.05), but no significant change was seen in group 1. TC levels decreased by a mean (SD) of 32.97% (13.66%) in group 1 (P < 0.05), but no significant change was seen in group 2 or 3. TG and Lp(a) levels did not change significantly in any of the 3 treatment groups. Flushing, myalgia, and dyspepsia were the most common AEs in patients receiving niacin.

Conclusions:

In this study in Indian patients with dyslipidemia, simvastatin-niacin combination therapy was associated with greater changes in lipid profile compared with either agent used alone. Niacin was also associated with greater changes in Lp(a) levels. AEs were less prevalent with combination therapy than with niacin alone.Key words: dyslipidemia, simvastatin, niacin, combination therapy     

Niacin-ER and lovastatin treatment of hypercholesterolemia and mixed dyslipidemia

OBJECTIVE: To review the currently available information on the once-daily combination of niacin extended-release (ER)/lovastatin in the treatment of patients with hypercholesterolemia and mixed dyslipidemia at high risk for cardiovascular events. DATA SOURCES: MEDLINE (1966-July 2002) was searched for primary and review articles. Data from the manufacturer were also included. STUDY SELECTION/DATA EXTRACTION: All articles and product labeling deemed relevant to the combination of niacin and statins (i.e., lovastatin) were included for review. English-language studies selected for inclusion were limited to those with human subjects. DATA SYNTHESIS: The Food and Drug Administration approved a new fixed-dose combination of niacin-ER/lovastatin, which is administered once daily. The efficacy and safety of the combined agent have been proven to be similar to either component used alone or in combination for management of hyperlipidemia and mixed dyslipidemia. CONCLUSIONS: Elevated low-density lipoprotein cholesterol (LDL-C) is independently associated with a higher risk for cardiovascular events. Lowering of elevated LDL-C concentrations with statin monotherapy may be insufficient in patients at high risk for cardiovascular events. In fact, consideration of elevated triglycerides (TGs) and/or low concentrations of high-density lipoprotein cholesterol (HDL-C) in patients with elevated LDL-C places them at greater risk. The addition of niacin may enhance or improve the lipid profile of those who require a further decrease of TGs and/or increase of HDL-C even after stable statin therapy. Niacin-ER offers efficacy similar to that of immediate-release niacin, but minimal myopathy and hepatotoxicity (compared with sustained-release niacin). Although no clinical outcomes are available, current evidence shows that the combination product offers adequate lowering of LDL-C and TGs and increasing HDL-C. The data suggest that therapy with the niacin-ER and lovastatin combination product is safe and does not increase the incidence of adverse effects.     

Impact of the new National Cholesterol Education Program (NCEP) guidelines on patient management

PURPOSE: To update nurse practitioners (NPs) on the latest National Cholesterol Education Program (NCEP) guidelines for the management of high blood cholesterol in adults. DATA SOURCES: The 2001 NCEP Adult Treatment Panel (ATP) III guidelines and supporting scientific reviews and reports of clinical trials related to the evidence upon which the guidelines are based. CONCLUSIONS: The many new features of the ATP III guidelines include an increased emphasis on the patient with multiple risk factors in order to identify appropriate candidates for primary prevention and on more stringent classifications of elevated lipid/lipoprotein levels. However, elevated levels of low-density lipoprotein (LDL) cholesterol continue to be the focus for both primary and secondary prevention, and 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins) are clearly the drugs of choice for decreasing LDL cholesterol in most patients. IMPLICATIONS FOR PRACTICE: Because NPs play key roles in optimizing treatment management, it is important that they become familiar with, and be prepared to help implement, these latest guidelines. By embracing the global risk assessment approach of ATP III and aggressively treating all at-risk patients, NPs can take a proactive role in helping to halt the progression of coronary heart disease and its consequences.     

Predictability of low-density lipoprotein levels during apheretic treatment of hypercholesterolemia

The efficiency and efficacy of low-density lipoprotein (LDL) apheresis performed with a dextran sulphate cellulose (DSC) regenerating unit were tested in five familial hypercholesterolaemic patients. LDL apheresis was repeated four times at both bi-weekly and weekly intervals, processing one plasma volume each time. The efficiency of the procedure (i.e., the extent of lipoprotein removal) was nearly identical with both schedules. Efficacy parameters, i.e., decreases of plasma total and LDL cholesterol (TC and LDL-C) and apo B, were highly correlated (r greater than 0.96) with preapheresis levels, allowing an accurate prediction of the absolute lipid removal in the single individual. Plasma triglycerides, high-density lipoprotein cholesterol, apo A-I and apo A-II recovered rather rapidly, reaching 91-96% of the pre-apheresis values in 48 hours; the recovery of TC, LDL-C and apo B was much slower, with a relatively rapid early phase (80% recovery after about 7 days) followed by a successive slower rise. This pattern was highly reproducible in the single patient, allowing the definition of a simple mathematical model for an accurate (error less than 20%) prediction of the individual process. Based on this model one can design the treatment schedule necessary to maintain lipid levels within the desired range in the single individual. The hypolipidaemic efficacy of DSC apheresis appears, otherwise, not to be dependent upon the procedure per se, but on other individual factors, e.g. the amount of removable lipoproteins and the rate of lipid recovery; both can be predicted with sufficient accuracy.     

A comparison of clinical outcome studies among cholesterol-lowering agents.

OBJECTIVE: To review and compare clinical trials of cholesterol-lowering agents that evaluated clinical end points as the primary outcome measure; specifically, to determine whether all agents that decrease cholesterol impact clinical outcomes similarly. DATA SOURCES: Primary articles were identified through a MEDLINE search (1966-February 2001) and through secondary sources. STUDY SELECTION AND DATA EXTRACTION: All of the articles identified from the data sources were evaluated. Articles that included clinical end points as the primary outcome measure were included in this review. DATA SYNTHESIS: Clinical trials were assessed according to study population (primary vs. secondary prevention of coronary artery disease), baseline and follow-up lipid profiles, and clinical outcome data. Both cardiac and noncardiac morbidity and mortality were evaluated. The differences in study populations, study methods, and changes in lipid values were compared and contrasted between trials to evaluate their effect on outcomes. CONCLUSIONS: Niacin and bile acid sequestrants should be considered as add-on therapy when therapeutic goals cannot be attained with a hydroxymethyl glutaryl-coenzyme A reductase inhibitor (stain). Estrogen therapy cannot be recommended solely for cardioprotection. Fibrates are most effective in patients with high baseline triglycerides, low baseline high-density lipoprotein cholesterol, and low to average low-density lipoprotein cholesterol (LDL). Statins are considered first line for the treatment of elevated LDL in both the primary and secondary prevention of coronary heart disease. They are well tolerated, have the strongest data to support their use, and have been shown to decrease total mortality.     

Management of hypertriglyceridemia

Hypertriglyceridemia is associated with an increased risk of cardiovascular events and acute pancreatitis. Along with lowering low-density lipoprotein cholesterol levels and raising high-density lipoprotein cholesterol levels, lowering triglyceride levels in high-risk patients (e.g., those with cardiovascular disease or diabetes) has been associated with decreased cardiovascular morbidity and mortality. Although the management of mixed dyslipidemia is controversial, treatment should focus primarily on lowering low-density lipoprotein cholesterol levels. Secondary goals should include lowering non-high-density lipoprotein cholesterol levels (calculated by subtracting high-density lipoprotein cholesterol from total cholesterol). If serum triglyceride levels are high, lowering these levels can be effective at reaching non-high-density lipoprotein cholesterol goals. Initially, patients with hypertriglyceridemia should be counseled about therapeutic lifestyle changes (e.g., healthy diet, regular exercise, tobacco-use cessation). Patients also should be screened for metabolic syndrome and other acquired or secondary causes. Patients with borderline-high serum triglyceride levels (i.e., 150 to 199 mg per dL [1.70 to 2.25 mmol per L]) and high serum triglyceride levels (i.e., 200 to 499 mg per dL [2.26 to 5.64 mmol per L]) require an overall cardiac risk assessment. Treatment of very high triglyceride levels (i.e., 500 mg per dL [5.65 mmol per L] or higher) is aimed at reducing the risk of acute pancreatitis. Statins, fibrates, niacin, and fish oil (alone or in various combinations) are effective when pharmacotherapy is indicated.     

The mechanism and mitigation of niacin‐induced flushing

Aims:  To summarise the metabolic responses to niacin that can lead to flushing and to critically evaluate flushing mitigation research. Methods and results:  This comprehensive review of the mechanism of action of niacin‐induced flushing critically evaluates research regarding flushing mitigating formulations and agents. Niacin induces flushing through dermal Langerhans cells where the activation of G protein‐coupled receptor 109A (GPR109A) increases arachidonic acid and prostaglandins, such as prostaglandin D₂ (PGD₂) and prostaglandin E₂ (PGE₂), subsequently activating prostaglandin D₂ receptor (DP₁), prostaglandin E₂ receptor (EP₂) and prostaglandin E receptor 4 (EP₄) in capillaries and causing cutaneous vasodilatation. Controlling niacin absorption rates, inhibiting prostaglandin production, or blocking DP₁, EP₂ and EP₄ receptors can inhibit flushing. Niacin extended‐release (NER) formulations have reduced flushing incidence, duration and severity relative to crystalline immediate‐release niacin with similar lipid efficacy. Non‐steroidal anti‐inflammatory drugs (NSAIDs), notably aspirin given 30 min before NER at bedtime, further reduce flushing. An antagonist to the DP₁ receptor (laropiprant) combined with an ER niacin formulation can reduce flushing; however, significant residual flushing occurs with clinically‐relevant dosages. Conclusions:  Niacin is an attractive option for treating dyslipidemic patients, and tolerance to niacin‐induced flushing develops rapidly. Healthcare professionals should particularly address flushing during niacin dose titration.     

Change in very low-, low-, and high-density lipoproteins during lipid lowering (bezafibrate) therapy: studies in type IIA and type IIb hyperlipoproteinaemia

The effects of lipid lowering therapy (bezafibrate) on plasma lipoproteins was investigated in twelve patients with familial hypercholesterolaemia (type IIA) and eight with familial combined hyperlipidaemia (type IIB). Bezafibrate caused a decrease of plasma cholesterol, plasma triglycerides, plasma apolipoprotein B, VLDL cholesterol and LDL cholesterol and an increase of HDL cholesterol. Post-heparin plasma lipoprotein and hepatic lipase activities increased in both groups (significant only in type IIB). Lipoprotein composition showed the following changes: Increased protein and phospholipids and decreased triglycerides and cholesteryl esters in VLDL. Decreased protein and triglycerides and increased free and esterified cholesterol in LDL. Decreased triglycerides and increased phospholipids in HDL. Cholesteryl ester to protein ratios decreased in VLDL and increased in LDL. The hydrated density of LDL (both groups) and of HDL3 (type IIB) decreased following bezafibrate therapy. These changes were in general similar to those observed in hypertriglyceridaemic patients and could be ascribed, at least in part, to the increase of plasma lipase activities and the decrease of lipid transfer reactions. Comparing the present data with that previously reported, it was found that bezafibrate caused decreased LDL cholesterol in types IIA and IIB but increased levels in type IV. This change was correlated with the initial plasma triglycerides (r = 0.74, P less than 0.0001) and initial plasma LDL cholesterol (r = 0.66, P less than 0.001). It is concluded that varied response of LDL to therapy reflects a complex interaction of metabolic events, including changing rates of VLDL conversion to LDL, lipoprotein compositional changes and effects of therapy on LDL degradation rates.     

Improved coronary risk assessment with electron beam computed tomography in an asymptomatic female with familial hypercholesterolemia

An asymptomatic 36-year-old woman had high cholesterol levels due to heterozygous familial hypercholesterolemia (FHC) and a family history of coronary artery disease (CAD) but no other risk factors. Exercise testing showed no signs of ischemia. Conventional drug therapy did not lower lipid levels adequately. However, low-density lipoprotein (LDL) apheresis, which effectively reduces cholesterol levels in patients with heterozygous FHC, was not indicated, according to current guidelines. Electron beam computed tomography demonstrated exceptionally high amounts of coronary calcium for the patient's age and sex. A subsequent coronary angiogram revealed advanced CAD, which justified the initiation of LDL apheresis to reduce her cholesterol levels. In patients with heterozygous FHC refractory to conventional lipid-lowering therapy, the presence of coronary calcium in the highest percentiles for age and sex (i.e., > 75th percentile) may warrant aggressive clinical management to improve prognosis, even if no symptoms or signs of ischemia are present.     

Efficacy and Tolerability of Low-dose Simvastatin and Niacin, Alone and in Combination, in Patients With Combined Hyperlipidemia: A Prospective Trial

BACKGROUND: Combination lipid-lowering therapy may be desirable in patients with elevated low-density lipoprotein cholesterol, high triglycerides, and low high-density lipoprotein cholesterol. This study was conducted to determine the lipid-lowering efficacy of the combination of low-dose simvastatin and niacin in patients with combined hyperlipidemia and low high-density lipoprotein cholesterol. METHODS AND RESULTS: In this multicenter, prospective, randomized trial, 180 patients with hypercholesterolemia and hypertriglyceridemia and/or low high-density lipoprotein cholesterol were randomized to combination simvastatin (10 mg/day) and niacin (0.75 g/day) or to either drug alone for 9 weeks. The dose of niacin was doubled (from 0.75 g/day to 1.5 g/day) in both the combination and niacin arms for the remaining 8 weeks. The combination of simvastatin, 10 mg/day, and niacin, 1.5 g/day, reduced total, low-density lipoprotein, and very low-density lipoprotein cholesterol and triglycerides by 24%, 29%, 45%, and 31%, respectively, while increasing high-density lipoprotein cholesterol by 31%. The addition of niacin to simvastatin did not enhance the low-density lipoprotein cholesterol by 31%. The addition of niacin to simvastatin did not enhance the low-density lipoprotein cholesterol-lowering effect of simvastatin; however, the combination was more effective than either monotherapy at raising high-density lipoprotein cholesterol and lowering very low-density lipoprotein cholesterol (P <.05). More patients discontinued treatment because of an adverse event in the niacin (P <.03) and combination groups (P =.06) than the simvastatin group. CONCLUSIONS: Treatment of patients with combined hyperlipidemia and/or low high-density lipoprotein with combination low-dose simvastatin and niacin resulted in large reductions in total, low-density lipoprotein, and very low-density lipoprotein cholesterol and increases in HDL cholesterol. Although the combination was well tolerated in the current trial, its safety needs to be evaluated in larger trials of longer duration.