Lipid-altering Drugs Research Articles

What's the deal with niacin development: is laropiprant add-on therapy a winning strategy to beat a straight flush?

Niacin is a B-complex vitamin used as a lipid-altering drug since the 1950s. Niacin improves multiple lipid parameters. Atherosclerotic coronary heart disease outcome studies support niacin's efficacy in reducing coronary heart disease events, either as monotherapy or when used in combination with other lipid-altering drugs. The most commonly reported reason for the lack of its more widespread clinical use is niacin-induced flushing. Laropiprant is a highly selective prostaglandin D2 receptor 1 antagonist that mitigates niacin-induced flushing. This review examines the history and provides a perspective regarding the extended-release niacin/laropiprant development program, which was designed to better allow patients to achieve a more therapeutic niacin dose of 2 g/day, without the need for titration. Ongoing coronary heart disease outcome studies will provide better insight as to the benefits of niacin in general, and the safety and efficacy of extended-release niacin/laropiprant specifically.

Do Age, Gender, and Race Affect the Efficacy of Ezetimibe Plus Atorvastatin vs. Doubling the Atorvastatin Dose in Moderately High and High CHD Risk Patients?

Synopsis: Age, gender, and race are factors that influence atherosclerotic coronary heart disease (CHD) risk, and may conceivably affect the efficacy of lipid-altering drugs.

Efficacy and Safety of ABT-335 (Fenofibric Acid) in Combination With Atorvastatin in Patients With Mixed Dyslipidemia

In patients with mixed dyslipidemia characterized by increased triglycerides (TG), decreased high-density lipoprotein (HDL) cholesterol, and increased low-density lipoprotein (LDL) cholesterol, monotherapy with lipid-altering drugs often fails to achieve all lipid targets. This multicenter, double-blind, active-controlled study evaluated ABT-335 (fenofibric acid) in combination with 2 doses of atorvastatin in patients with mixed dyslipidemia. A total of 613 patients with LDL cholesterol > or =130 mg/dl, TG > or =150 mg/dl, and HDL cholesterol <40 mg/dl for men and <50 mg/dl for women were randomly assigned to ABT-335 (135 mg), atorvastatin (20, 40, or 80 mg), or combination therapy (ABT-335 + atorvastatin 20 or 40 mg) and treated for 12 weeks. Combination therapy with ABT-335 + atorvastatin 20 mg resulted in significantly greater improvements in TG (-45.6% vs -16.5%) and HDL cholesterol (14.0% vs 6.3%) compared with atorvastatin 20 mg and LDL cholesterol (-33.7% vs -3.4%) compared with ABT-335. Similarly, significantly greater improvements were observed with ABT-335 + atorvastatin 40 mg in TG (-42.1% vs -23.2%) and HDL cholesterol (12.6% vs 5.3%) compared with atorvastatin 40 mg and LDL cholesterol (-35.4% vs -3.4%) compared with ABT-335 monotherapy. Combination therapy also improved multiple secondary variables. Combination therapy was generally well tolerated with a safety profile consistent with those of ABT-335 and atorvastatin monotherapies. No rhabdomyolysis was reported. In conclusion, ABT-335 + atorvastatin combination therapy resulted in more effective control of multiple lipid parameters than either monotherapy and may be an appropriate therapy for patients with mixed dyslipidemia.

Does nicotinic acid (niacin) lower blood pressure?

Nicotinic acid (niacin) is a well-established treatment for dyslipidaemia – an important cardiovascular disease (CVD) risk factor. However, niacin may also reduce blood pressure (BP), which is another important CVD risk factor. This review examines the limited publicly available data on niacin’s BP effects. Acute administration of immediate-release niacin may lower BP because of niacin’s acute vasodilatory effects. Although not always supported by clinical trial data, the package insert of a prescription, extended-release niacin describes niacin-induced acute hypotension. From a chronic standpoint, larger studies, such as the Coronary Drug Project, suggest that niacin may lower BP when administered over a longer period of time. Post hoc analyses of some of the more recent niacin clinical trials also support a more chronic, dose-dependent, BP-lowering effect of niacin. Because laropiprant [a prostaglandin D2 (PGD2) type 1 (DP1) receptor antagonist] does not attenuate niacin’s BP-lowering effects, it is unlikely that any chronic lowering of BP by niacin is due to dilation of dermal vessels through activation of the DP1 receptor by PGD2. Further research is warranted to evaluate the extent and mechanisms of niacin’s effects on BP.

The Safety of Niacin in the US Food and Drug Administration Adverse Event Reporting Database

Of currently approved drugs, niacin is the most effective in raising high-density lipoprotein cholesterol levels, either as monotherapy or in combination with other agents. The US Food and Drug Administration's (FDA) Adverse Event Reporting System provides 1 mechanism to evaluate the safety of niacin as it is used in common clinical practice. In this report, the authors review recent analyses of adverse events reported to the FDA demonstrating that the extended-release formulation of niacin (niacin-ER) has a significantly better safety profile compared with other niacin formulations and compares favorably with other commonly used lipid-altering drugs, including 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) and fibrates. In addition, analyses of FDA adverse event reports of the pill combining lovastatin and niacin-ER suggest that the safety of combination therapy with niacin-ER and a statin is comparable with the safety of each of the drugs alone. These analyses should encourage the use of niacin-ER in patients at high risk for cardiovascular disease, as recommended by current national guidelines for cardiovascular prevention.

Safety of Niacin and Simvastatin Combination Therapy

Niacin is the most potent lipid-altering agent for raising high-density lipoprotein (HDL) cholesterol levels. Niacin also lowers triglyceride (TG) levels, lowers low-density lipoprotein (LDL) cholesterol levels, and improves lipoprotein particle size and subclass distribution. Niacin's major adverse experience (AE) is flushing. Niacin may also increase glucose levels, liver enzymes, and uric acid levels and cause other AEs that may have clinical relevance in selected patients. Simvastatin is representative of the 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor (statin) class of lipid-altering drugs, which are the most effective agents for lowering LDL cholesterol levels and also have modest benefits in raising HDL cholesterol and lowering TG levels. The most common AEs with statins are muscle AEs and modest liver enzyme elevations. Because niacin and statins have complementary lipid effects and because individually, niacin and statins have been shown in outcomes studies to reduce atherosclerotic coronary artery disease events, the combined use of these 2 agents has significant potential to not only improve the lipid values of patients but improve their lives as well. Equally important is ensuring that the combination of niacin and simvastatin has an acceptable safety profile, with no greater AEs than would otherwise be expected by adding 1 agent to the other.

Prescription omega-3 fatty acids and their lipid effects: physiologic mechanisms of action and clinical implications

Hypertriglyceridemia is a risk factor for atherosclerotic coronary heart disease. Very high triglyceride (TG) levels (≥500 mg/dl [5.65 mmol/l]) increase the risk of pancreatitis. One therapeutic option to lower TG levels is omega-3 fatty acids, which are derived from the oil of fish and other seafood. The American Heart Association has acknowledged that fish oils may decrease dysrhythmias, decrease sudden death, decrease the rate of atherosclerosis and slightly lower blood pressure, and has recommended fish consumption or fish oil supplementation as a therapeutic strategy to reduce cardiovascular disease. A prescription omega-3-acid ethyl esters (P-OM3) preparation has been available in many European nations for at least a decade, and was approved by the US FDA in 2004 to reduce very high TG levels (≥500 mg/dl [5.65 mmol/l]). Mechanistically, most evidence suggests that omega-3 fatty acids reduce the synthesis and secretion of very-low-density lipoprotein (VLDL) particles, and increase TG removal from VLDL and chylomicron particles through the upregulation of enzymes, such as lipoprotein lipase. Omega-3 fatty acids differ mechanistically from other lipid-altering drugs, which helps to explain why therapies such as P-OM3 have complementary mechanisms of action and, thus, complementary lipid benefits when administered with statins. Additional human studies are needed to define more clearly the cellular and molecular basis for the TG-lowering effects of omega-3 fatty acids and their favorable cardiovascular effects, particularly in patients with hypertriglyceridemia.

Risk of Recurrent Venous Thromboembolism Reduced by High Density Lipoproteins.

Venous thrombosis is clinically distinct from arterial thrombosis, with notable differences in thrombus appearance, pathogenic mechanisms, and therapeutic approaches. High-density lipoprotein (HDL) protects against arterial atherothrombosis, but it is not known if HDL protects against recurrent venous thromboembolism. We hypothesized that HDL protects against recurrent venous thrombosis because of its multiple antithrombotic and anti-inflammatory actions. These protective activities include down-regulation of thrombin generation by acting as an anticoagulant cofactor for activated protein C/protein S, enhancement of protective endothelial nitric oxide synthase activity, reduction of leukocyte adhesion to endothelium, and anti-apoptotic effects on endothelium. To test our hypothesis, we prospectively studied 772 patients who had a first episode of spontaneous venous thromboembolism. During an average follow-up observation period of 48 months we recorded the end point of objectively documented, symptomatic recurrent venous thromboembolism. Patients with a genetic deficiency of a plasma coagulation inhibitor deficiency, with a lupus anticoagulant, or with cancer as well as those who required long-term antithrombotic treatment or were on statin therapy were excluded. The relationship between plasma lipoprotein parameters and recurrence of venous thrombosis was evaluated. Plasma apolipoproteins AI and B were measured by immunoassays for all subjects. Using NMR, we determined the levels of ten major lipoprotein subclasses in plasma for 99 patients with venous thrombosis recurrence and for 297 matched patients without recurrence. Recurrent venous thromboembolism developed in 100 of the 772 patients (12.8%). Patients with recurrence compared to those without recurrence had lower mean (±SD) plasma levels of apolipoprotein AI (1.12±0.22 vs. 1.23±0.27 mg/ml, P<0.001) but similar apolipoprotein B levels. The relative risk of recurrence was 0.87 (95% CI, 0.80 to 0.94) for each increase of 0.1 mg/ml in plasma apolipoprotein AI. For patients with apolipoprotein AI above the 67th percentile of the study population values compared with those with lower levels, the relative risk of recurrence was 0.51 (95% CI 0.32–0.83). Comparisons of plasma lipoprotein particle levels from subjects with recurrence versus those without recurrence gave similar results showing that HDL particle concentrations were lower in subjects with recurrence. Patients with high levels of apolipoprotein AI, HDL-cholesterol, and large HDL particles had decreased risk of recurrent venous thromboembolism. In summary, these novel findings that HDL appears to protect against recurrent venous thrombosis may have implications for testing HDL parameters to predict risk and may imply that lipid-altering drugs that increase HDL might reduce the risk for first or recurrent venous thrombotic events.

Extent to Which Accepted Serum Lipid Goals Are Achieved in a Contemporary General Medical Population With Coronary Heart Disease Risk Equivalents

This study examined lipid levels and the use of lipid-altering drugs in a contemporary general medical population without documented coronary heart disease (CHD) but with CHD risk equivalents. On the basis of present national guidelines, the following lipid values (in milligrams per deciliter) were considered optimal for this population: low-density lipoprotein cholesterol <100, high-density lipoprotein (HDL) cholesterol >or=40 in men and >or=50 in women, and non-HDL cholesterol <130 if triglycerides are >or=200. Of 44,052 active patients screened, 877 with CHD risk equivalents as defined by the Adult Treatment Panel III guidelines were identified. Most patients did not meet optimal lipid targets for low-density lipoprotein cholesterol (59%), HDL cholesterol (66%), and non-HDL cholesterol (72%). Indeed, 88% of patients did not meet >or=1 lipid goal. Statins were used in 57% of patients. In patients with low HDL cholesterol, only 4.7% were taking niacin and 4.9% fibrates. In the subgroup of patients with triglycerides >or=200 mg/dl, only 9.5% were taking fibrates and 8.2% niacin. In conclusion, the present analysis highlights the dramatic need to further improve preventive measures in a substantial proportion of high-risk patients with CHD risk equivalents.

Th-P15:165 Study of the effect of vitamin E on the prevention of LDL oxidation by myeloperoxidase

In patients with mixed dyslipidemia characterized by increased triglycerides (TG), decreased high-density lipoprotein (HDL) cholesterol, and increased low-density lipoprotein (LDL) cholesterol, monotherapy with lipid-altering drugs often fails to achieve all lipid targets. This multicenter, double-blind, active-controlled study evaluated ABT-335 (fenofibric acid) in combination with 2 doses of atorvastatin in patients with mixed dyslipidemia. A total of 613 patients with LDL cholesterol ≥130 mg/dl, TG ≥150 mg/dl, and HDL cholesterol <40 mg/dl for men and <50 mg/dl for women were randomly assigned to ABT-335 (135 mg), atorvastatin (20, 40, or 80 mg), or combination therapy (ABT-335 + atorvastatin 20 or 40 mg) and treated for 12 weeks. Combination therapy with ABT-335 + atorvastatin 20 mg resulted in significantly greater improvements in TG (−45.6% vs −16.5%) and HDL cholesterol (14.0% vs 6.3%) compared with atorvastatin 20 mg and LDL cholesterol (−33.7% vs −3.4%) compared with ABT-335. Similarly, significantly greater improvements were observed with ABT-335 + atorvastatin 40 mg in TG (−42.1% vs −23.2%) and HDL cholesterol (12.6% vs 5.3%) compared with atorvastatin 40 mg and LDL cholesterol (−35.4% vs −3.4%) compared with ABT-335 monotherapy. Combination therapy also improved multiple secondary variables. Combination therapy was generally well tolerated with a safety profile consistent with those of ABT-335 and atorvastatin monotherapies. No rhabdomyolysis was reported. In conclusion, ABT-335 + atorvastatin combination therapy resulted in more effective control of multiple lipid parameters than either monotherapy and may be an appropriate therapy for patients with mixed dyslipidemia.

Treatment with high-dose simvastatin reduces secretion of apolipoprotein B-lipoproteins in patients with diabetic dyslipidemia

HMG-CoA reductase inhibitors (statins) are effective lipid-altering drugs for the treatment of dyslipidemia in patients with type 2 diabetes mellitus. We conducted a randomized, double-blind, placebo-controlled, crossover design trial to determine the effects of simvastatin, 80 mg/day, on plasma lipid and lipoprotein levels and on the metabolism of apolipoprotein B (apoB) in VLDL, intermediate density lipoprotein (IDL), and LDL and of triglycerides (TGs) in VLDL. Simvastatin therapy decreased TG, cholesterol, and apoB significantly in VLDL, IDL, and LDL. These effects were associated with reduced production of LDL-apoB, mainly as a result of reduced secretion of apoB-lipoproteins directly into the LDL density range. Statin therapy also reduced hepatic production of VLDL-TG. There were no effects of simvastatin on the fractional catabolic rates of VLDL-apoB or -TG or LDL-apoB. The basis for decreased VLDL-TG secretion during simvastatin treatment is not clear, but recent studies suggest that statins may activate peroxisomal proliferator-activated receptor alpha (PPARalpha). Activation of PPARalpha could lead to increased hepatic oxidation of fatty acids and less synthesis of TG for VLDL assembly.

Non–High-Density Lipoprotein Cholesterol: The Forgotten Therapeutic Target

The National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATP III) has acknowledged mounting evidence of an independent association between hypertriglyceridemia and coronary artery disease risk by issuing guidelines that identify non-high-density lipoprotein (HDL) cholesterol as a secondary target for therapy in patients with elevated triglyceride levels. In 2003, a national survey of outpatient lipid management was conducted for patients undergoing treatment by physicians who were high prescribers of lipid-altering drugs. Results of the NCEP Evaluation Project Utilizing Novel E-Technology II (NEPTUNE II) survey indicated much higher frequencies of low-density lipoprotein (LDL) cholesterol goal achievement compared with frequencies observed in a similarly designed survey in 1997. However, non-HDL cholesterol treatment success in the NEPTUNE II survey was markedly lower than that for LDL cholesterol overall and across risk categories. More aggressive therapy is therefore needed to achieve non-HDL cholesterol goals than LDL cholesterol goals. After achievement of LDL cholesterol goals, non-HDL cholesterol can be managed more aggressively by lowering LDL cholesterol or by using strategies that target a reduction in very-low-density lipoprotein cholesterol. Because the prevalence of hypertriglyceridemia in the United States is high and increasing, enhanced efforts to improve non-HDL cholesterol goal achievement have the potential to produce a substantial effect on public health.

Torcetrapib/atorvastatin combination therapy

Elevated blood levels of low-density lipoprotein cholesterol (LDL-C) are associated with an increased risk for atherosclerotic coronary heart disease (CHD). Atorvastatin is a statin drug that inhibits 3-hydroxy-3-methyl-glutaryl coenzyme A reductase (the rate-limiting step of cholesterol production) and primarily lowers LDL-C levels. Atorvastatin has also been shown to significantly reduce CHD events. However, as with all statins (and all other monotherapy lipid-altering drugs), atorvastatin alone reduces the risk of CHD in only a minority of patients relative to placebo. Conversely, it is low levels of high-density lipoprotein cholesterol that are associated with increased CHD risk. Torcetrapib is a cholesteryl ester transfer protein inhibitor that primarily raises high-density lipoprotein cholesterol levels, and cholesteryl ester transfer protein inhibition has generally been shown to reduce atherosclerosis in rabbits. Taken together, atorvastatin and torcetrapib provide striking improvements in lipid levels, and complementary actions upon important lipid parameters. This review examines the chemistry, mechanism of action, pharmacokinetics, metabolism, safety/tolerability and efficacy of the combination torcetrapib/atorvastatin agent that is currently in development and that provides complementary lipid benefits towards the goal of reducing CHD risk beyond that of atorvastatin alone.

Time as a Variable With Niacin Extended‐Release/Lovastatin vs. Atorvastatin and Simvastatin

Time may be an important variable when evaluating the efficacy of lipid-altering drugs. In this analysis of the Advicor Versus Other Cholesterol-Modulating Agents Trial Evaluation, niacin extended-release/lovastatin 1000/40 mg was as effective as atorvastatin 10 mg and more effective than simvastatin (both 10 mg and 20 mg) in achieving low-density lipoprotein cholesterol and non-high-density lipoprotein cholesterol treatment goals. The titration schedule for this study included the initiation of niacin-extended release/lovastatin 500/20 mg once a day for 4 weeks, titrated to the starting dose of 1000/40 mg after 4 weeks, and then titrated to the final dose of 2000/40 mg. The titration schedule for both atorvastatin and simvastatin was 10 mg per day for 8 weeks and then titrated to 40 mg per day. Using this schedule, 50% of niacin extended-release/lovastatin and atorvastatin patients reached low-density lipoprotein cholesterol and non-high-density lipoprotein cholesterol treatment goals within approximately 7 weeks, compared with simvastatin, in which 50% reached both treatment goals in 13-14 weeks. These time differences may have potential clinical relevance in reducing coronary heart disease risk.

Apolipoprotein L-I is positively associated with hyperglycemia and plasma triglycerides in CAD patients with low HDL

Apolipoprotein L-I (apoL-I) is present on a subset of HDL particles and is positively correlated with plasma triglycerides (TGs). We measured plasma apoL-I levels in coronary artery disease (CAD) subjects with low HDL who were enrolled in an angiographic CAD prevention trial. At baseline, apoL-I levels (n = 136; range, 2.2-64.1 mug/ml) were right skewed with a large degree of variability. Multivariate analysis for biological determinants of apoL-I revealed that the log of VLDL-TG (+0.17; P < 0.05) and hyperglycemia (HG; +0.26; P < 0.005) independently predicted apoL-I level. Hyperglycemic patients (n = 24) had mean apoL-I levels >50% higher than normoglycemic subjects (n = 112; 13.2 vs. 8.3 mug/ml, respectively; P < 0.001). No relationship between apoL-I level and change in CAD was found (r = 0.06, P = 0.49). Simvastatin-niacin therapy did not alter apoL-I levels (n = 34; P = 0.27), whereas antioxidant vitamins alone increased apoL-I by >50% (n = 36; P < 0.01). Genotyping of a known apoL-I polymorphism (Lys166Glu) did not independently account for any of the variability in apoL-I levels. In conclusion, we found TG and HG to be the strongest predictors of apoL-I within a dyslipidemic CAD population. These data provide further characterization of the novel HDL-associated apoL-I.

Lipid-altering agents: the future

Lipid-lowering is established as proven intervention to reduce atherosclerosis and its complications. This article summarises novel developments in the lipid-altering therapies under development. It also discusses other therapeutic targets, such as squalene synthase, microsomal transfer protein, acyl-cholesterol acyl transferase, cholesterol ester transfer protein, peroxosimal proliferator-activating receptors and lipoprotein (a), for which compounds have been developed and have at least reached trials in animal models. Lipid-altering drugs are likely to prove a fast-developing area for novel treatments, as possible synergies exist between new and established compounds for the treatment of atherosclerosis.

Extended-release niacin/lovastatin: the first combination product for dyslipidemia

Many clinical studies have demonstrated that lipid-altering drug treatments, including the use of statin and niacin monotherapy, can be effective in the primary and secondary prevention of coronary heart disease, but only in a minority of patients relative to placebo. Since statins and niacin have entirely different mechanisms of action and predominantly different effects on blood lipid levels, the combined use of both a statin and niacin may confer complementary benefits on multiple lipid parameters, produce a more global improvement in lipid blood levels and result in greater reductions in coronary heart disease risk factors than the administration of either agent alone. This may be of particular importance in patients with complex dyslipidemias, such as those with Type 2 diabetes mellitus and metabolic syndrome. This review summarizes the efficacy and safety of extended-release niacin/lovastatin (Advicor®, Kos Pharmaceuticals Inc.), the first combination product approved for the management of dyslipidemia.

Effects of lipid-altering treatment in diabetes mellitus and the metabolic syndrome

The metabolic syndrome (MS) poses an increased risk for the development of diabetes mellitus and cardiovascular events. The syndrome typically includes dyslipidemia, characterized by elevated plasma triglycerides and low high-density lipoprotein cholesterol concentrations. Retrospective analyses of coronary artery disease outcomes trials in patient subpopulations with diabetes or the MS indicate that lipid-altering therapies provide benefits for patients with the MS at least as much as observed in patients without diabetes or the MS. Analyses of the effects of lipid-altering therapy on the lipid profile in patients with the MS also indicate that beneficial lipid changes are similar in patients with the MS compared with those in patients without the MS. The benefits of statin treatment in patients with the MS have become increasingly clear, and it is likely that further improvements in treatment may be achieved with newer statins or a combination of lipid-altering drugs. Prospective data from clinical trials examining the preventive effects of lipid-altering therapy in MS patients are needed to better define potential benefits and optimal treatment in this population.

Toxicity of antilipidemic agents: facts and fictions.

Dyslipidemias, particularly elevated low-density lipoprotein and low high-density lipoprotein cholesterol, are associated with increased cardiovascular morbidity and mortality and frequently require the use of lipid-lowering drugs to reduce risk. These drugs include statins, fibrates, niacin, and intestinal-acting drugs such as bile acid resins and ezetimibe, which can be used as monotherapy or in combination. Short- and long-term safety concerns often influence the selection of a lipid-altering medication. A balance of efficacy with a favorable safety and tolerability profile is necessary for optimal therapeutic benefits. Recent evidence suggests that there may be differences in the adverse event potential among the available lipid-altering drugs, even within the same class. Awareness of clinically relevant adverse events with monotherapy may assist in the safe selection of individualized lipid-lowering therapy regimens, as well as the potential for drug-drug interactions that may pose a unique challenge in selecting combination drug regimens.

Colesevelam HCl: a non-systemic lipidaltering drug

Colesevelam HCl (WelChol®, Sankyo Pharmaceuticals Inc.) is a bile acid sequestrant polymer, which has been shown to significantly lower low density lipoprotein cholesterol and favourably affect high-density lipoprotein cholesterol blood levels in monotherapy and in combination with statins (HMG-CoA reductase inhibitors). Although it is similar to other bile acid sequestrants in that it binds bile acids and is non-systemic, colesevelam HCl differs in that it has a unique polymer structure that allows for greater tolerability with less potential drug interactions than with resins. Currently, statins are the most commonly prescribed lipid-altering drugs. However, it is not uncommon that patients demonstrate true or perceived intolerances to statin therapy, that are often dose-related and may include elevations in liver or muscle enzyme blood levels, or myalgias or muscle weakness without muscle enzyme elevation. In rare circumstances, myopathy and even rhabdomyolysis can occur with statins. In addition, many statins also have important potential drug interactions. Finally, statin monotherapy is often not sufficient in achieving lipid treatment goals in many severely dyslipidaemic patients and the availability of colesevelam HCl provides a lipid-altering treatment addition to other lipid-altering drugs. From a clinical perspective, such combination therapy is often required to achieve treatment goals [1] in patients with more complicated or severe dyslipidaemia. Colesevelam HCl may also be an alternative in monotherapy for many patients with mild-to-moderate hypercholesterolaemia, as well as in some patients at potential risk from systemic exposure to alternative lipid-altering drugs (such as young children and fertile women).