Lipid-altering Drugs Research Articles

Altered Basal Lipid Metabolism Underlies the Functional Impairment of Naive CD8+ T Cells in Elderly Humans.

Aging is associated with functional deficits in the naive T cell compartment, which compromise the generation of de novo immune responses against previously unencountered Ags. The mechanisms that underlie this phenomenon have nonetheless remained unclear. We found that naive CD8+ T cells in elderly humans were prone to apoptosis and proliferated suboptimally in response to stimulation via the TCR. These abnormalities were associated with dysregulated lipid metabolism under homeostatic conditions and enhanced levels of basal activation. Importantly, reversal of the bioenergetic anomalies with lipid-altering drugs, such as rosiglitazone, almost completely restored the Ag responsiveness of naive CD8+ T cells. Interventions that favor lipid catabolism may therefore find utility as adjunctive therapies in the elderly to promote vaccine-induced immunity against targetable cancers and emerging pathogens, such as seasonal influenza viruses and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

Pseudohypertriglyceridemia, A Potentially Dangerous Condition Due To Unnecessary Iatrogenic Damage

Background and Aims: Asymptomatic pseudohypertriglyceridemia (due to hyperglycerolemia) in individuals with glycerol kinase deficiency (GKD), is a perplexing and frequently misdiagnosed X-linked recessive enzyme disorder. The apparent hypertriglyceridemia is the result of nearly all clinical laboratories utilizing assays that measure glycerol to report triglyceride values. Many of these patients are often subjected to both aggressive Therapeutic Lifestyle Changes (TLC) and combination lipid-altering drug therapy, which generally prove to be ineffective. We present a patient with an apparent hypertriglyceridemia refractory to (unnecessary) treatment, that suffered severe side effects.

Abstract 206: Randomized Double Blind Clinical Trial on the Effect of Oral Alpha-cyclodextrin on Serum Lipids

Despite numerous therapeutic advances, cardiovascular disease (CVD) remains the leading cause of morbidity and mortality in developed countries. Statins, currently the most effective therapeutic agents for reducing CVD risk, only reduce cardiovascular events by approximately 30%. One possible complementary approach for lowering LDL-C involves the use of oral agents that complex or associate with dietary fats, preventing their intestinal absorption. Bile acid sequestrants are among the oldest lipid-altering drugs and have been known for decades to improve lipid levels and also improve glucose control. Alpha-cyclodextrin (a-CD), a cyclical polymer containing 6 glucose sub-units, is found in many foods, drinks and is sold as an over the counter food supplement. a-CD has a hydrophobic central cavity that binds lipids; one gram of a-CD binds as much as 9 grams of dietary fat and animal studies as well as clinical trials showed that it reduces dietary lipid absorption. This is the first study that evaluated the effect of a-CD in healthy subjects and was designed as a single center, double-blinded, cross-over, placebo controlled clinical pilot study. We screened 103 subjects, males and females, and obtained 75 completed studies (42% male, 58% female, mean age 34 ±12 y.o., BMI 25±4 kg/m2). Eligible subjects were randomized into two arms and received placebo or a-CD (6 grams P.O. a day; two 1 gram tablets per meal) for 12-14 weeks with a one week of wash out period between arms. Several biochemistry and lipid parameters were analyzed and statistics were performed using paired t-test. a-CD was well tolerated and no serious adverse events related to a-CD were observed. Minor GI symptoms were the most common complaint but occurred in less than 7% of subjects on a-CD (vs 3% in placebo). No significant differences were detected on serum lipid and other lipid values but fasting serum glucose (-13% a-CD vs placebo), insulin (-7% a-CD vs placebo), HbA1C (-6% a-CD vs placebo) were decreased. Further positive alterations were present in individuals with higher glucose levels. In conclusion, in healthy subjects, a dose of 6 grams a day of a-CD was able to improve plasma glucose related indexes, in the population studied, but had no significant effect in lipid or lipoprotein plasma levels.

Colesevelam as an Add-On Treatment for Control of Dyslipidemia and Hyperglycemia in Type 2 Diabetes.

Bile acid sequestrants (BASs) have been in use for decades to lower cholesterol. Their low-density lipoprotein (LDL)-lowering effect is the result of binding to and increasing excretion of bile acids, thereby decreasing bile acid return to the liver in the enterohepatic circulation ( 1 Bays H. Dujovne C. Colesevelam HCl: A non-systemic lipid-altering drug. Expert Opin Pharmacother. 2003; 4: 779-790 PubMed Google Scholar ). The liver recovers cholesterol to produce more bile acids by increasing LDL receptor expression, resulting in a drop in plasma LDL cholesterol (LDL-C) levels, typically in the range of 15% to 20% when added to a statin. Earlier generation BASs still in use include cholestyramine and colestipol. In the early 2000s, a second-generation BAS with higher potency in binding bile acids and better tolerability, colesevelam, was introduced, and it became available in Canada in 2012. As suggested in an earlier study of cholestyramine ( 2 Garg A. Grundy S.M. Cholestyramine therapy for dyslipidemia in non-insulin-dependent diabetes mellitus: A short-term, double-blind, crossover trial. Ann Intern Med. 1994; 121: 416-422 Crossref PubMed Scopus (160) Google Scholar ), an additional effect of colesevelam is glucose lowering, with standard doses lowering glycated hemoglobin (A1C) by an average of 0.5% ( 3 Brietzke S.A. Oral antihyperglycemic treatment options for type 2 diabetes mellitus. Med Clin North Am. 2015; 99: 87-106 Abstract Full Text Full Text PDF PubMed Scopus (28) Google Scholar ). The glucose-lowering effect of colesevelam is recognized in the most recent Canadian guidelines for treatment of dyslipidemia in patients with diabetes ( 4 Mancini G.B. Hegele R.A. Leiter L.A. Dyslipidemia. Can J Diabetes. 2013; 37: S110-16 Abstract Full Text Full Text PDF Scopus (10) Google Scholar ) and the 2015 American Diabetes Association Standards of Medical Care in Diabetes ( 5 American Diabetes Association Seven approaches to glycemic treatment. Diabetes Care. 2015; 38: S41-8 Crossref PubMed Scopus (169) Google Scholar ). Here, we review the evidence regarding the clinical efficacy and safety of colesevelam in patients with type 2 diabetes who have dyslipidemia, and we discuss the proposed mechanisms for improved glycemic control when using this agent.

Influence of metabolic syndrome factors and insulin resistance on the efficacy of ezetimibe/simvastatin and atorvastatin in patients with metabolic syndrome and atherosclerotic coronary heart disease risk.

BackgroundMetabolic syndrome (MetS) and insulin resistance (IR) are increasing in prevalence, are associated with higher risk for coronary heart disease (CHD), and may potentially influence the responses to lipid-altering drug therapy. This study evaluated the effects of MetS factors (abdominal obesity, depleted high-density lipoprotein cholesterol [HDL-C], and elevated triglycerides, blood pressure, and fasting glucose) and IR on ezetimibe/simvastatin and atorvastatin treatment efficacy in patients with MetS.MethodsThis post-hoc analysis of a multicenter, 6-week, double-blind, randomized, parallel group study of 1128 subjects with hypercholesterolemia, MetS, and moderately high/high CHD risk evaluated the effects of baseline MetS factors/IR on percent change from baseline in lipids, apolipoproteins, and high-sensitivity C-reactive protein (hs-CRP), after treatment with the usual starting doses of ezetimibe/simvastatin (10/20 mg) versus atorvastatin (10 mg, 20 mg) and next higher doses (10/40 mg versus 40 mg).ResultsEzetimibe/simvastatin and atorvastatin efficacy was generally consistent across MetS factor/IR subgroups. Ezetimibe/simvastatin produced greater incremental percent reductions in LDL-C, non-HDL-C, apolipoprotein B, total cholesterol, and lipoprotein ratios for all subgroups, and larger percent increases in HDL-C and apolipoprotein AI for all but non-obese and HDL-C ≥40 mg/dL subgroups than atorvastatin at the doses compared. Triglycerides, very-LDL-C, and hs-CRP results were more variable but similar between treatment groups.ConclusionThe magnitude of lipid-altering effects produced by each treatment regimen was generally similar across all MetS and IR subgroups. Ezetimibe/simvastatin produced greater percent reductions in most lipid fractions than atorvastatin at the dose comparisons studied, and all treatments were generally well tolerated. (Registered at clinicaltrials.gov: NCT00409773)

National Lipid Association Annual Summary of Clinical Lipidology 2015.

The National Lipid Association (NLA) Annual Summary of Clinical Lipidology 2015 is a summary of principles important to the patient-centered evaluation, management, and care of patients with dyslipidemia. This summary is intended to be a "living document," with future annual updates based on emerging science, clinical considerations, and new NLA Position and Consensus Statements. The goal is to provide clinicians an ongoing resource that translates the latest advances in medical science toward the evaluation and treatment of patients with dyslipidemia. The 2015 NLA Annual Summary of Clinical Lipidology was founded on the principles of evidence-based medicine and is generally consistent with established national and international lipid guidelines. Topics include a general discussion of the 2014 NLA Recommendations for Patient-Centered Management of Dyslipidemia, genetics, secondary causes of dyslipidemia, biomarkers and "advanced lipid testing," medical nutrition, physical activity, obesity, pharmacotherapy, statin safety, lipid-altering drug interactions, lipoprotein apheresis, dyslipidemia in children and adolescence, dyslipidemia in older individuals, race/ethnicity, and women, health information technology and electronic medical records, as well as investigational lipid-altering drugs in development.

Lowering low-density lipoprotein cholesterol levels in patients with type 2 diabetes mellitus.

Type 2 diabetes mellitus (T2DM) is characterized by hyperglycemia, insulin resistance, and/or progressive loss of β-cell function. T2DM patients are at increased risk of micro- and macrovascular disease, and are often considered as representing an atherosclerotic coronary heart disease (CHD) risk equivalent. Interventions directed at glucose and lipid level control in T2DM patients may reduce micro- and macrovascular disease. The optimal T2DM agent is one that lowers glucose levels with limited risk for hypoglycemia, and with no clinical trial evidence of worsening CHD risk. Lipid-altering drugs should preferably reduce low-density lipoprotein cholesterol and apolipoprotein B (apo B) and have evidence that the mechanism of action reduces CHD risk. Statins reduce low-density lipoprotein cholesterol and apo B and have evidence of improving CHD outcomes, and are thus first-line therapy for the treatment of hypercholesterolemia. In patients who do not achieve optimal lipid levels with statin therapy, or who are intolerant to statin therapy, add-on therapy or alternative therapies may be indicated. Additional available agents to treat hypercholesterolemic patients with T2DM include bile acid sequestrants, fibrates, niacin, and ezetimibe. This review discusses the use of these alternative agents to treat hypercholesterolemia in patients with T2DM, either as monotherapy or in combination with statin therapy.

Lipid attainment among patients newly treated with lipid-altering drugs

Objective:Guidelines for preventing and treating patients with coronary artery disease have traditionally focused on reducing low-density lipoprotein cholesterol (LDL-C). Current treatments are effective; however, previous studies have identified a significant proportion of patients that are not achieving the recommended lipid levels. New guidelines were introduced November 2013. The objective of this study was to examine recent practice patterns and factors related to initiating treatment for hypercholesterolemia, which provides a comparative baseline to the introduction of new guidelines.Research design and methods:We conducted a retrospective cohort analysis utilizing laboratory results of lipid profiles and medical claims from January 2007 to September 2011 to identify patients with elevated LDL-C and diagnoses of hypercholesterolemia without prior pharmacotherapy. Pharmacotherapy dispensed, treatment modifications, LDL-C-goal attainment, and potential drug intolerance were evaluated.Results:Overall, among newly treated patients, 70.9% achieved the recommended LDL-C level within the first year of treatment; however, only 19.4% of those with coronary heart disease (CHD) or CHD risk equivalents achieved the more aggressive LDL-C goal of <70 mg/dL (1.8 mmol/L). LDL-C goals were generally achieved with the use of statins; however, a majority of patients underwent treatment modification(s) (e.g., discontinuation or restart). More than half of the patients diagnosed with elevated LDL-C did not initiate pharmacotherapy.Limitations:Data was unavailable for inpatient hospitalizations, family history of cardiovascular diseases, body weight, and height, and likely under-reporting of smoking within claims data.Conclusions:Newly treated patients with elevated LDL-C results generally achieved the recommended and risk-specific LDL-C goal with the use of lipid-altering drugs; however, there still exists a notable population of patients with CHD or CHD risk equivalents who were not treated to goal and a significant number of patients who do not receive lipid-lowering pharmacotherapy. New therapies and prescribing practices are warranted to adequately address these two patient populations.

PCV115 - Treatment Patterns With Lipid-Altering Drugs In High-Risk Vascular Disease In The United Kingdom

PCV115 - Treatment Patterns With Lipid-Altering Drugs In High-Risk Vascular Disease In The United Kingdom

Race-Ethnicity Is a Strong Correlate of Circulating Fat-Soluble Nutrient Concentrations in a Representative Sample of the U.S. Population

Sociodemographic and lifestyle factors exert important influences on nutritional status; however, information on their association with biomarkers of fat-soluble nutrients is limited, particularly in a representative sample of adults. Serum or plasma concentrations of vitamin A, vitamin E, carotenes, xanthophylls, 25-hydroxyvitamin D [25(OH)D], SFAs, MUFAs, PUFAs, and total fatty acids (tFAs) were measured in adults (aged ≥20 y) during all or part of NHANES 2003–2006. Simple and multiple linear regression models were used to assess 5 sociodemographic variables (age, sex, race-ethnicity, education, and income) and 5 lifestyle behaviors (smoking, alcohol consumption, BMI, physical activity, and supplement use) and their relation to biomarker concentrations. Adjustment for total serum cholesterol and lipid-altering drug use was added to the full regression model. Adjustment for latitude and season was added to the full model for 25(OH)D. Based on simple linear regression, race-ethnicity, BMI, and supplement use were significantly related to all fat-soluble biomarkers. Sociodemographic variables as a group explained 5–17% of biomarker variability, whereas together, sociodemographic and lifestyle variables explained 22–23% [25(OH)D, vitamin E, xanthophylls], 17% (vitamin A), 15% (MUFAs), 10–11% (SFAs, carotenes, tFAs), and 6% (PUFAs) of biomarker variability. Although lipid adjustment explained additional variability for all biomarkers except for 25(OH)D, it appeared to be largely independent of sociodemographic and lifestyle variables. After adjusting for sociodemographic, lifestyle, and lipid-related variables, major differences in biomarkers were associated with race-ethnicity (from −44 to 57%), smoking (up to −25%), supplement use (up to 21%), and BMI (up to −15%). Latitude and season attenuated some race-ethnicity differences. Of the sociodemographic and lifestyle variables examined, with or without lipid adjustment, most fat-soluble nutrient biomarkers were significantly associated with race-ethnicity.

Optimal use of lipid-altering therapy: guidelines versus evidence

“an important question is whether adding an additional lipid-altering drug to a statin that specifically modifies HDL cholesterol or triglycerides will further reduce adverse clinical events.”

Beyond Statins: Lipid Management to Reduce Cardiovascular Risk

The discovery that elevated total cholesterol levels and the subsequent understanding that low-density lipoprotein cholesterol levels are associated with higher risk for cardiovascular disease (CVD) has led to the development of lipid management strategies that seek to reduce the burden of CVD. Although substantive progress has been made in reducing death and cardiovascular events, questions remain regarding the optimal approach to further reduce CVD-associated death and disability. Based on current evidence, statins are the clear first-line agents for the management of hyperlipidemia in patients at high risk for cardiovascular events. However, due to the failure of recent clinical trials evaluating antihyperlipidemic drugs, the most appropriate lipid management strategy in patients who cannot tolerate statin therapy or who warrant antihyperlipidemic therapies in addition to statins is a major therapeutic controversy. In this review, we summarize the clinical trial evidence evaluating the efficacy of second-line antihyperlipidemic drug classes for reducing cardiovascular risk, provide recommendations for appropriate use of nonstatin lipid-altering drugs, and identify key areas of future research to support evidence-based lipid management. Given the complexity, magnitude, and burden of CVD, opportunities to improve processes of care and identify new therapeutic options clearly exist.

Common sources and composition of phytosterols and their estimated intake by the population in the city of São Paulo, Brazil

ObjectivePhytosterols have been used alone, or combined with lipid-altering drugs, to reduce cholesterol levels and the burden of cardiovascular disease. Considerable variation in the composition of phytosterols exists and its consumption, in a regular diet, by the Brazilian population is still unknown. Thus, the aim of the present study was to determine the phytosterols content of the most consumed plant foods and to estimate the phytosterols intake by this population. MethodsIntake of plant foods of a representative population of the city of São Paulo (n = 1609), randomly selected on the basis of the Brazilian Institute for Geography and Statistics census data (2010), was obtained by a food frequency questionnaire (FFQ). Foods were chosen on the basis of the Consume Expenditure Survey (2002–2003) and from answers to the FFQ. Phytosterols composition of most consumed greens, legumes, cereals, and seeds, fruits, and vegetable oils was determined by gas chromatography (flame ionization detection). Daily phytosterols intake was estimated in terms of mg per 100 g (mg/100 g−1) of edible portion. Underreporters and overreporters were excluded. ResultsMean (SE) daily phytosterols intake in the diet of the study population was 100.6 (1.2) mg, with β-sitosterol as the largest sterol component (65.4%), followed by campesterol (23.2%), and stigmasterol (10%). No significant changes in daily phytosterols intake were observed after exclusion of underreporters and overreporters. Considerable variation was observed in phytosterols content among the most consumed plant foods. ConclusionsAnalysis of phytosterols composition in most consumed plant foods has shown that phytosterols content varied among food groups. Dietary intake of phytosterols in a large population of the city of São Paulo is in the same range of some countries.

Adiposopathy, Diabetes Mellitus, and Primary Prevention of Atherosclerotic Coronary Artery Disease: Treating “Sick Fat” Through Improving Fat Function with Antidiabetes Therapies

Both obesity and type 2 diabetes mellitus (DM) are worldwide epidemics, an association that is neither incidental nor coincidental. Adipose tissue is as an active endocrine and immune organ whose dysfunction (adiposopathy or "sick fat") is promoted by excessive caloric balance in genetically and environmentally susceptible patients. The resultant adiposopathic responses directly and indirectly contribute to pathologies leading to hyperglycemia, high blood pressure, and dyslipidemia--all major cardiovascular risk factors--as well as to cardiovascular disease (CVD) itself. Toward the goal of primary prevention of CVD among DM patients, clinical trial outcomes evidence support the use of antihypertensive agents, lipid-altering drugs, and antiplatelet agents. Some of the most proactive measures to reduce the onset of cardiovascular risk factors and potentially prevent the onset of DM are early and aggressive nutritional, physical activity, and lifestyle interventions. Such measures improve the functionality of adipose tissue, reduce adiposopathic responses, and thus improve glycemic, blood pressure, and lipid parameters--all of which would be expected to reduce CVD risk. Finally, if nutritional, physical activity, and lifestyle interventions are not successful, and if DM pharmacologic therapies are indicated, then the choice of anti-DM medications should take into consideration the effects of such agents on adipose tissue function and dysfunction, which in turn, affects major CVD risk factors and CVD.

Treatment options for the management of hypertriglyceridemia: Strategies based on the best-available evidence

A severe elevation in triglycerides (TG; ≥500 mg/dL) increases the risk for pancreatitis. TG levels ≥200 mg/dL are associated with a greater risk of atherosclerotic coronary heart disease (CHD). However, no outcomes trials exist to assess the efficacy of TG lowering for preventing pancreatitis in patients with severe hypertriglyceridemia. Similarly, no completed prospective outcomes trial exists to support or refute a reduction in CHD risk resulting from lipid-altering therapy in patients specifically selected for the presence of hypertriglyceridemia. This review examines the available evidence for the use of statins, omega-3 fatty acids, fibrates, and niacin in the management of hypertriglyceridemic patients. Results from CHD outcomes trials support statins as the first-line lipid-altering drug therapy to reduce CHD in hypercholesterolemic patients, and subgroup analyses suggest statins are efficacious in hypertriglyceridemic patients with fasting TG levels <500 mg/dL. Omega-3 fatty acids and fibrates are reasonable first drug options for patients with TG ≥500 mg/dL and often are used to lower TG levels with the objective of reducing pancreatitis risk, although a statin or niacin may also be reasonable options. Combination lipid drug therapy may be needed to achieve both low-density lipoprotein cholesterol and non-high-density lipoprotein cholesterol treatment goals for CHD prevention in patients with elevated TG levels, particularly those with TG ≥500 mg/dL. Additional clinical outcomes data are needed to provide a more evidence-based rationale for clinical lipid management of hypertriglyceridemic patients.

The facts behind niacin

Although low-density lipoprotein cholesterol (LDL-C) lowering represents the mainstay of current lipid treatment, high-density lipoprotein cholesterol (HDL-C) has generated increasing interest as a secondary therapeutic target because of strong evidence that serum HDL-C concentration is inversely associated with coronary heart disease risk. Niacin is a lipid-altering drug that has been used to lower cholesterol since the 1950s. In addition to its LDL-C-lowering effects, niacin is the most effective agent currently available for raising HDL-C. Despite its long history as a lipid-altering drug, only limited data are available regarding its clinical benefit alone and in combination with other agents, and the majority of studies investigating its impact on clinical outcomes are from the pre-statin area. Several studies have demonstrated a beneficial effect of treatment with niacin in combination with statin therapy on surrogate cardiovascular markers (e.g. carotid intima-media thickness). However, the clinical significance of these surrogate markers has been questioned. Two large randomized trials will address whether niacin-statin combination therapy is an appropriate therapeutic alternative to statin monotherapy.

Lapaquistat Acetate

Background— Lapaquistat acetate is a squalene synthase inhibitor investigated for the treatment of hypercholesterolemia. Methods and Results— This report summarizes the phase 2 and 3 results from the lapaquistat clinical program, which was halted at an advanced stage as a result of potential hepatic safety issues. Efficacy and safety data were pooled from 12 studies (n=6151). These were 6- to 96-week randomized, double-blind, parallel, placebo- or active-controlled trials with lapaquistat monotherapy or coadministration with other lipid-altering drugs in dyslipidemic patients, including a large (n=2121) 96-week safety study. All studies included lapaquistat 100 mg daily; 5 included 50 mg; and 1 included 25 mg. The main outcome measures were the percent change in low-density lipoprotein cholesterol, secondary lipid/metabolic parameters, and overall safety. Lapaquistat 100 mg significantly decreased low-density lipoprotein cholesterol by 21.6% in monotherapy and by 18.0% in combination with a statin. It also reduced other cardiovascular risk markers, such as C-reactive protein. Total adverse events were higher for lapaquistat than placebo, although individual events were generally similar. At 100 mg, there was an increase in alanine aminotransferase value ≥3 times the upper limit of normal on ≥2 consecutive visits (2.0% versus 0.3% for placebo in the pooled efficacy studies; 2.7% versus 0.7% for low-dose atorvastatin in the long-term study). Two patients receiving lapaquistat 100 mg met the Hy Law criteria of alanine aminotransferase elevation plus increased total bilirubin. Conclusions— Squalene synthase inhibition with lapaquistat acetate, alone or in combination with statins, effectively lowered low-density lipoprotein cholesterol in a dose-dependent manner. Elevations in alanine aminotransferase, combined with a rare increase in bilirubin, presented potential hepatic safety issues, resulting in termination of development. The lapaquistat experience illustrates the current challenges in lipid-altering drug development. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifiers: NCT00487994, NCT00143663, NCT00143676, NCT00864643, NCT00263081, NCT00286481, NCT00249899, NCT00249912, NCT00813527, NCT00256178, NCT00268697, and NCT00251680.

Safety review of combination drugs for hyperlipidemia

Introduction: Despite statin monotherapy, many high-risk patients are not at recommended low-density lipoprotein cholesterol goals. Moreover, these patients are also likely to exhibit an atherogenic dyslipidemia characterized by decreased high-density lipoprotein cholesterol and elevated triglycerides. As a consequence, combination lipid-altering drug therapies are frequently required to improve the lipid profile. The long-term safety and tolerability of these combination therapies are key determinants for good compliance and cardiovascular benefits.Areas covered: This review summarizes the safety data published on combination drugs for the treatment of hyperlipidemia by examining the various combinations with a statin and also the other combination therapies used when statin treatment is not tolerated. The reader will gain insight into the incidence and severity of the major adverse events expected with combination therapies and the recommendations on the use of these combined treatments. A specific focus is made on muscle-related side effects.Expert opinion: The existing data suggest that ezetimibe, bile acid sequestrants and ω-3 fatty acids appear unlikely to increase the risk of adverse events, particularly myopathy, when used in combination with a statin, even with a high-dose statin. Although the combination of niacin or fenofibrate with moderate-dose statins appears to be safe, prescribing a combination of these drugs with high-dose statins needs caution and requires giving careful information to the patient.

Influence of age, gender, and race on the efficacy of adding ezetimibe to atorvastatin vs. atorvastatin up-titration in patients at moderately high or high risk for coronary heart disease

BackgroundAge, gender, and race are factors that influence atherosclerotic coronary heart disease (CHD) risk and may conceivably affect the efficacy of lipid-altering drugs. MethodsPost hoc analysis of two multicenter, 6-week, double-blind, randomized, parallel-group trials assessed age (<65 and ≥65years), gender, and race (white, black, and other) effects on atorvastatin plus ezetimibe versus up-titration of atorvastatin in hypercholesterolemic patients with CHD risk. High CHD risk subjects with low-density lipoprotein (LDL) cholesterol levels ≥70mg/dL (~1.81mmol/L) during stable atorvastatin 40mg therapy were randomized to atorvastatin 40mg plus ezetimibe 10mg, or up-titrated to atorvastatin 80mg. Moderately high CHD risk subjects with LDL cholesterol levels ≥100mg/dL (~2.59mmol/L) with atorvastatin 20mg were randomized to atorvastatin 20mg plus ezetimibe 10mg, or atorvastatin 40mg. ResultsAlthough some variability existed, age, gender, and race subgroups did not substantially differ from the entire patient population with regard to lipid-altering findings. Ezetimibe plus atorvastatin produced greater percent reductions in LDL cholesterol, total cholesterol, triglycerides, non-high-density lipoprotein (HDL) cholesterol, and apolipoprotein B than up-titration of atorvastatin for all subgroups. HDL cholesterol and apolipoprotein AI changes were small and variable. ConclusionTreatment efficacy in age, gender, and race subgroups did not substantially differ from the entire study population. Ezetimibe combined with atorvastatin generally produced greater incremental reductions in LDL cholesterol and several other key lipid parameters compared with doubling the atorvastatin dose in hypercholesterolemic patients with high or moderately high CHD risk. These results suggest that co-administration of ezetimibe with statins is a useful therapeutic option for treatment of dyslipidemia in differing patient populations.

Ezetimibe added to atorvastatin compared with doubling the atorvastatin dose in patients at high risk for coronary heart disease with diabetes mellitus, metabolic syndrome or neither

Type 2 diabetes mellitus (T2DM) and metabolic syndrome (MetS) are both associated with increased risk for atherosclerotic coronary heart disease (CHD). Thus, it is useful to know the relative efficacy of lipid-altering drugs in these patient populations. A double-blind, parallel group trial of adult patients with hypercholesterolaemia at high-CHD risk receiving atorvastatin 40 mg/day compared atorvastatin 40 mg plus ezetimibe 10 mg (ezetimibe) vs. doubling atorvastatin to 80 mg. This post hoc analysis reports lipid efficacy results in patients grouped by diagnosis of T2DM, MetS without T2DM or neither. Per cent change from baseline at week 6 was assessed for LDL-C, total cholesterol, HDL-C , non-HDL-C , Apo A-I, Apo B and triglycerides. Safety was monitored through clinical and laboratory adverse events (AEs). Compared with doubling atorvastatin, atorvastatin plus ezetimibe resulted in greater reductions in LDL-C, triglycerides, Apo B, non-HDL-C, total cholesterol and lipid ratios in the T2DM, MetS and neither groups. Treatment effects were of similar magnitude across patient groups with both treatments, except triglycerides, which were slightly greater in the T2DM and MetS groups vs. neither group. Changes in HDL-C , Apo A-I and high sensitivity C-reactive protein (hs-CRP) were comparable for both treatments in all three groups. Safety and tolerability profiles were generally similar between treatments and across patient groups, as were the incidence of liver and muscle AEs. Compared with doubling atorvastatin to 80 mg, addition of ezetimibe to atorvastatin 40 mg produced greater improvements in multiple lipid parameters in high-CHD risk patients with T2DM, MetS or neither, consistent with the significantly greater changes observed in the full study cohort (clinical trial # NCT00276484).