A Comparative Overview of Prescription Omega-3 Fatty Acid Products.

An estimated 25% of adults in the United States have elevated triglyceride (TG) levels. This is of particular concern given the evidence for a causal role of TG in the pathway of cardiovascular (CV) disease. Approved prescription omega-3 fatty acid products (RxOM3FAs) contain the long-chain fatty acids docosahexaenoic acid (DHA) and/or eicosapentaenoic acid (EPA) and are effective options for the treatment of high TG levels. RxOM3FAs that contain both EPA and DHA include omega-3-acid ethyl esters (ethyl esters of EPA and DHA; brand and generic products) and omega-3-carboxylic acids (free fatty acids primarily composed of EPA and DHA), while the RxOM3FA icosapent ethyl (the ethyl ester of EPA) contains EPA only. All RxOM3FA products produce substantial TG reduction and other beneficial effects on atherogenic lipid and inflammation-related parameters, blood pressure, and heart rate variability, but products that contain DHA may raise low-density lipoprotein-cholesterol (LDL-C). This commentary provides an overview of hypertriglyceridemia while summarizing the pharmacology, efficacy, and safety of prescription RxOM3FAs.

Dyslipidemia: management using optimal lipid-lowering therapy.

OBJECTIVE: To evaluate current approaches and explore emerging research related to dyslipidemia management. DATA SOURCES: MEDLINE (2004-April 2012) was searched for randomized controlled trials using the terms dyslipidemia and lipid-lowering therapy or statin (>1000 hits). Separate searches (MEDLINE, Google) identified meta-analyses (2010-2011), disease prevalence statistics, and current consensus guidelines (2004-July 2011). Additional references were identified from the publications reviewed. STUDY SELECTION AND DATA EXTRACTION: English-language articles on large multicenter trials were evaluated. DATA SYNTHESIS: National Cholesterol Education Program Adult Treatment Panel III guidelines for the reduction of cardiovascular risk recommend the attainment of specific low-density lipoprotein cholesterol (LDL-C) and non-high-density lipoprotein cholesterol (non-HDL-C) target values, based on an individual's 10-year risk of coronary heart disease or global risk. For most patients unable to achieve recommended lipid level goals with therapeutic lifestyle changes, statins are the first option for treatment. Results of large, well-controlled clinical trials have demonstrated that statins are effective in primary and secondary prevention of cardiovascular disease in diverse populations, including patients with diabetes and the elderly, and that intensive statin therapy provides more effective lipid goal attainment and significantly greater risk reduction in patients with coronary artery disease. Statin therapy is generally well tolerated but may increase the risk of myopathy. Statin use has been associated with increases in hepatic transaminases and an increased risk of diabetes, although the absolute risk of diabetes is low compared with the risk reduction benefit. Combination therapy including a statin may be appropriate for certain populations, but the risk reduction benefits of combination therapy remain unclear. Ezetimibe is an important treatment option for patients with hypercholesterolemia who do not tolerate intensive statin therapy. Although fibrates or niacin improves overall lipid profiles in patients with hypertriglyceridemia or dyslipidemia who are receiving statin therapy, their efficacy in reducing cardiovascular risk remains questionable and their use raises safety and tolerability concerns. CONCLUSIONS: Intensifying lifestyle changes and statin dose should be utilized first in patients not achieving their LDL-C and non-HDL-C goals.

What combination therapy with a statin, if any, would you recommend?

The latest recommended goals for blood lipid levels may require multiple lipid drugs. Lower doses in combination may render more efficacy and safety than highest doses of single agents. Except for isolated hypoalphalipoproteinemia (a low level of high-density lipoprotein cholesterol), therapies will start with a statin. All marketed statins are acceptable. The choice may be based on dose- efficacy and patient's tolerability. High-potency statins (eg, atorvastatin, simvastatin, or rosuvastatin) are often chosen. Currently, generic statins, such as simvastatin, lovastatin, pravastatin, and fluvastatin, offer cost benefits. The choice of added agent depends on the "residual lipoprotein abnormalities" after statin therapy, efficacy, compliance issues, and cost. Approved "combined" preparations improve cost and compliance. To further lower low-density lipoprotein cholesterol, ezetimibe is a safe, efficacious choice, pending resolution of a controversial trial's results. Colesevelam is moderately effective and the best tolerated bile acids sequestrant. In combined dyslipidemias, extended-release niacin is the best tolerated niacin preparation; other quality-controlled immediate-release preparations have similar safety and efficacy but produce more flushing of the skin. Niacin or fenofibrate is effective in normalizing high-density lipoprotein and triglyceride levels persisting after statin therapy. Agents approved by the US Food and Drug Administration and the latest guidelines of the National Cholesterol Education Program, American Heart Association/American College of Cardiology provide choices and indications of drug combinations.

Discordant responses of plasma low-density lipoprotein cholesterol and lipoprotein(a) to alirocumab: A pooled analysis from 10 ODYSSEY Phase 3 studies.

AIMS: Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors consistently reduce low-density lipoprotein cholesterol (LDL-C) by 50-60% and lipoprotein(a) (Lp(a)) by 20-30%, but the mechanism of Lp(a) lowering remains unclear. If Lp(a) is cleared by the LDL receptor, similar to LDL-C, then one would expect PCSK9 inhibition to induce a concordant LDL-C/Lp(a) response in an approximately 2:1 ratio. We aim to determine the prevalence of discordant plasma LDL-C/Lp(a) response to the PCSK9 inhibitor alirocumab. METHODS: This is a post hoc, pooled analysis of 10 randomized controlled trials from the ODYSSEY Phase 3 clinical trial program for alirocumab. Patients enrolled in the trials were high cardiovascular risk and/or with heterozygous familial hypercholesterolemia. The primary end point was prevalence of discordant LDL-C/Lp(a) response to alirocumab at 24 weeks. Discordant response was defined as LDL-C reduction >35% and Lp(a) reduction ≤10%, or LDL-C reduction ≤35% and Lp(a) reduction >10%. RESULTS: Of the 1709 patients in the pooled study cohort, 62.4% were male, and the mean age was 59.2 (SD: 11.0) years. Baseline mean LDL-C was 126.5 (SD: 46.3) mg/dL and baseline median Lp(a) was 46.9 (interquartile range: 21.8-89.0) mg/dL. Total prevalence of discordant LDL-C/Lp(a) response was 21.5% (12.6% with LDL-C >35% reduction and Lp(a) ≤10% reduction; 8.9% with LDL-C ≤35% reduction and Lp(a) >10% reduction). Baseline Lp(a) and familial hypercholesterolemia status did not affect discordance. CONCLUSION: A high prevalence of discordant LDL-C/Lp(a) response was observed with alirocumab, further suggesting that PCSK9 inhibitor therapy with alirocumab reduces plasma Lp(a) through alternative pathways to LDL receptor clearance.

Statin utilization and low-density lipoprotein cholesterol in statin-treated patients with atherosclerotic cardiovascular disease: Trends from a community-based health care delivery system, 2002-2016.

BACKGROUND: A better understanding of patterns in statin utilization and low-density lipoprotein cholesterol (LDL-C) among patients with atherosclerotic cardiovascular disease (ASCVD) in a clinical practice setting is needed. OBJECTIVES: The objective of this study was to examine statin utilization and LDL-C among new statin users with ASCVD. METHODS: This retrospective study used an electronic health record database from a community-based health care system. We identified ASCVD patients ≥21 years of age with a new statin prescription during the study period (2002-2016). Outcomes included high-intensity statin therapy (HIST) prescribing at treatment initiation, medication adherence (defined as proportion of days covered ≥0.80), statin therapy titrations rates, and changes in LDL-C during follow-up. RESULTS: Among 6199 eligible patients, mean follow-up was 16.8 months. At treatment initiation, 16.6% of patients received HIST. Approximately 53% of patients were adherent to statin regimens. Mean percent reduction in LDL-c was 25% during follow-up; 18% of patients, overall, and 30% of those initiating on HIST attained LDL-C reductions >50%. Rates of statin intensity-level increases were 8.4 per 100 person-years. HIST prescribing increased over time, beginning after generic atorvastatin availability and preceded treatment guidelines by two years. Initiation on HIST, higher adherence, and treatment intensification during follow-up were independent predictors of attaining LDL-C goals of <70 mg/dL or <100 mg/dL. CONCLUSIONS: In a community-based health care system, modest LDL-C lowering for secondary ASCVD prevention is likely driven by suboptimal adherence and low HIST prescribing and treatment intensification rates. Clinician and patient education are needed to reduce clinical inertia and improve medication adherence to better manage ASCVD.

ISIS 301012 gene therapy for hypercholesterolemia: sense, antisense, or nonsense?

OBJECTIVE: To present an overview of antisense technology and to review and assess available literature on the chemistry, pharmacology, pharmacokinetics, drug interactions, preclinical and clinical studies, dosing, and adverse events of ISIS 301012 in the treatment of hyperlipidemia. DATA SOURCES: PubMed database searches were conducted from 1966 to May 2007 using the search terms ISIS 301012, antisense, oligonucleotide, hypercholesterolemia, hyperlipidemia, and apolipoprotein B. Bibliographies of relevant review articles and information from the manufacturer were reviewed for additional references. STUDY SELECTION AND DATA EXTRACTION: Available English-language literature, including abstracts, preclinical, and clinical trials, review articles, and scientific presentations were examined. DATA SYNTHESIS: Apolipoprotein B is an important structural protein on the surface of atherogenic lipoproteins such as remnant very-low-density lipoprotein and low-density lipoprotein and facilitates the clearance of these particles from the circulation by binding to the low-density lipoprotein receptor. Overproduction of apolipoprotein B or reduced receptor-mediated clearance of lipoproteins leads to elevated serum cholesterol levels and premature atherosclerosis. ISIS 301012 is an antisense oligonucleotide that inhibits apolipoprotein B production by binding directly to and reducing the expression of apolipoprotein B messenger RNA. In a clinical trial, ISIS 301012 50-400 mg administered weekly via subcutaneous injection for 4 weeks reduced apolipoprotein B by 14.3-47.4% and low-density lipoprotein cholesterol by 5.9-40% at 55 days. The most frequent adverse event was injection-site erythema that resolved spontaneously. Studies are ongoing to further define the safety, efficacy, and pharmacokinetics of ISIS 301012 as add-on therapy in patients with heterozygous and homozygous familial hypercholesterolemia. No pharmacokinetic interactions have been demonstrated with ezetimibe and simvastatin. CONCLUSIONS: ISIS 301012 is the first agent to enter clinical trials utilizing an antisense mechanism for reducing the production of apolipoprotein B. Further studies are needed to verify its safety, efficacy, and position of therapy in the dyslipidemic patient.

PCSK9 Inhibition With Monoclonal Antibodies: Modern Management of Hypercholesterolemia.

Current guidelines for hypercholesterolemia treatment emphasize lifestyle modification and lipid-modifying therapy to reduce the risk for cardiovascular disease. Statins are the primary class of agents used for the treatment of hypercholesterolemia. Although statins are effective for many patients, they fail to achieve optimal reduction in lipids for some patients, including those who have or are at high risk for cardiovascular disease. The PCSK9 gene was identified in the past decade as a potential therapeutic target for the management of patients with hypercholesterolemia. Pharmacologic interventions to decrease PCSK9 levels are in development, with the most promising approach using monoclonal antibodies that bind to PCSK9 in the plasma. Two monoclonal antibodies, alirocumab and evolocumab, have recently been approved for the treatment of hypercholesterolemia, and a third one, bococizumab, is in phase 3 clinical development. All 3 agents achieve significant reductions in levels of low-density lipoprotein cholesterol, as well as reductions in non-high-density lipoprotein cholesterol, apolipoprotein B, and lipoprotein(a). Long-term outcome trials are under way to determine the sustained efficacy, safety, and tolerability of PCSK9 inhibitors and whether this novel class of agents decreases the risk for major cardiovascular events in patients on lipid-modifying therapy. Available data suggest that PCSK9 inhibitors provide a robust reduction in atherogenic cholesterol levels with a good safety profile, especially for patients who fail to obtain an optimal clinical response to statin therapy, those who are statin intolerant or have contraindications to statin therapy, and those with familial hypercholesterolemia.

Statin-associated pleiotropy: possible beneficial effects beyond cholesterol reduction.

Because elevated serum cholesterol levels are strongly associated with coronary heart disease, cholesterol reduction by 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (or statins) has been assumed to be the predominant, if not the only, mechanism underlying the beneficial effects of these drugs in cardiovascular diseases. Subgroup analyses of large clinical trials, however, have suggested that the beneficial effects of statins may extend to mechanisms beyond cholesterol reduction. Indeed, recent experimental and clinical evidence indicates that some of the cholesterol-independent or "pleiotropic" effects of statins may be mediated through improving or restoring endothelial function, enhancing the stability of atherosclerotic plaques, and decreasing oxidative stress and vascular inflammation.

Key articles, guidelines, and consensus papers relative to the treatment of dyslipidemias--2005.

Hypercholesterolemia is a major risk factor for development of coronary heart disease. Proper diagnosis and adequate treatment are vital to reducing morbidity and mortality associated with elevated serum lipid levels. The amount of literature in this area is overwhelming. To aid practitioners and educators in organizing this large body of information, we compiled key articles, guidelines, and consensus papers relative to the treatment of dyslipidemias. Research articles were chosen based on the significance of findings, relevance to practice, quality of research, and timeliness; recent articles were given priority over earlier ones unless they demonstrated groundbreaking findings.

Long-chain omega-3 fatty acids, fibrates and niacin as therapeutic options in the treatment of hypertriglyceridemia: a review of the literature.

Hypertriglyceridemia affects approximately 33% of the US population. Elevated triglyceride levels are independently associated with cardiovascular disease (CVD) risk, and severe hypertriglyceridemia is a risk factor for acute pancreatitis. Guidelines for the management of severe hypertriglyceridemia (≥5.6 mmol/L [≥500 mg/dL]) recommend immediate use of triglyceride-lowering agents; however, statins remain the first line of therapy for the management of mild to moderate hypertriglyceridemia (1.7-5.6 mmol/L [150-499 mg/dL]). Statins primarily target elevated low-density lipoprotein cholesterol levels, but have also been shown to reduce mean triglyceride levels by up to 18% (or 43% in patients with triglyceride levels≥3.1 mmol/L [≥273 mg/dL]). However, individuals with hypertriglyceridemia may need additional reduction in triglyceride-rich lipoproteins and remnant particles to further reduce residual CVD risk. A number of guidelines recommend the addition of fibrates, niacin, or long-chain omega-3 fatty acids if elevated triglyceride or non-high-density lipoprotein cholesterol levels persist despite the use of high-intensity statin therapy. This review evaluates the impact of fibrates, niacin, and long-chain omega-3 fatty acids on lipid profiles and cardiovascular outcomes in patients with hypertriglyceridemia. It also assesses the adverse effects and drug-drug interactions associated with these triglyceride-lowering agents, because although they have all been shown to effectively reduce triglyceride levels in patients with hypertriglyceridemia, they differ with regard to their associated benefit-risk profiles. Long-chain omega-3 fatty acids may be a well-tolerated and effective alternative to fibrates and niacin, yet further large-scale clinical studies are required to evaluate their effects on cardiovascular outcomes and CVD risk reduction in patients with hypertriglyceridemia.

Challenges in the Diagnosis and Treatment of Homozygous Familial Hypercholesterolemia.

Homozygous familial hypercholesterolemia (HoFH) is a rare, genetic disorder characterized by an absence or impairment of low-density lipoprotein receptor (LDLR) function resulting in significantly elevated low-density lipoprotein cholesterol (LDL-C) levels. The cholesterol exposure burden beginning in utero greatly increases the risk for atherosclerotic cardiovascular disease (ASCVD) and premature death. The genetic heterogeneity of HoFH results in a wide range of LDL-C levels among both untreated and treated patients. Diagnosis of HoFH should, therefore, be based on a comprehensive evaluation of clinical criteria and not exclusively LDL-C levels. As treatment goals, the European Atherosclerosis Society and International FH Foundation suggest target LDL-C levels of <100 mg/dL (<2.5 mmol/L) in adults or <70 mg/dL (<1.8 mmol/L) in adults with clinical coronary artery disease or diabetes. The National Lipid Association (NLA) recommends that LDL-C levels be reduced to <100 mg/dL (<2.5 mmol/L) or by at least ≥50 % from pretreatment levels. Conventional therapy combinations that lower atherogenic lipoproteins levels in the blood, such as statins, ezetimibe, bile acid sequestrants and niacin, as well as lipoprotein apheresis, are usually unable to reduce LDL-C levels to recommended targets. Two recently approved agents that reduce lipoprotein synthesis and secretion by the liver are lomitapide, a microsomal triglyceride transfer protein inhibitor, and mipomersen, an apolipoprotein B antisense oligonucleotide. The newly approved inhibitor of proprotein convertase subtilisin/kexin type 9 (PCSK9), evolocumab, also shows promise for the management of FH. Because of the extremely high risk for ASCVD, HoFH patients should be identified early.

The extent of familial hypercholesterolemia instruction in US schools and colleges of medicine, pharmacy, and osteopathic medicine.

BACKGROUND: Familial hypercholesterolemia (FH) is a common autosomal codominant disease characterized by extreme plasma cholesterol concentrations and high risk of early heart disease. FH is underdiagnosed and severely undertreated. This may be due in part to gaps in FH education within medical and pharmacy training programs. OBJECTIVES: To assess the extent to which FH is covered in professional curriculums in accredited schools and colleges of medicine, pharmacy, and osteopathic medicine in the United States. METHODS: An 18-question survey was distributed via e-mail to 288 US schools and colleges of medicine, pharmacy, and osteopathic medicine. RESULTS: Fifty-six of 288 (19.4%) programs responded to the survey. Three were excluded from analysis because of lack of program accreditation and FH instruction. Overall, 43% indicated that FH instruction at their respective institution was perceived to be adequate. More than 90% of the programs indicated that the following topics were covered within the curriculum: FH pathophysiology; associated morbidity and mortality; guideline-recommended low-density lipoprotein cholesterol goals and risk factor management; consequences of poor lipid management; and the screening, diagnosis, and treatment of adult patients. However, instruction was lacking for FH screening methods as one-third of the programs covered cascade screening and only half of the programs reported distinguishing between heterozygous and homozygous FH including differences in treatment approach. CONCLUSIONS: The results suggested important gaps in the coverage of FH in the curriculum, and strategies need to be developed to ensure that FH instruction is sufficient within these professional programs.

National lipid association recommendations for patient-centered management of dyslipidemia: part 1--full report.

The leadership of the National Lipid Association convened an Expert Panel to develop a consensus set of recommendations for patient-centered management of dyslipidemia in clinical medicine. An Executive Summary of those recommendations was previously published. This document provides support for the recommendations outlined in the Executive Summary. The major conclusions include (1) an elevated level of cholesterol carried by circulating apolipoprotein B-containing lipoproteins (non-high-density lipoprotein cholesterol and low-density lipoprotein cholesterol [LDL-C], termed atherogenic cholesterol) is a root cause of atherosclerosis, the key underlying process contributing to most clinical atherosclerotic cardiovascular disease (ASCVD) events; (2) reducing elevated levels of atherogenic cholesterol will lower ASCVD risk in proportion to the extent that atherogenic cholesterol is reduced. This benefit is presumed to result from atherogenic cholesterol lowering through multiple modalities, including lifestyle and drug therapies; (3) the intensity of risk-reduction therapy should generally be adjusted to the patient's absolute risk for an ASCVD event; (4) atherosclerosis is a process that often begins early in life and progresses for decades before resulting a clinical ASCVD event. Therefore, both intermediate-term and long-term or lifetime risk should be considered when assessing the potential benefits and hazards of risk-reduction therapies; (5) for patients in whom lipid-lowering drug therapy is indicated, statin treatment is the primary modality for reducing ASCVD risk; (6) nonlipid ASCVD risk factors should also be managed appropriately, particularly high blood pressure, cigarette smoking, and diabetes mellitus; and (7) the measurement and monitoring of atherogenic cholesterol levels remain an important part of a comprehensive ASCVD prevention strategy.

National Lipid Association Recommendations for Patient-Centered Management of Dyslipidemia: Part 2.

An Expert Panel convened by the National Lipid Association previously developed a consensus set of recommendations for the patient-centered management of dyslipidemia in clinical medicine (part 1). These were guided by the principle that reducing elevated levels of atherogenic cholesterol (non-high-density lipoprotein cholesterol and low-density lipoprotein cholesterol) reduces the risk for atherosclerotic cardiovascular disease. This document represents a continuation of the National Lipid Association recommendations developed by a diverse panel of experts who examined the evidence base and provided recommendations regarding the following topics: (1) lifestyle therapies; (2) groups with special considerations, including children and adolescents, women, older patients, certain ethnic and racial groups, patients infected with human immunodeficiency virus, patients with rheumatoid arthritis, and patients with residual risk despite statin and lifestyle therapies; and (3) strategies to improve patient outcomes by increasing adherence and using team-based collaborative care.

Role of the pharmacist in establishing lipid intervention programs.

Despite the availability of the National Cholesterol Education Program Adult Treatment Panel (ATP) guidelines for the management of hyperlipidemia since 1988, most patients do not achieve their target low-density lipoprotein cholesterol (LDL) goals. With the publication of the most recent guidelines (ATP III), which contain more aggressive treatment recommendations, the cholesterol treatment gap is likely to widen further. Factors responsible for patients not receiving adequate treatment include a lack of focus on asymptomatic diseases, time and reimbursement constraints, inadequate training, a reluctance to prescribe aggressive treatment regimens, and poor communication among health care professionals. Results of several studies evaluating intervention programs indicate that pharmacists can play a key role in improving cholesterol management whether in lipid clinics, community pharmacies, or hospitals. In these intervention programs, pharmacists provided a wide range of functions that included reviewing the medical history, monitoring laboratory values, selecting lipid-lowering therapies, and educating patients regarding drug therapies and the importance of compliance. These interventions produced significant improvements in lipid parameters and in the number of patients who achieved LDL treatment goals. Most important, these interventions were associated with decreases in clinical events. Pharmacist intervention also was highly cost-effective and time efficient. These results suggest that pharmacists are in a unique position and possess the requisite skills to improve the treatment of patients with hyperlipidemia.

Niacin-based therapy for dyslipidemia: past evidence and future advances.

Updated guidelines published recently by the National Cholesterol Education Program place greater emphasis on atherogenic dyslipidemia, characterized by low high-density lipoprotein (HDL) cholesterol; elevated triglycerides; and small, dense, low-density lipoprotein (LDL) particles, as well as the drugs that can alter the condition. Both low HDL cholesterol and elevated triglycerides are independent risk factors for coronary artery disease. Low-density lipoprotein particles can be divided into subclasses with differing atherogenicity. Phenotype A is characterized by large buoyant LDL particles, and phenotype B by small, dense particles associated with increased atherogenicity. The frequency of phenotype B in patients increases as triglyceride levels increase and HDL cholesterol levels decrease. Fibrates and niacin have been shown to improve atherogenic dyslipidemia in clinical trials. Niacin effectively lowers triglycerides, raises HDL cholesterol, and shifts LDL particles to a less atherogenic phenotype (phenotype A). The various niacin formulations available differ in terms of safety and efficacy. When administered alone or in combination with other lipid-modifying agents, niacin prevents progression and promotes regression of coronary atherogenic lesions and reduces coronary risk. Combination therapy is also an effective option for improving multiple lipoprotein abnormalities. In studies, a once-daily, single-tablet combination of niacin extended-release/lovastatin showed additive LDL cholesterol lowering and was more effective than would be anticipated from doubling the component lovastatin dose. Combination products provide a viable strategy for treating the full spectrum of lipid abnormalities seen in some patients, including those with atherogenic dyslipidemia, and will be increasingly used in the treatment of dyslipidemia. Other combination products are currently undergoing clinical testing.

Advances in the understanding and management of dyslipidemia: using niacin-based therapies.

The use of niacin, alone and in combination, for the treatment of dyslipidemia in patients with or at risk for coronary heart disease (CHD), is discussed. Cardiovascular risk is independently predicted not only by high levels of low-density lipoprotein cholesterol (LDL-C), but also low levels of high-density lipoprotein cholesterol (HDL-C) and elevated triglycerides. Moreover, we now understand that LDL particle size and number are associated with differing levels of atherogenicity. Metabolic syndrome, increasingly being recognized as a marker for elevated cardiovascular risk, is associated with atherogenic dyslipidemia characterized by low HDL-C, high triglycerides, and small, dense LDL particles. Controlled clinical studies have shown that niacin therapy effectively increases HDL-C and lowers triglyceride and LDL-C levels while causing a shift toward larger, less atherogenic LDL particles. Niacin, alone or in combination, prevents progression and promotes regression of coronary atherogenic lesions and significantly reduces CHD-related morbidity and mortality. Statin monotherapy causes modest increases in HDL-C and decreases triglycerides, while more potently reducing LDL-C. Combinations of lipid-modifying agents may better address the full spectrum of lipoprotein abnormalities in some patients. Investigations have shown that combining statin therapy with niacin results in additive improvement in the major lipids and lipoproteins and improves clinical outcome. With recently broadened treatment recommendations, it seems likely that combination therapy will be increasingly deemed the appropriate choice for addressing a range of lipid abnormalities.

Muscle symptoms in statin users, associations with cytochrome P450, and membrane transporter inhibitor use: a subanalysis of the USAGE study.

BACKGROUND: Drug interactions have been identified as a risk factor for muscle-related side effects in statin users. OBJECTIVES: The aim was to assess whether use of medications that inhibit cytochrome P450 (CYP450) isozymes, organic anion transporting polypeptide 1B1 (OATP1B1), or P-glycoprotein (P-gp) are associated with muscle-related symptoms among current and former statin users. METHODS: Persons (n = 10,138) from the Understanding Statin Use in America and Gaps in Education (USAGE) internet survey were categorized about whether they ever reported new or worsening muscle pain while taking a statin (n = 2935) or ever stopped a statin because of muscle pain (n = 1516). Univariate and multivariate logistic regression models were used to assess associations between use of concomitant therapies that inhibit CYP450 isozymes, OATP1B1, P-gp, or a combination and muscle-related outcomes. RESULTS: In multivariate analyses, concomitant use of a CYP450 inhibitor was associated with increased odds for new or worse muscle pain (odds ratio [OR] = 1.42; P < .001) or ever having stopped a statin because of muscle pain (OR = 1.28; P = .037). Concomitant use of medication known to inhibit both OATP1B1 and P-gp was also associated with increased odds (OR = 1.80; P = .030) of ever having stopped a statin because of muscle pain. CONCLUSIONS: Concomitant use of medication(s) that inhibit statin metabolism was associated with increased odds of new or worse muscle pain while taking a statin and having previously stopped a statin because of muscle symptoms. These data emphasize the importance of enhancing the capabilities of clinicians and health systems for identifying and reducing statin drug interactions.

JCL Roundtable: health information technology in the management of lipoprotein disorders.

One of the most serious challenges to all physicians is the maintenance of therapy for those chronic disorders that at present cannot be cured. Elevations of low-density lipoprotein and very low-density lipoprotein are among the most common of those disorders. We are now in an era in which 2 fundamental developments of modern technology have come together. These are the supply of effective and safe lipid-lowering drugs as well as the ability to closely monitor pertinent measures in our patients. The rapid conversion of our health care systems into large teams of professionals with direct support from third-party payers has made it possible to coordinate chronic care through electronic medical records and electronic communication. As a result, with effective planning and organization, we can guide our patients toward better adherence to successful medical regimens. These issues are evolving rapidly and have been presented in some detail in the December 2013 issue of the Journal. I was joined in this Roundtable discussion by 3 health professionals who have had extensive experience with the application of health information technology. They are Dr. Karen Aspry and Dr. Alan Brown, both clinical cardiologists, and Dr. Matthew Ito, a Doctor of Pharmacy.