Nonstatin Lipid-lowering Agents Research Articles

Diagnosis and treatment of dyslipidemia in children and adolescents

Background: Atherosclerotic cardiovascular disease is a major cause of morbidity and mortality worldwide, including in South Korea. Dyslipidemia is an independent risk factor for the development of atherosclerotic cardiovascular diseases. There is strong evidence that atherosclerosis begins early in life and that elevated lipid levels in childhood predict elevated lipid levels into adulthood.Current Concepts: A universal approach for cholesterol screening in all children is recommended. Lipid profiles should be studied for all children aged 9 to 11 years and then for those aged 17 to 21 years, as cholesterol levels may vary after puberty. The non-fasting lipid profile can be as useful in detecting severe genetic dyslipidemias as the fasting lipid profile and thus can be used as a first-line screening in children. The initial treatment for dyslipidemia in a child always begins with a 6-month trial of lifestyle modifications, such as improvements in dietary and physical activity patterns. Statins are as effective in children as in adults and can lower low-density lipoprotein cholesterol levels by up to 50%. Therefore, they are considered first-line therapy for children who meet the criteria for pharmacological therapy.Discussion and Conclusion: Statins and non-statin lipid-lowering agents can lower cholesterol levels with minimal adverse effects in children and adolescents with hypercholesterolemia. However, limited data is currently available on the long-term safety and efficacy of lipid-lowering agents in the pediatric population. Furthermore, non-statin lipid-lowering agents are used far less frequently in children. Therefore, further long-term safety and efficacy studies on lipid-lowering agents in pediatric populations and clinical trials with non-statin lipid-lowering agents are required.

Causal effects of lipid-lowering therapies on aging-related outcomes and risk of cancers: a drug-target Mendelian randomization study.

Despite the widespread use of statins, newer lipid-lowering drugs have been emerging. It remains unclear how the long-term use of novel lipid-lowering drugs affects the occurrence of cancers and age-related diseases. A drug-target Mendelian randomization study was performed. Genetic variants of nine lipid-lowering drug-target genes (HMGCR, PCKS9, NPC1L1, LDLR, APOB, CETP, LPL, APOC3, and ANGPTL3) were extracted as exposures from the summary data of Global Lipids Genetics Consortium Genome-Wide Association Studies (GWAS). GWAS summary data of cancers and noncancerous diseases were used as outcomes. The inverse-variance weighted method was applied as the main statistical approach. Sensitivity tests were conducted to evaluate the robustness, pleiotropy, and heterogeneity of the results. In addition to marked effects on decreased risks of atherosclerotic cardiovascular diseases, genetically proxied lipid-lowering variants of PCKS9, CETP, LPL, LDLR, and APOC3 were associated with longer human lifespans (q<0.05). Lipid-lowering variants of ANGPTL3 and LDLR were associated with reduced risks of colorectal cancer, and ANGPTL3 was also associated with lower risks of gastric cancer (q<0.05). Lipid-lowering LPL variants were associated with decreased risks of hypertension, type 2 diabetes, nonalcoholic fatty liver disease, and bladder cancer (q<0.05). Lipid-lowering variants of PCKS9 and HMGCR were associated with decreased risks of osteoporosis (q<0.05). Lipid-lowering APOB variants were associated with a decreased risk of thyroid cancer (q<0.05). Our study provides genetic evidence that newer nonstatin lipid-lowering agents have causal effects on decreased risks of several common cancers and cardiometabolic diseases. These data provide genetic insights into the potential benefits of newer nonstatin therapies.

Treatment of Patients Chronic Coronary Heart Disease and Type 2 Diabetes Mellitus

The combination of chronic coronary heart disease and type 2 diabetes mellitus in a patient has high medical importance, because relevance of the problem increases every year. Modern requirements for the provision of high-quality medical care to patients with combined pathology require attentive assessment: we can’t deny the pathophysiological relationship of both diseases. Serious changes that occurred in the treatment tactics in relation to such patients require close attention of the medical community. Modern approaches of the therapy of this group of patients include treatment directions that improve the cardiovascular prognosis (lifestyle changes, anti-platelet therapy, antihypertensive therapy, statins and nonstatin lipid-lowering agents, which are indicated for patients who are difficult to tolerate statin treatment, glucose-lowering drugs), as well as careful management of stable angina syndrome (using of antianginal drugs, assessing the possibilities of revascularization). The therapeutic tactics of the new revision offers promising perspective regimens for taking antiplatelet therapy, lipid-lowering drugs. The new line of glucose-lowering drugs has high cardioprotective properties, reduces the intensity of vascular lesions (vasoprotection), and has renoprotective properties. The strategy of choosing glucose-lowering drugs has also undergone some changes: at the moment it is designated as «differentiated», which implies choosing a drug with the highest organoprotective properties. Achievement of target HbA1C levels in the range of 7.0-8.0 % is associated with the lowest patient mortality rate. In addition, to patients with type 2 diabetes mellitus, especially group with coronary heart disease, advised to minimize episodes of hypoglycemic conditions. Aim of this statement is to discuss in detail progressive approaches in the treatment of patients with chronic coronary heart disease and type 2 diabetes mellitus.

Bempedoic Acid for Lipid Management in the Indian Population: An Expert Opinion.

Lipid-lowering is a central theme in the management of patients with atherosclerotic cardiovascular disease (ASCVD)and heterozygous familial hypercholesterolemia (HeFH), with statins being currently used as the first-line lipid-lowering agent (LLAs). Bempedoic acid (BA) has been recently approved for lipid management in ASCVD/HeFH patients. This expert opinion paper brings out the essential conceptto assess the current place of BA in the Indian population. Here we highlight that the majority of the patients with clinical ASCVD may not be receiving the optimal dose of statin, thereby failing to achieve their lipid targets. The addition of BA to statin results in a significant reduction in low-density lipoprotein cholesterol (LDL-C) along with substantial reductions in non-high-density lipoprotein cholesterol (non-HDL-C), apolipoprotein B (ApoB), and high-sensitivity C-reactive protein (hsCRP) levels. For patients who do not achieve LDL-C targets, BA can be an effective add-on alternative to choose among non-statin LLAs. BA is a good choice for statin-intolerant cases, especially in combination with ezetimibe. Given the lack of effect of worsening hyperglycemia or any increase in the occurrence of new-onset diabetes, BA can be used without hesitation in patients with diabetes. The small risk of hyperuricemia could be mitigated with appropriate patient selection and monitoring of serum uric acid levels in patients at high risk of hyperuricemia. We believe BA is an excellent non-statin therapy that is efficacious, well-tolerated, and cost-effective for lipid management in ASCVD, HeFH, and statin-intolerant patients in India.

Lipid-Lowering Therapy in Women of Childbearing Age: a Review and Stepwise Clinical Approach.

Women are less often recognized to have cardiovascular disease (CVD) risk and are underrepresented in randomized trials of lipid-lowering therapy. Here, we summarize non-pharmacologic and pharmacologic strategies for lipid-lowering in women of childbearing age, lipid changes during pregnancy and lactation, discuss sex-specific outcomes in currently available literature, and discuss future areas of research. While lifestyle interventions form the backbone of CVD prevention, some women of reproductive age have an indication for pharmacologic lipid-lowering. Sex-based evidence is limited but suggests that both statin and non-statin lipid-lowering agents are beneficial regardless of sex, especially at high cardiovascular risk. Pharmacologic lipid-lowering therapies, both during the pregnancy period and during lactation, have historically been and continue to be limited by safety concerns. This oftentimes limits lipid-lowering options in women of childbearing age. In this review, we summarize lipid-lowering strategies in women of childbearing age and the impact of therapies during pregnancy and lactation. The limited sex-specific data regarding efficacy, adverse events, and cardiovascular outcomes underscore the need for a greater representation of women in randomized controlled trials. More data on lipid-lowering teratogenicity are needed, and through increased clinician awareness and reporting to incidental exposure registries, more data can be harvested.

Investigating the effect of an education programme on diabetes and lipid lowering medication usage following coronary artery bypass graft surgery.

Guidelines advocate multifactorial cardiovascular risk management in patients with diabetes and atherosclerotic cardiovascular disease. In hospitalised patients with diabetes following coronary artery bypass graft (CABG), we aimed to evaluate the impacts of decision-support algorithms for optimising glycaemia and lipid-lowering. We also assessed the safety of initiating sodium-glucose cotransporter 2 (SGLT2) inhibitors near time of hospital discharge. This was a single-site, pre- and post-intervention analysis of glucose and lipid management in consecutive hospitalised patients with diabetes undergoing CABG surgery. The intervention involved education and decision-support algorithms designed by a multidisciplinary committee to guide cardiac surgery unit clinicians. A total of 200 patients were included in the study. The pre- and post-intervention groups had similar baseline characteristics (HbA1c 7.9 ± 1.9% vs 8.1 ± 1.8%). Of 4092 blood glucose measurements, the incidence of levels between 5 and 10 mmol/L was not different post-intervention (55.5% vs 57.0%; P = 0.441). Fewer endocrinology consultations occurred (59.0% vs 45.0%; P = 0.048) and rates of hypoglycaemia remained low. High-intensity statin was prescribed in >90% pre- and post-intervention, although non-statin lipid-lowering agents remained <10% despite patients not achieving LDL-C targets. No 30-day readmissions for diabetic ketoacidosis occurred in patients prescribed SGLT2 inhibitors. The intervention did not improve inpatient glycaemia or increase non-statin lipid-lowering prescriptions in patients with diabetes following CABG surgery but did reduce reliance on specialty input. Initiation of SGLT2 inhibitor therapy near time of hospital discharge was not associated with safety concerns. Alternative interventions or strategies are required to optimise glycaemia and non-statin lipid-lowering therapy prescribing in this setting.

Lipoprotein(a) and Benefit of PCSK9 Inhibition in Patients With Nominally Controlled LDL Cholesterol

BackgroundGuidelines recommend nonstatin lipid-lowering agents in patients at very high risk for major adverse cardiovascular events (MACE) if low-density lipoprotein cholesterol (LDL-C) remains ≥70 mg/dL on maximum tolerated statin treatment. It is uncertain if this approach benefits patients with LDL-C near 70 mg/dL. Lipoprotein(a) levels may influence residual risk. ObjectivesIn a post hoc analysis of the ODYSSEY Outcomes (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) trial, the authors evaluated the benefit of adding the proprotein subtilisin/kexin type 9 inhibitor alirocumab to optimized statin treatment in patients with LDL-C levels near 70 mg/dL. Effects were evaluated according to concurrent lipoprotein(a) levels. MethodsODYSSEY Outcomes compared alirocumab with placebo in 18,924 patients with recent acute coronary syndromes receiving optimized statin treatment. In 4,351 patients (23.0%), screening or randomization LDL-C was <70 mg/dL (median 69.4 mg/dL; interquartile range: 64.3-74.0 mg/dL); in 14,573 patients (77.0%), both determinations were ≥70 mg/dL (median 94.0 mg/dL; interquartile range: 83.2-111.0 mg/dL). ResultsIn the lower LDL-C subgroup, MACE rates were 4.2 and 3.1 per 100 patient-years among placebo-treated patients with baseline lipoprotein(a) greater than or less than or equal to the median (13.7 mg/dL). Corresponding adjusted treatment hazard ratios were 0.68 (95% confidence interval [CI]: 0.52-0.90) and 1.11 (95% CI: 0.83-1.49), with treatment-lipoprotein(a) interaction on MACE (Pinteraction = 0.017). In the higher LDL-C subgroup, MACE rates were 4.7 and 3.8 per 100 patient-years among placebo-treated patients with lipoprotein(a) >13.7 mg/dL or ≤13.7 mg/dL; corresponding adjusted treatment hazard ratios were 0.82 (95% CI: 0.72-0.92) and 0.89 (95% CI: 0.75-1.06), with Pinteraction = 0.43. ConclusionsIn patients with recent acute coronary syndromes and LDL-C near 70 mg/dL on optimized statin therapy, proprotein subtilisin/kexin type 9 inhibition provides incremental clinical benefit only when lipoprotein(a) concentration is at least mildly elevated. (ODYSSEY Outcomes: Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab; NCT01663402)

The safety and efficacy of Ezetimibe Plus Statins on ASVD and Related Diseases.

It is well known that atherosclerotic vascular disease (ASVD) in the elderly is a global disease with high morbidity, mortality and disability, and plasma LDL-C correction is the most important strategy for ASVD control. However, a large proportion of patients failed to achieve their ideal LDL-C goals after statins use. Ezetimibe, a newly non-statin lipid-lowering agent, is an inhibitor of exogenous cholesterol absorption. Whereby, ezetimibe plus statins may reduce LDL-C more strongly than statins alone. Differed from any other papers published previously, which only involved ezetimibe plus statins for coronary heart disease, the highlight of this paper is to summarize the efficacy and safety of ezetimibe plus statins in all kinds of ASVD subtypes and their related diseases, mainly included aortic atherosclerosis, coronary artery disease, cerebrovascular and peripheral artery diseases. Obviously, this paper is inimitable, which will provide the readers an important reference, especially in treating the elderly with multi-organs atherosclerosis.

Simposio 16: Tratamiento farmacológico (estatinas y combinación de fármacos)

Simposio 16: Diagnóstico y manejo de la dislipidemia diabéticaTratamiento farmacológico (estatinas y combinación de fármacos)Las estatinas constituyen el tratamiento farmacológico indiscutido de la dislipidemia diabética.Las guías recomiendan utilizar estatinas de moderada a alta intensidad como primera línea de tratamiento, dado que reducen el riesgo cardiovascular más allá del nivel de LDL-c. Sin embargo, aún recibiendo dosis máximas de estos fármacos, no todos logran las metas establecidas de LDL-c. Muchos pacientes requerirán agregar agentes hipolipemiantes no estatínicos a modo de tratamiento combinado.

Effect of the polyphenol-rich extract from Allium cepa on hyperlipidemic sprague-dawley rats.

Allium cepa is used for the prevention and treatment of hyperlipidemia-related diseases such as atherosclerosis in the folk. This study was mainly aimed at investigating the effects of A. cepa extract (ACE) enriched in polyphenols on hyperlipidemia Sprague-Dawley (SD) experiment rat models. The levels of total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), malondialdehyde (MDA), and superoxide dismutase (SOD) activity in serum and liver were measured using ELISA kits. In addition, hematoxylin-eosin (HE) technique was used to observe the liver and the aortic arch pathology. Moreover, western blotting (WB) method was applied to analyze LDL receptor (LDLR) and 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase (HMGCR) in liver. As a result, quercetin (2.42mg/g DW) and isoquercitrin (4.60mg/g DW) were the main constituents of ACE using HPLC analysis. Furthermore, ACE reduced the levels of TC, TG, LDL-C, and MDA, and increased HDL levels and elevated SOD activity both in serum and liver in hyperlipidemic SD rats (p<.05). HE results showed that liver fat drops of the rats in ACE group were obviously decreased, and the lipid and foam cells of the aortic arch of the rats in ACE group were markedly ameliorated. WB results showed that ACE promoted the degradation of HMGCR and increased LDLR expression in liver (p<.05). In conclusion, ACE alleviated hyperlipidemia with downregulation of HMGCR and upregulation of LDLR. PRACTICAL APPLICATIONS: Atherosclerosis, a major cardiovascular disease, is the leading cause of mortality and morbidity in the developed countries. Moreover, accumulating data indicate that, during atherosclerosis development, hyperlipidemia is an important risk factor. To date, hyperlipidemia is mainly treated with hyperlipidemic agents including statins, in spite of the side effects and poor tolerance in some patients. In addition, Allium cepa is a medicinal and edible plant. Furthermore, A. cepa is used for the prevention and treatment of hyperlipidemia-related diseases such as atherosclerosis in the folk. But the underlying mechanism is still unclear. In fact, this research showed that A. cepa extract (ACE) alleviated hyperlipidemia with downregulation of HMGCR and upregulation of LDLR, suggesting that ACE might be a potential option for hyperlipidemia as non-statin lipid-lowering agent.

A Review of the 2018 Cholesterol Guidelines: Focus on Nonstatin Lipid-lowering Drugs

The 2018 Cholesterol Clinical Practice Guidelines were released and endorsed by multiple associations including the National Lipid Association, American Diabetes Association, American Pharmacists Association, American Society for Preventive Cardiology, and Preventive Cardiovascular Nurses Association, to name a few. 1 Grundy S.M. Stone N.J. Bailey A.L. et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA /ASPC/NLA/PCNA guideline on the management of blood cholesterol: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2018 Nov 10; ([Epub ahead of print]) Google Scholar Since the prior guideline and addendums, studies have been published showing the benefit of nonstatin lipid-lowering agents. Ezetimibe demonstrated atherosclerotic cardiovascular disease (ASCVD) morbidity reduction (specifically myocardial infarction and stroke) in patients with acute coronary syndrome when added to a moderate-intensity statin, 2 Cannon C.P. Blazing M.A. Giugliano R.P. et al. Ezetimibe added to statin therapy after acute coronary syndromes. N Engl J Med. 2015; 375: 2387-2397 Google Scholar and both evolocumab 3 Sabatine M.S. Giugliano R.P. Keech A.C. et al. Evolocumab and clinical outcomes in patients with cardiovascular disease. N Engl J Med. 2017; 376: 1713-1722 Crossref PubMed Scopus (3169) Google Scholar and alirocumab 4 Odyssey Outcomes Investigators and CommitteeThe Odyssey Outcome Trial Topline results: alirocumab in patients’ after acute coronary syndrome. https://accscientificsession.acc.org/features/2018/03/video-sanofi-regeneronDate: 2018 Date accessed: November 16, 2018 Google Scholar have shown further reduction of ASCVD risk in secondary prevention. Roda Plakogiannis, BS, PharmD, BCPS, CLS, FNLA, is an associate professor of pharmacy practice at the Arnold & Marie Schwartz College of Pharmacy and Health Sciences, Long Island University in Brooklyn, NY. Department Editor Timothy Nguyen, PharmD, BCPS, CCP, FASCP, would like to hear your ideas for future columns at .

Does Treating Vascular Risk Factors Prevent Dementia and Alzheimer's Disease? A Systematic Review and Meta-Analysis.

Epidemiological evidence has associated Alzheimer's disease (AD) with vascular risk factors (VRFs), but whether treatment of VRFs reduces the incidence of dementia and AD is uncertain. To conduct a systematic review and meta-analysis to summarize available data on the impact of treatment of VRFs on dementia and AD incidence. Pertinent studies published until 1 January 2018 were identified from PubMed. Both randomized controlled trials (RCT) and prospective studies that investigated the impact of treatment of VRFs on dementia or AD incidence were included. Eight RCTs and 52 prospective studies were identified. Antihypertensive treatment was associated with a non-significant reduced risk of dementia in RCTs (n = 5; relative risk [RR], 0.84; 95% confidence interval [CI], 0.69-1.02) and prospective studies (n = 3; RR, 0.77; 95% CI, 0.58-1.01) and with reduced AD risk in prospective studies (n = 5; RR = 0.78; 95% CI, 0.66-0.91). In prospective studies, treatment of hyperlipidemia with statins, but not nonstatin lipid-lowering agents, was associated with reduced risk of dementia (n = 17; RR, 0.77; 95% CI, 0.63-0.95) and AD (n = 13; RR, 0.86; 95% CI, 0.80-0.92). The single RCT on statins and dementia incidence showed no association. Data from one RCT and six prospective studies did not support a beneficial impact of antidiabetic drugs or insulin therapy on dementia risk. Current evidence indicates that antihypertensives and statins might reduce the incidence of dementia and AD. Further trials to determine the effect of VRF on AD are needed.

Hypertriglyceridemia: A new paradigm

Low-density lipoprotein cholesterol (LDL-C) has been proven time and again to be independently associated with the risk of cardiovascular diseases (CVD). However, triglycerides (TG) are now also emerging as an important as well as independent risk factor for CVD. International lipid guidelines recommend statins as first-line drugs. However, there always remains a residual risk with statins, especially in the high-risk diabetes subset of patients. The most important reason cited for increased residual CV risk with statins is the non-high density lipoprotein cholesterol component, of which high TGs are an integral part. Several large epidemiological, Mendelian randomisation, population-based and genetic studies are emerging which are pointing towards the fact that high TG leads to CV morbidity and mortality. Pathophysiological basis of hypertriglyceridemia associated with increased CV risk has been attributed to increase circulating chylomicron and TG-rich lipoprotein remnants, increased small dense LDL, heightened risk of endothelial dysfunction and plaque formation. Recent international guidelines recommend TG lowering therapy at TG >200 mg/dl when not controlled by optimal statin therapy. TG levels more than 500 mg/dl, however, require non-statin lipid-lowering agents as primary agents to reduce the risk of acute pancreatitis. Fibrates, niacin and omega 3 fatty acids are recommended as TG-lowering drugs. However, they are not without their share of adverse events. Saroglitazar is a novel dual peroxisome proliferator-activated enzyme agent which has been found to be free of many such adverse events and also adequate in providing dual control over hypertriglyceridemia along with significant glycaemic control.

Pharmacologic Treatment of Dyslipidemia in Diabetes: A Case for Therapies in Addition to Statins

The purpose of the study is to review the use of statins and the role of both non-statin lipid-lowering agents and diabetes-specific medications in the treatment of diabetic dyslipidemia. Statins have a primary role in the treatment of dyslipidemia in people with type 2 diabetes, defined as triglyceride levels >200mg/dl and HDL cholesterol levels <40mg/dL. A number of clinical trials suggest that treatment with a fibrate may reduce cardiovascular events. However, the results of these trials are inconsistent, probably because many of their participants did not have dyslipidemia. The choice of medications used to treat diabetes can have major implications regarding management of dyslipidemia; metformin, GLP-1 agonists, and pioglitazone all have favorable lipid effects. These agents, as well as the new SGLT2 inhibitors, may reduce cardiovascular events. Management of dyslipidemia in people with type 2 diabetes should start with statin therapy and optimal glycemic control with agents that have favorable lipid and cardiovascular effects. We believe that there is a role for adding fenofibrate to moderate-intensity statins in selected patients with true dyslipidemia. We propose an algorithm for selecting add-on medications for diabetes (after metformin) based on lipid status.

Design and Rationale for a Cognitive Outcome Substudy in Ischemic Stroke Patients with High Risk of Cerebral Hemorrhage

Cognitive impairment and dementia are common disabilities after stroke and are associated with increased risks of mortality and recurrent stroke. The prevention of dementia and preserving cognitive function are also important in stroke patients, but its strategy is not established yet. This PICASSO-COG (PreventIon of CArdiovascular events in iSchemic Stroke patients with high risk of cerebral hemOrrhage for reducing COGnitive decline) substudy aims to assess the effects of cilostazol and/or probucol on cognitive function. The substudy aims to assess the reduction in cognitive decline of patients treated with cilostazol and/or probucol in the PICASSO trial. Patients will be assessed using the Korean version of mini-mental state examination and Montreal Cognitive Assessment at 4, 7, 10, 13, 25, 37, and 49 months after randomization. The primary outcome is the change in mini-mental status examination score, compared between treatment groups, with a modified intention-to-treat population using a restricted maximum likelihood-based mixed effects model repeat measurement. This will allow a within-subject correlation due to repeated cognitive tests as well as a different number of measurements among subjects at baseline and each follow-up period. PICASSO-COG is a novel study for assessing the effect on cognitive function of different antiplatelet regimens and the addition of a nonstatin lipid-lowering agent to the current standard statin therapy in patients who have a recent ischemic lesion and prior intracerebral macro- or microbleeds.

Unnecessary lipid-lowering drugs in an outpatient geriatric clinic.

Identify the number of patients in the University of Colorado Seniors Clinic who were prescribed a nonstatin lipid-lowering therapy and describe a pharmacist intervention that can reduce the unnecessary use of these agents.Outpatient geriatrics clinic in a university health system.The University of Colorado Seniors Clinic provides outpatient care for ambulatory patients 75 years of age or older. In 2012, there were 2,000 active patients, with 7,000 clinic visits.All patients prescribed extended-release niacin, ezetimibe, fenofibrate, gemfibrozil, or prescription omega-3-acid ethyl esters were identified. Extended-release niacin, ezetimibe, fenofibrate, and gemfibrozil were deemed necessary if the patient was intolerant to statin therapy or could not attain the cholesterol goal with the maximum tolerated dose of a statin. Fenofibrate, gemfibrozil, and prescription omega-3-acid ethyl esters were considered necessary if the patient had a history of triglycerides above 500 mg/dL. If a pharmacist deemed the medication unnecessary, a note was placed in the medical record and discussed face-to-face with the provider.The number of patients and types of drugs that were prescribed and discontinued; the cost savings to the health system.Fifty-five patients were prescribed a potentially unnecessary lipid-lowering drug. Twenty-three drugs were discontinued, for an estimated $38,660.40 in cost savings.A low percentage of patients were prescribed a nonstatin lipid-lowering agent in this population. However, more than half were deemed unnecessary and were stopped, resulting in significant savings and health benefits. Applying this on a larger scale could result in significant savings and improved health.

Unnecessary lipid-lowering drugs in an outpatient geriatric clinic.

Identify the number of patients in the University of Colorado Seniors Clinic who were prescribed a nonstatin lipid-lowering therapy and describe a pharmacist intervention that can reduce the unnecessary use of these agents. Outpatient geriatrics clinic in a university health system. The University of Colorado Seniors Clinic provides outpatient care for ambulatory patients 75 years of age or older. In 2012, there were 2,000 active patients, with 7,000 clinic visits. All patients prescribed extended-release niacin, ezetimibe, fenofibrate, gemfibrozil, or prescription omega-3-acid ethyl esters were identified. Extended-release niacin, ezetimibe, fenofibrate, and gemfibrozil were deemed necessary if the patient was intolerant to statin therapy or could not attain the cholesterol goal with the maximum tolerated dose of a statin. Fenofibrate, gemfibrozil, and prescription omega-3-acid ethyl esters were considered necessary if the patient had a history of triglycerides above 500 mg/dL. If a pharmacist deemed the medication unnecessary, a note was placed in the medical record and discussed face-to-face with the provider. The number of patients and types of drugs that were prescribed and discontinued; the cost savings to the health system. Fifty-five patients were prescribed a potentially unnecessary lipid-lowering drug. Twenty-three drugs were discontinued, for an estimated $38,660.40 in cost savings. A low percentage of patients were prescribed a nonstatin lipid-lowering agent in this population. However, more than half were deemed unnecessary and were stopped, resulting in significant savings and health benefits. Applying this on a larger scale could result in significant savings and improved health.

Pharmacogenomics, lipid disorders, and treatment options.

Statins form the backbone of lipid-lowering therapy in the prevention of cardiovascular disease. Numerous studies have evaluated the effect of genomics on the clinical efficacy and adverse effects of statins. Several gene variants that can be linked to either the pharmacokinetics or pharmacodynamics of statins have been identified as potentially important, although there are some discrepant findings among studies. Effect sizes are modest for lipid-lowering efficacy and perhaps somewhat larger for risk of myopathy, although results are inconsistent. Pharmacogenomics of nonstatin lipid-lowering agents have not been evaluated to the same extent, given their relatively limited use, although there are some promising candidate genes for further study. Finally, with several new classes of lipid-lowering therapies soon becoming available, there may be a potential application for pharmacogenomics to identify patients ideally suited to receive-or those who should avoid-specific medications.

Cardiometabolic Impact of Non-Statin Lipid Lowering Therapies

Among the range of lipid modifying medications currently available, statins clearly stand as the primary agent capable of reducing cardiovascular risk. While non-statin lipid-lowering drugs improve lipid parameters, their impact on clinical outcomes is less clear, thus necessitating an even closer look at ancillary effects. Recent studies have reported the potential cardiometabolic effects of statins, yet considerably less information has been published about cardiometabolic changes associated with non-statin lipid-lowering agents. This review describes the cardiometabolic profile of non-statin lipid-lowering agents--fibrates, niacin, omega-3 polyunsaturated fatty acids, ezetimibe, and bile acid sequestrants--and therefore aims to facilitate informed decision-making in the pharmacologic management of lipid abnormalities.

A Clinical Review of Statin-Associated Myopathy

Objective: To review the epidemiology, clinical features, proposed mechanisms, risk factors, and management of statin-associated myopathy. Data Sources: Literature searches were conducted in PubMed (1948 to April 2013), TOXLINE, International Pharmaceutical Abstracts (1970 to April 2013), and Google Scholar using the terms statin, hydroxymethylglutaryl-coenzyme A reductase inhibitors, myopathy, myalgia, safety, and rhabdomyolysis. Results were limited to English publications. Study Selection and Data Extraction: All relevant original studies, guidelines, meta-analyses, and reviews of statin-associated myopathy and safety of statins were assessed for inclusion. References from selected articles were reviewed to identify additional citations. Data Synthesis: The 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors remain one of the most effective medications for reducing low-density-lipoprotein cholesterol. Statins are well tolerated by most patients; however, it is estimated that 10% to 15% of patients develop statin-related muscle adverse effects known as statin-associated myopathy. Although clinicians may be aware of statin-associated myopathy, they may not be aware of its clinical presentation. Providers should assess individual patient risk factors before choosing the appropriate statin. A variety of skeletal muscle aches that may not present as a danger to the patient, may affect patient adherence and quality of life. There are several steps that providers can take to properly treat and manage patients with myalgia complaints. Conclusions: Statin-associated myopathy is a clinical problem that contributes to statin therapy discontinuation. Patients who are statin intolerant may be treated with alternative treatment options such as low-dose statins, switching statins, using alternative dosing strategies in statins with longer half-lives, non-statin lipid-lowering agents, and complementary therapies.