Hyperlipidemias: Pieper JA

Talbert RL, Pieper JA, Ito MK, Anonymous00238. · College of Pharmacy, University of Texas at Austin, USA. · Am J Health Syst Pharm. · Pubmed #12901027 No free full text.

This publication has no abstract.

Dornbrook-Lavender KA, Pieper JA, Roth MT. · Division of Pharmacotherapy, School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. · Ann Pharmacother. · Pubmed #14565805 No free full text.

Abstract: OBJECTIVE: To review relevant literature supporting the use of antihypertensive agents, lipid-lowering agents (i.e., statins), and aspirin therapy for the primary prevention of coronary heart disease (CHD) in an elderly patient population (age >or=65 y). DATA SOURCES: A MEDLINE search (1988-January 2003) was conducted. STUDY SELECTION AND DATA EXTRACTION: Primary and tertiary literature involving the uses of antihypertensives, statins, and aspirin therapy in the elderly were reviewed. DATA SYNTHESIS: Mortality due to CHD in the US population has decreased 40-50% over the last 30 years; however, CHD remains the leading cause of morbidity and mortality in elderly persons. As the population continues to age, the number of older adults eligible for primary prevention will rise. The American Heart Association clinical practice guidelines for the primary prevention of CHD were updated in 2002; however, they are based on findings from clinical trials that enrolled predominantly middle-aged white men. The recommendations for elderly individuals are predominantly extrapolated from subgroup analyses of randomized clinical trials or cohort studies. This literature suggests that elderly persons are candidates for primary prevention measures and experience reductions in coronary events when treated with appropriate therapies. CONCLUSIONS: Data suggest that use of antihypertensives, statins, and aspirin therapy in the elderly appears effective to an extent similar to, and often greater than, that observed in younger patients. We believe these agents should be prescribed to all appropriate high-risk elderly patients. Ongoing and future studies will more clearly elucidate the benefits of primary prevention therapy, particularly in persons >or=75 years of age.

Dornbrook-Lavender KA, Pieper JA. · Department of Pharmacotherapy, University of North Carolina at Chapel Hill School of Pharmacy, Chapel Hill, NC 27599-7360, USA. · Cardiovasc Drugs Ther. · Pubmed #12843689 No free full text.

Abstract: Current strategies for both the primary and secondary prevention of coronary heart disease (CHD) focus on the traditional risk factors, such as hypertension, smoking cessation, and cholesterol, as the primary determinants of the cardiac risk profile, with particular emphasis on the reduction of low-density lipoprotein cholesterol (LDL-C) to targeted goal levels as endorsed by the National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATPIII). Large primary and secondary prevention trials with the hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins) have demonstrated varying reductions in cardiovascular events associated with similar changes in LDL-C levels, suggesting statins may possess additional beneficial effects on other risk factors. Retrospective analyses of many statin trials have evaluated the association between several polymorphic candidate genes (apolipoprotein E, stromelysin-1, beta-fibrinogen, cholesteryl ester transfer protein, lipoprotein lipase, hepatic lipase, and platelet glycoprotein III) which have been identified as predictors of disease severity and both metabolic and clinical response to statin therapy. These results suggest that statin therapy improves plasma lipid profiles in all patients, but preferentially benefits individuals who carry a high risk, variant genotype for these risk factors as compared to individuals with the wild-type genotype. These observations suggest that determining individual patient genotype may be useful in optimizing the benefits of statin therapy. These hypothesis-generating data need to be prospectively evaluated in genotyped patients.

Pieper JA. · Division of Pharmacotherapy, University of North Carolina, Chapel Hill, USA. · Am J Manag Care. · Pubmed #12240702 links to  free full text

Abstract: Niacin is an important therapeutic option for the treatment of dyslipidemias and is the only agent currently available that favorably affects all components of the lipid profile to a significant degree. Niacin has consistently been shown to significantly reduce levels of total cholesterol, low-density lipoprotein (LDL) cholesterol, triglycerides, and lipoprotein (a), while having the greatest high-density lipoprotein (HDL) cholesterol-raising effects of all available agents. Niacin has also been shown to significantly reduce coronary events and total mortality. Niacin is available in 3 formulations: immediate-release (IR), sustained-release (SR), and a newer formulation, niacin extended-release (ER), all of which differ in their pharmacokinetic, efficacy, and safety profiles. Conventional niacin therapy has notable limitations that include flushing, most often seen with IR formulations, and hepatotoxicity, associated with SR formulations. These side effects are related to the absorption rate and subsequent metabolism of niacin as delivered from the different products. Niacin ER has a delivery system allowing absorption rates intermediate to that of niacin IR and SR. As a result, niacin ER achieves the efficacy of niacin IR with a reduced incidence of flushing and without the hepatic effects seen with niacin SR. The pharmacist should be familiar with the differences among and the advantages and disadvantages of each formulation to educate patients and help them achieve the optimal therapeutic benefit of niacin while minimizing adverse effects.

Dornbrook-Lavender KA, Joy MS, Denu-Ciocca CJ, Chin H, Hogan SL, Pieper JA. · Department of Pharmacotherapy, School of Pharmacy, University of North Carolina, Chapel Hill, North Carolina, USA. · Pharmacotherapy. · Pubmed #15843280 No free full text.

Abstract: STUDY OBJECTIVES: To determine the effects of atorvastatin on low-density lipoprotein cholesterol (LDL) particle size and C-reactive protein (CRP) concentrations in patients undergoing long-term hemodialysis. Another objective was to compare the effects of atorvastatin on lipoprotein profiles as determined by direct versus indirect assessment of lipoprotein composition. DESIGN: Randomized, parallel-group substudy. SETTING: Two university-affiliated outpatient hemodialysis centers. PATIENTS: Nineteen patients with LDL levels above 100 mg/dl and with at least two cardiovascular risk factors. INTERVENTION: Patients were randomized in a 1:1 ratio to atorvastatin 10 mg/day or no treatment (control) for 20 weeks. MEASUREMENTS AND MAIN RESULTS: We compared the differences between LDL particle size and CRP levels at baseline and 20 weeks in the atorvastatin versus control groups. Baseline demographic characteristics were similar between the two groups. Atorvastatin therapy was associated with no change in mean LDL particle size (p=0.23) and with a 90% decrease in mean CRP level (p=0.52). When evaluated by standard chemical analysis, atorvastatin therapy reduced total cholesterol levels by 29% (p=0.025) and resulted in nonsignificant reductions in LDL, high-density lipoprotein cholesterol, and triglyceride levels. Treatment with atorvastatin was not associated with significant changes in lipoprotein profile as determined by nuclear magnetic resonance (NMR) spectroscopy. CONCLUSION: Treatment with atorvastatin did not affect LDL particle size but was associated with a sizable, yet nonsignificant, reduction in CRP concentrations. The drug had variable effects on lipoprotein concentrations as determined by chemical and NMR analytical methods. A larger study is necessary to provide definitive information on the effects of atorvastatin on LDL phenotype and CRP in patients with kidney disease.

Pieper JA. · College of Pharmacy, University of New Mexico, 2502 Marble NE, Albuquerque, NM 87131-5691, USA. · Am J Health Syst Pharm. · Pubmed #12901025 No free full text.

Abstract: The pharmacokinetics, efficacy, and safety of niacin and its various formulations are discussed. Niacin has been used for decades for the treatment of dyslipidemia because of its favorable effects on all lipoprotein parameters. Niacin significantly increases high-density lipoprotein cholesterol (HDL-C) more than any other available agent and reduces total cholesterol, low-density lipoprotein cholesterol (LDL-C), lipoprotein (a), and triglycerides. Niacin is currently available in immediate-release (IR), sustained-release (SR), and extended-release (ER) formulations that differ in their dissolution, pharmacokinetic, efficacy, and safety profiles. Important drawbacks to niacin therapy such as cutaneous flushing, associated with IR niacin, and hepatotoxicity, associated with SR niacin, have historically limited its use. The adverse effect profiles of the different niacin formulations can be explained by differences in their dissolution and absorption rates and metabolic disposition, which result in production of metabolites associated with the respective adverse effects. The ER niacin formulation, with an intermediate dissolution rate between the dissolution rates of IR and SR niacin, demonstrates reduced rates of cutaneous flushing compared with IR niacin and hepatotoxic effects compared with SR niacin. Pharmacists need to be familiar with the pharmacokinetics, efficacy, and safety of available niacin formulations so that they can optimally educate both patients and health care providers on the differences among niacin formulations, counsel on the proper selection of a niacin product, and provide strategies for improving tolerance and adherence to therapy.