PubMed Health⌕ Search

Biomedical subjects

J M McKenney

Publications and source records attributed to J M McKenney.

At least 19 recordsLinked to original sources
PubMed2006

Study of the pharmacokinetic interaction between simvastatin and prescription omega-3-acid ethyl esters.

The coadministration of prescription omega-3-acid ethyl esters (P-OM3) with a statin may present a treatment option for patients with mixed hyperlipidemia. This open-label, randomized, 2-way crossover, drug-drug interaction study evaluated the impact of P-OM3 capsules on plasma simvastatin pharmacokinetics in 24 healthy volunteers. Under fasted conditions, 80 mg simvastatin was administered with or without 4 g P-OM3 for two 14-day periods. After 14 days of dosing to achieve steady state, no significant differences were found in either the extent (AUC(tau)) or rate (Cmax) of exposure to simvastatin or its major beta-hydroxy metabolite after coadministration of P-OM3 with simvastatin compared with administration of simvastatin alone. At steady state, the coadministration of P-OM3 capsules did not appear to affect the pharmacokinetics of simvastatin tablets. The combination of P-OM3 capsules and simvastatin appeared to be well tolerated.

Administration, Oral↗
PubMed2001

Effect of niacin and atorvastatin on lipoprotein subclasses in patients with atherogenic dyslipidemia.

This study was conducted to determine the efficacy of atorvastatin and niacin on lipoprotein subfractions in patients with atherogenic dyslipidemia. This was a multicenter, randomized, open-label, parallel-design study of patients with total cholesterol >200 mg/dl, triglycerides between 200 and 800 mg/dl, and apolipoprotein B >110 mg/dl. Patients were randomly assigned to atorvastatin 10 mg or immediate release niacin 3,000 mg daily for 12 weeks following a low-fat diet stabilization period. Lipoprotein subclasses were measured by nuclear magnetic resonance spectroscopy. Atorvastatin and niacin both significantly reduced the concentrations of very low-density lipoprotein (VLDL) particles (-31% and -29%, respectively) and small low-density lipoprotein (LDL) particles (-44% and -35%, respectively). Niacin increased the concentration of large LDL (+75%). Atrovastatin reduced the number of LDL particles more than niacin (31% vs 14%). In patients with atherogenic dyslipidemia, both drugs had important effects on lipoprotein subfractions, which contributed to a reduction in coronary heart disease risk. The drugs equally reduced VLDL subclass levels. Niacin shifted the LDL subclass distribution toward the larger particles, more effectively converted patients from LDL phenotype B to phenotype A, and increased levels of the larger and perhaps more cardioprotective high-density lipoprotein particles. In contrast, atorvastatin preferentially lowered the concentration of small LDL particles without increasing levels of large LDL, and more effectively, reduced LDL particle numbers. Atorvastatin had a preferred LDL effect, whereas niacin had a preferred high-density lipoprotein effect.

Anticholesteremic Agents↗
PubMed2001

Pharmacotherapy of dyslipidemia.

Reducing elevated levels of low-density-lipoprotein cholesterol (LDL-C) significantly reduces the incidence of coronary heart disease (CHD) events and mortality in hypercholesterolemic patients. CHD risk reduction is proportional to LDL-C reduction. Despite this knowledge, many physicians are not applying existing treatment guidelines to the extent required to achieve target LDL-C levels. Target LDL-C levels are not achievable for most patients without drug therapy. Based on their lipid-lowering abilities, safety, and tolerability profiles, the HMG-CoA reductase inhibitors (statins) are the first-line pharmacotherapeutic agents for hypercholesterolemia. The ability of statins to reduce CHD events and total mortality in primary- and secondary-prevention patients also supports this assertion. For combined dyslipidemia, statin monotherapy is a reasonable initial approach in patients with moderate hypertriglyceridemia because statins effectively lower both LDL-C and triglycerides. Fibrates or niacin are effective therapies for severe hypertriglyceridemia. Resins are moderately effective in isolated hypercholesterolemia, and are a useful alternative to statins in pregnant women or patients with liver disease. For severe hyperlipidemia that does not respond to single drug therapy, combination drug therapy may be required. This article reviews the various manifestations of dyslipidemia and assesses the most efficacious treatments.

Cholesterol, LDL↗
PubMed2001

Lipid management: tools for getting to the goal.

The treatment of hypercholesterolemia in the United States begins with the recognition of elevated low-density lipoprotein cholesterol (LDL-C) as the primary target. An optimal LDL-C level has been defined as < 100 mg/dL. The first step in lowering LDL-C continues to be lifestyle modification, which includes a restriction of saturated fat and cholesterol, increased physical activity, and weight loss, if applicable. Approximately half of all patients with elevated LDL-C levels will ultimately need treatment with a lipid-lowering drug to achieve treatment goals. The preferred drug for first-line treatment in most patients is a statin; a bile acid resin or niacin can be used in patients who cannot tolerate statins or who are not candidates for stain therapy. Combination therapy is an option, with several combinations showing efficacy in lowering LDL-C (statin plus bile acid resin, niacin plus bile acid resin) and in lowering both LDL-C and triglycerides (statin plus fibrate, statin plus niacin, bile acid resin plus niacin). Successful lipid management includes treating to reach the LDL-C goal level, treating to reach the non-high-density lipoprotein cholesterol goal level if applicable, and managing other risk factors for coronary heart disease.

Anticholesteremic Agents↗
PubMed2000

Extended-release niacin vs gemfibrozil for the treatment of low levels of high-density lipoprotein cholesterol. Niaspan-Gemfibrozil Study Group.

OBJECTIVE: To provide a direct comparison of agents that raise plasma levels of high-density lipoprotein cholesterol (HDL-C) to help devise strategies for coronary risk reduction. METHODS: In a multicenter, randomized, double-blind trial, we compared the effects of extended-release niacin (Niaspan), at doses increased sequentially from 1000 to 2000 mg at bedtime, with those of gemfibrozil, 600 mg given twice daily, in raising low levels of HDL-C. Enrollment criteria included an HDL-C level of 1.03 mmol/L or less (< or =40 mg/dL), a low-density lipoprotein cholesterol level of 4.14 mmol/L or less (< or =160 mg/dL) or less than 3.36 mmol/L (<130 mg/dL) with atherosclerotic disease, and a triglyceride level of 4.52 mmol/L or less (< or =400 mg/dL). RESULTS: Among 173 patients, 72 (82%) of the 88 assigned to Niaspan treatment and 68 (80%) of the 85 assigned to gemfibrozil treatment completed the study. Niaspan, at 1500 and 2000 mg, vs gemfibrozil raised the HDL-C level more (21% and 26%, respectively, vs 13%), raised the apolipoprotein A-I level more (9% and 11% vs 4%), reduced the total cholesterol-HDL-C ratio more (-17% and -22% vs -12%), reduced the lipoprotein(a) level (-7% and -20% vs no change), and had no adverse effect on the low-density lipoprotein cholesterol level (2% and 0% change vs a 9% increase). Significance levels for comparisons between medications ranged from P<.001 to P<.02. Gemfibrozil reduced the triglyceride level more than Niaspan (P<.001 to P = .06, -40% for gemfibrozil vs -16% to -29% for Niaspan, 1000 to 2000 mg). Effects on plasma fibrinogen levels were significantly favorable for Niaspan compared with gemfibrozil (P<.02), as gemfibrozil increased the fibrinogen level (from 5% to 9%) and Niaspan tended to decrease the fibrinogen level (from -1% to -6%). CONCLUSIONS: In patients with a low baseline HDL-C level, Niaspan at its higher doses provided up to 2-fold greater HDL-C increases, decreases in lipoprotein(a), improvements in lipoprotein cholesterol ratios, and lower fibrinogen levels compared with gemfibrozil. Gemfibrozil gave a greater triglyceride reduction but also increased the low-density lipoprotein cholesterol level, which did not occur with Niaspan.

Adult↗
PubMed2000

Improving cholesterol control in managed care populations.

Cholesterol management has clearly emerged as a top priority for prevention-oriented management of coronary artery disease, and National Cholesterol Education Program (NCEP) guidelines provide the best treatment targets for these efforts. However, even in the highest risk patients, where managed care organizations naturally tend to focus their prevention budgets, the percentage of patients attaining NCEP targets is dismal. To improve success rates in patients requiring pharmacologic therapy, more effective use of new and existing drug therapies may be required. This article provides an update on current options for lipid-modifying drug therapy and offers examples of combination regimens that may assist practitioners in attaining target lipid levels.

Anticholesteremic Agents↗
PubMed1999

A randomized trial of ecadotril versus placebo in patients with mild to moderate heart failure: the U.S. ecadotril pilot safety study.

OBJECTIVE: To determine the short-term safety and tolerability of the addition of ecadotril to conventional therapy in patients with mild to moderate heart failure. METHODS: Fifty ambulatory patients, 18 to 75 years of age, with mild to moderate heart failure, left ventricular ejection fraction </=35%, taking stable doses of angiotensin-converting enzyme inhibitor, diuretics, and optionally digoxin were enrolled in a randomized, double-blind, placebo-controlled dose-escalation study of ecadotril 50 to 400 mg twice daily versus conventional therapy alone. RESULTS: No increases in deaths, serious adverse events, or dropouts from adverse events were observed for the ecadotril group compared with placebo. The serum measures of neurohormonal activation were highly variable. Changes in signs and symptoms of heart failure, New York Heart Association class, and patient self-assessment of symptoms were not observed with ecadotril therapy; however, the study was not designed to detect differences in these parameters. CONCLUSION: In this small pilot study, ecadotril in doses of 50 to 400 mg twice daily was generally well-tolerated and without severe short-term adverse effects in patients with mild to moderate heart failure. Evaluation of the clinical efficacy and long-term safety of ecadotril and other neutral endopeptidase inhibitors in patients with heart failure requires further study.

Adolescent↗
PubMed1999

Pharmacotherapy of dyslipidemia in postmenopausal women: weighing the evidence.

In the United States, coronary heart disease (CHD) is the leading cause of death in women. The incidence of CHD rises dramatically in women following menopause, which can be partially attributed to a more atherogenic lipoprotein profile. For years, observational and epidemiological data have suggested that estrogen and progesterone therapy reduced CHD end points. However, the first prospective trial that evaluated hormone replacement therapy (HRT) for secondary CHD prevention demonstrated no positive cardiovascular benefit of HRT compared with placebo. In interventional studies, the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA)reductase inhibitors significantly reduced CHD outcomes in postmenopausal women, and these agents have emerged as the drugs of choice for primary and secondary CHD prevention. The selective estrogen receptor modulators (SERMs) may have a role in CHD prevention, but long-term clinical trials evaluating end points are needed. An evidence-based approach is necessary when deciding the appropriate pharmacotherapy of dyslipidemia in postmenopausal women.

Aged↗
PubMed1998

A randomized trial of the effects of atorvastatin and niacin in patients with combined hyperlipidemia or isolated hypertriglyceridemia. Collaborative Atorvastatin Study Group.

BACKGROUND: To assess the lipid-lowering effects and safety of atorvastatin and niacin in patients with combined hyperlipidemia or isolated hypertriglyceridemia. METHODS: We performed a randomized, open-label, parallel-design, active-controlled, study in eight centers in the United States. We enrolled 108 patients with total cholesterol (TC) of > or =200 mg/dL, serum triglycerides (TG) > or =200 and < or =800 mg/dL, and apolipoprotein B (apo B) > or =110 mg/dL. Patients were randomly assigned to receive atorvastatin 10 mg once daily (n=55) or immediate-release niacin 1 g three times daily for 12 weeks (n=53). Patients were stratified based on low-density lipoprotein cholesterol (LDL-C): Patients with LDL-C > or =135 mg/dL were considered to have combined hyperlipidemia and patients with LDL-C <135 mg/dL were considered to have isolated hypertriglyceridemia. The primary outcome measure was percent change from baseline in LDL-C. Other lipid levels were evaluated as secondary parameters. RESULTS: Atorvastatin reduced LDL-C 30% and TC 26% from baseline, and increased high-density lipoprotein cholesterol (HDL-C) 4%. Total TG were reduced 17%. Niacin reduced LDL-C 2%, TC 7%, increased HDL-C 25%, and reduced total TG 29% from baseline. There was a significant difference in LDL-C reduction, the primary efficacy parameter, between the two treatment groups (P <0.05, favoring atorvastatin), as well as a significant difference in the improvement in HDL-C (P <0.05, favoring niacin). The effect of atorvastatin was relatively consistent between patients with combined hyperlipidemia and isolated hypertriglyceridemia, whereas there was more variability between these strata in the niacin treatment group. Atorvastatin was better tolerated than niacin. CONCLUSION: Atorvastatin may allow patients with combined hyperlipidemia to be treated with monotherapy and offers an efficacious and well-tolerated alternative to niacin for the treatment of patients with isolated hypertriglyceridemia.

Adult↗
PubMed1998

Patient education and compliance: how to make it cost-effective.

The current level of noncompliance with prescription medications exerts a tremendous burden on the healthcare system in terms of both cost and poor health. The process of developing a program to improve compliance for lipid therapy is twofold. First, patients must be met at their specific level of need. This involves enabling, reinforcing, prompting, and problem solving. Second, the delivery of treatment must be addressed. Large centers and groups should refer lipid patients to a central team of professionals specializing in lipid therapy; or groups of physicians should contract extra patient support out to other groups, such as pharmacies. The implementation of a compliance program will not be immediately cost-effective but will have the long-term benefit of reduced costs through improved health.

Journal Article↗
PubMed1998

The cost of treating dyslipidaemia using National Cholesterol Education Program (NCEP) guidelines.

Coronary heart disease (CHD) is a major cause of death in industrialised countries and places a large burden on society in terms of healthcare resources and lost productivity. US National Cholesterol Education Program (NCEP) guidelines recommend aggressive lipid-modifying therapy for individuals at highest risk for CHD. It has been estimated that more than 50 million individuals in the US (more than one-third of the total population) are candidates for some form of dietary and/or pharmacological intervention to modify their lipid profiles. Most individuals who receive lipid-lowering drug therapy do not meet target goals set by the NCEP; thus, there is a large potential for increased use of drug therapy. Pharmacoeconomic analyses applying NCEP guidelines are sparse; however, available data (using direct costs) suggest that secondary prevention is more cost effective than primary prevention, but that costs associated with primary prevention are generally in line with those of accepted medical interventions. Cost-effectiveness ratios for secondary prevention improved when indirect costs were assessed in one study. A recent randomised prospective 54-week comparative study of statins in 662 patients with hypercholesterolaemia concurrently measured medical outcomes and economic data. Atorvastatin-treated patients were significantly more likely to achieve NCEP goals (overall and at the initial dosage), and to achieve these goals more quickly than patients treated with fluvastatin, lovastatin and simvastatin. The mean cost to reach NCEP goals was consequently lowest for atorvastatin. Results from pharmacoeconomic studies of primary and secondary prevention are therefore in support of NCEP treatment guidelines for hypercholesterolaemia.

Anticholesteremic Agents↗
PubMed1998

The cost of reaching National Cholesterol Education Program (NCEP) goals in hypercholesterolaemic patients. A comparison of atorvastatin, simvastatin, lovastatin and fluvastatin.

OBJECTIVE: Recognising the importance of treating hyperlipidaemia, the National Cholesterol Education Program (NCEP) has established widely accepted treatment goals for low density lipoprotein cholesterol (LDL-C). Medications used most commonly to achieve these LDL-C goals are HMG-CoA reductase inhibitors. The relative resource utilisation and cost associated with the use of reductase inhibitors of different LDL-C lowering efficacy are unknown, but are major health and economic concerns. The objective of this study was to determine the mean total cost of care to reach NCEP goals with various reductase inhibitors. DESIGN: In a randomised, 54-week, 30-centre controlled trial we compared resources used and costs associated with treating patients to achieve NCEP goals using 4 reductase inhibitors: atorvastatin, simvastatin, lovastatin and fluvastatin. PATIENTS AND PARTICIPANTS: The trial studied 662 patients; 318 had known atherosclerotic disease. INTERVENTIONS: Reductase inhibitor therapy was initiated at recommended starting doses and increased according to NCEP guidelines and package insert information. For patients who did not reach the goal at the highest recommended dose of each reductase inhibitor, the resin colestipol was added. MAIN OUTCOME MEASURES AND RESULTS: Patients treated with atorvastatin, compared-with other reductase inhibitors, were more likely to reach NCEP goals during treatment (p < 0.05), required fewer office visits (p < 0.001) and less adjuvant colestipol therapy (p = 0.001). Consequently, the mean total cost of care (1996 values) to reach NCEP goals was lower with atorvastatin [$US1064; 95% confidence interval (CI): $US953 to $US1176] compared with simvastatin ($US1471, 95% CI: $US1304 to $US1648), lovastatin ($US1972; 95% CI: $US1758 to $US2186) and fluvastatin ($US1542; 95% CI: $US1384 to $US1710). Results were similar for patients with or without known atherosclerotic disease. CONCLUSIONS: In patients requiring drug therapy for hypercholesterolaemia, NCEP LDL-C goals are achieved significantly more often using fewer resources with atorvastatin compared with simvastatin, lovastatin or fluvastatin.

Aged↗
PubMed1998

Economic benefits of aggressive lipid lowering: a managed care perspective.

Coronary heart disease (CHD) has high prevalence in the United States and is associated with significant mortality as well as costs to society. Hyperlipidemia is a major and common modifiable risk factor for CHD. In clinical trials, cholesterol-lowering strategies have a dramatic impact on CHD risk, cardiovascular events, and mortality. Cost-effectiveness data have established that clinical and economic benefits are gained by instituting early and aggressive lipid-lowering therapy. We present new evidence for the clinical benefits and cost effectiveness of aggressive lipid-lowering therapy as primary or secondary prevention of CHD and describe strategies that managed care organizations can take to benefit from a lipid management program.

Angioplasty, Balloon, Coronary↗
PubMed1994

A comparison of the efficacy and toxic effects of sustained- vs immediate-release niacin in hypercholesterolemic patients.

OBJECTIVE: To compare escalating doses of immediate-release (IR) and sustained-release (SR) niacin for effectiveness in reducing levels of low-density lipoprotein cholesterol and triglycerides and increasing levels of high-density lipoprotein cholesterol, and for the occurrence of adverse reactions, especially hepatotoxicity. DESIGN: Randomized, double-blind, parallel comparison of IR and SR niacin administered sequentially at 500, 1000, 1500, 2000, and 3000 mg/d, each for 6 weeks. SETTING: Cholesterol research center. PATIENTS: Forty-six adults, 23 in each group, with low-density lipoprotein cholesterol levels greater than 4.14 mmol/L (160 mg/dL) after 1 month of a step 1 National Cholesterol Education Program diet. OUTCOME MEASURES: Fourteen-hour fasting lipid and lipoprotein cholesterol levels, results of clinical laboratory tests, a symptom questionnaire, and withdrawal rates. RESULTS: The SR niacin lowered low-density lipoprotein cholesterol levels significantly more than IR niacin did at the dosage of 1500 mg/d and above, while IR niacin increased high-density lipoprotein cholesterol levels significantly more than SR niacin did at all dosage levels. The reduction in triglyceride levels was similar with IR and SR niacin. Nine (39%) of the 23 patients assigned to the IR dosage form withdrew before completing the 3000-mg daily dose; the most common reasons for withdrawal were vasodilatory symptoms, fatigue, and acanthosis nigricans. Eighteen (78%) of the 23 patients assigned to the SR dosage form withdrew before completing the 3000-mg daily dose; the most common reasons for withdrawal were gastrointestinal tract symptoms, fatigue, and increases in levels of liver aminotransferases, often with symptoms of hepatic dysfunction. None of the patients taking IR niacin developed hepatotoxic effects, while 12 (52%) of the 23 patients taking SR niacin did. CONCLUSION: The SR form of niacin is hepatotoxic and should be restricted from use. The IR niacin is preferred for the management of hypercholesterolemia but can also cause significant adverse effects and should be given only to patients who can be carefully monitored by experienced health professionals.

Adult↗