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Biomedical subjects

James M McKenney

Publications and source records attributed to James M McKenney.

At least 19 recordsLinked to original sources
PubMed2007

Will torcetrapib be the next big thing in coronary heart disease risk reduction?

Scientists are seeking ways to increase high-density lipoprotein (HDL) cholesterol to lower coronary heart disease (CHD). Emerging from this search is torcetrapib, a partial inhibitor of cholesteryl ester transfer protein. Via this mechanism, cholesteryl ester is prevented from being transferred to apolipoprotein B-containing lipoproteins and is retained in HDL particles, where ostensibly it may be delivered directly to the liver for elimination. Proof that this may reduce atherosclerotic vascular disease is provided by population studies of cholesteryl ester transfer protein (CETP) deficiencies and single nucleotide polymorphisms of CETP, and experiments in animal models treated with torcetrapib. Torcetrapib effectively raises HDL cholesterol when used alone and when added to background therapy with atorvastatin. The drug appears to be well tolerated. Large surrogate and survival outcome trials are underway to document its impact on CHD.

Anticholesteremic Agents↗
PubMed2006

Efficacy and safety of torcetrapib, a novel cholesteryl ester transfer protein inhibitor, in individuals with below-average high-density lipoprotein cholesterol levels on a background of atorvastatin.

OBJECTIVES: This study sought to evaluate the efficacy and safety of torcetrapib in patients with low high-density lipoprotein cholesterol (HDL-C) levels receiving background atorvastatin. BACKGROUND: Elevating HDL-C levels may reduce the residual cardiovascular risk that is observed in patients treated with statin therapy. Torcetrapib (a cholesteryl ester transfer protein inhibitor) increases HDL-C and decreases low-density lipoprotein cholesterol (LDL-C). METHODS: This was a multicenter, double-blind, randomized trial. Patients with below-average HDL-C (men <44 mg/dl; women <54 mg/dl) who were eligible for statin therapy according to National Cholesterol Education Program Adult Treatment Panel III guidelines or who had LDL-C >130 mg/dl at screening entered an 8-week run-in period with atorvastatin 20 mg/day before randomization (n = 174) to torcetrapib 10, 30, 60, or 90 mg/day or placebo for 8 weeks. Atorvastatin was continued during treatment with torcetrapib. RESULTS: After 8 weeks, the percent change from baseline with torcetrapib (least-squares mean difference from placebo) ranged from 8.3% to 40.2% for HDL-C (p < or = 0.0001 for 30-mg and higher doses) and from 0.6% to -18.9% for LDL-C (p < 0.01 for 60-mg and 90-mg doses). Particle size for both HDL and LDL increased with torcetrapib. The incidence of all-causality and treatment-related adverse events was similar across placebo and torcetrapib treatment groups with no evidence of a dose-related response. In some treatment groups, small increases in systolic and diastolic blood pressures were noted. CONCLUSIONS: In statin-eligible patients, torcetrapib plus background atorvastatin resulted in substantial, dose-dependent increases in HDL-C, accompanied by additional decreases in LDL-C beyond those seen with atorvastatin alone. Torcetrapib plus atorvastatin was generally well tolerated.

Adult↗
PubMed2006

Efficacy and safety of torcetrapib, a novel cholesteryl ester transfer protein inhibitor, in individuals with below-average high-density lipoprotein cholesterol levels.

OBJECTIVES: This study was designed to evaluate the efficacy and safety of torcetrapib, a cholesteryl ester transfer protein (CETP) inhibitor, in subjects with low high-density lipoprotein cholesterol (HDL-C) levels. BACKGROUND: Evidence suggests HDL-C is atheroprotective. A proven mechanism for increasing the level of HDL-C is the inhibition of CETP. METHODS: A total of 162 subjects with below-average HDL-C (men <44 mg/dl; women <54 mg/dl) who were not taking lipid-modifying therapy were randomized to double-blind treatment with torcetrapib 10, 30, 60, or 90 mg/day or placebo ( approximately 30 subjects per group). RESULTS: The percent change from baseline to Week 8 with torcetrapib (least-squares mean difference from placebo) was dose-dependent and ranged from 9.0% to 54.5% for HDL-C (p < or = 0.0001 for 30 mg and higher doses) and from 3.0% to -16.5% for low-density lipoprotein cholesterol (LDL-C) (p < 0.01 for 90-mg dose). Low-density lipoprotein cholesterol lowering was less in subjects with higher (>150 mg/dl) versus lower levels of baseline triglycerides; at 60 mg, the change in LDL-C was 0.1% versus -22.2% (p < 0.0001), respectively. Particle size for both HDL and LDL increased with torcetrapib. There were no dose-related increases in the frequency of adverse events. Significant blood pressure increases were noted in 2 of 140 subjects. CONCLUSIONS: Torcetrapib resulted in substantial dose-dependent elevations in HDL-C, accompanied by moderate decreases in LDL-C at the higher doses. Torcetrapib was generally well tolerated.

Adult↗
PubMed2006

Safety and efficacy of long-term co-administration of fenofibrate and ezetimibe in patients with mixed hyperlipidemia.

OBJECTIVES: This study sought to determine the long-term safety and efficacy of co-administered fenofibrate (FENO) and ezetimibe (EZE) in patients with mixed hyperlipidemia. BACKGROUND: Both EZE and FENO offer complementary benefits to the lipid profile of patients with mixed hyperlipidemia. METHODS: After completing the 12-week randomized, double-blind base study that compared EZE 10 mg, FENO 160 mg, FENO 160 mg plus EZE 10 mg, and placebo in patients with mixed hyperlipidemia, patients continued into a double-blind, 48-week extension phase. Those patients in the FENO plus EZE and FENO groups continued on their respective base study treatment, and patients in the EZE and placebo groups were switched to FENO plus EZE and FENO, respectively. RESULTS: Of the 587 patients who completed the base study, 576 continued into the extension study (n = 340 in FENO plus EZE and n = 236 in FENO). The FENO plus EZE produced significantly greater reductions in low-density lipoprotein-cholesterol compared with FENO (-22% vs. -9%, respectively; p < 0.001). There were also significantly greater improvements in triglycerides, high-density lipoprotein cholesterol (HDL-C), total cholesterol, non-HDL-C, and apolipoprotein B with FENO plus EZE compared with FENO. Changes in apolipoprotein A-I and high-sensitivity C-reactive protein were similar between groups. Overall, FENO plus EZE was well tolerated during the extension study. The proportion of patients with consecutive elevations of alanine aminotransferase/aspartate aminotransferase > or =3 times upper limit of normal were similar between the FENO plus EZE (1.2%) and FENO (1.7%) groups. No cases of creatine phosphokinase elevations > or =10 times upper limit of normal or myopathy were observed in either group. CONCLUSIONS: Long-term, 48-week co-administration of FENO plus EZE was well tolerated and more efficacious than FENO in patients with mixed hyperlipidemia.

Adult↗
PubMed2006

Final conclusions and recommendations of the National Lipid Association Statin Safety Assessment Task Force.

This article summarizes the final conclusions of the National Lipid Association (NLA) Statin Safety Task Force, based on a review and independent research of New Drug Application (NDA) information, US Food and Drug Administration (FDA) Adverse Event Reporting System (AERS) data, cohort and clinical trial results, and analysis of administrative claims database information and the assessment of its 4 Expert Panels, which focused on issues of statin safety with regard to liver, muscle, renal, and neurologic systems. Practical guidance in the form of recommendations to health professionals who manage the coronary artery disease risk of patients with statin therapy is provided.

Adverse Drug Reaction Reporting Systems↗
PubMed2006

Statin safety: an assessment using an administrative claims database.

The large administrative databases of health plans contain information on drug-related medical adverse events (AE) and constitute an increasingly powerful tool for the assessment of drug safety. We conducted a retrospective observational study using an administrative managed care claims database covering 9 million members from diverse regions of the United States. Patients aged >or=18 years who received >or=2 prescriptions for lipid-lowering drugs between July 1, 2000 and December 1, 2004 were included in the study. Hospitalizations with diagnosis codes (International Classification of Diseases, 9th Revision, Clinical Modification [ICD-9]) related to muscle, kidney, and liver were determined for patients exposed to 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins), fibrates, extended-release niacin, cholesterol absorption inhibitors, or statin combination therapy. A total of 473,343 patients contributed 490,988 person-years of monotherapy and 11,624 person-years of combination dyslipidemia therapy. Rates of hospitalization due to AEs in patients on monotherapy with currently available statins were similar, whereas the incidence of hospitalization for muscle disorders increased 6.7-fold with cerivastatin therapy. Patients who received a lipid-lowering medication with a concomitant cytochrome P450 3A4 (CYP3A4) inhibitor had a 6-fold increased rate of muscle disorders, including rhabdomyolysis. Hypertension was associated with a 5-fold increase in both muscle and renal events, whereas patients with diabetes mellitus had a 2.5-fold increased risk of renal events. No hospitalized cases of the index AEs were observed in study subjects during the 6-month period before initiation of the lipid-lowering drug. Statin monotherapy as currently prescribed is generally well tolerated and safe.

Chemical and Drug Induced Liver Injury↗
PubMed2006

An assessment of statin safety.

Recently, statin safety and potential drug interactions have received close attention in the consumer and medical press. In particular, rosuvastatin, the most recent statin introduced into the US market, has been the object of much speculation. Many of these reports have lost sight of the proven efficacy of statins in coronary disease prevention at a time when coronary heart disease is the number one killer of adults, and have failed to frame the potential drug toxicity in the context of this benefit. Summarized here are the conclusions of the National Lipid Association's Statin Safety Assessment Task Force, which reviewed extensive new drug application (NDA) and postmarketing data for all the currently marketed statins regarding their effect on the liver, muscle, renal, and neurologic systems. The task force found that, overall, hepatic, renal, or neurologic function does not appear to be compromised by statin use. They do not recommend routine monitoring of these systems but do recommend ongoing surveillance of symptomatic patients. With respect to muscle toxicity, the task force's Muscle Expert Panel concluded that the incidence of myopathy and rhabdomyolysis is low and appears to be dose-related, rather than associated with the degree of low-density lipoprotein cholesterol lowering and also appears to be related to the individual statin used. For example, from the rosuvastatin NDA database and additional postmarketing data, the overall incidence of myopathy was found to be lower than that observed with other statins. Administrative claims data of hospitalization rates for adverse events in statin patients confirm the task force conclusion that, overall, statins are safe and well tolerated when used as monotherapy.

Advisory Committees↗
PubMed2006

Effectiveness and cost-effectiveness of rosuvastatin, atorvastatin, and simvastatin among high-risk patients in usual clinical practice.

BACKGROUND: Assessments of the effectiveness and cost-effectiveness of treatment with statins in high risk patients in routine clinical practice are needed. The objective of the present study was to estimate the clinical effectiveness and cost-effectiveness of rosuvastatin compared with atorvastatin or simvastatin among high-risk patients as treated in routine clinical practice. METHODS: Patients aged 18 to 79 years with coronary heart disease (CHD) or equivalent who initiated treatment with atorvastatin, rosuvastatin, or simvastatin were included. Primary outcome variables were the percent reduction in low-density lipoprotein cholesterol (LDL-C), achievement of the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) LDL-C goal, treatment costs, and cost-effectiveness. Regression models were used to adjust outcome measures for age, sex, CHD, baseline LDL-C, and therapy duration. A decision analytic model was used to assess incremental cost-effectiveness. RESULTS: Of the 775 eligible patients, rosuvastatin patients had higher baseline LDL-C levels (156 mg/dL vs 142 mg/dL or 137 mg/dL, respectively) compared with atorvastatin or simvastatin. Adjusted for baseline factors, percent LDL-C reduction was significantly greater with rosuvastatin versus atorvastatin or simvastatin (37% vs 28% or 27%, respectively; P <.05). The estimated percentage of patients attaining NCEP ATP III goal was higher (P <.05) for rosuvastatin (69.7%) compared with atorvastatin (54.8%) or simvastatin (51.2%), adjusted for baseline characteristics. Rosuvastatin patients also had the lowest annualized treatment costs (934dollars vs 1050 dollars or 1545 dollars for atorvastatin or simvastatin). Rosuvastatin was more effective and less costly than atorvastatin and at current branded and generic prices of simvastatin. A 60% to 68% discount from simvastatin branded price was needed to achieve equivalent cost-effectiveness as rosuvastatin. CONCLUSIONS: In clinical practice, rosuvastatin is more effective and cost-effective in lowering LDL-C and in attainment of ATP III LDL-C goals compared with atorvastatin or simvastatin among high-risk patients.

Adolescent↗
PubMed2005

Pharmacologic options for aggressive low-density lipoprotein cholesterol lowering: benefits versus risks.

Lessons from recent end point trials of lipid-lowering drugs indicate that patients at very high risk for coronary artery disease (CAD) benefit from treatment that lowers low-density lipoprotein (LDL) cholesterol plasma levels to < or = 1.81 mmol/L (< or = 70 mg/dL), that patients with > or = 2 risk factors benefit from treatment that lowers plasma LDL cholesterol to <2.59 mmol/L (<100 mg/dL), and that a significant reduction in CAD event rates is most often associated with a minimum plasma LDL cholesterol reduction of 30%. Recently, the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) recommendations were amended to incorporate these lessons. To reach these more aggressive goals and plasma LDL cholesterol reductions, more aggressive therapies will be required. The best way to implement more aggressive therapy is to start with one of the more potent statins, especially atorvastatin or rosuvastatin, or higher doses of other statins. This approach alone is likely to achieve treatment goals in 50% to 80% of patients. For patients needing additional plasma LDL cholesterol lowering, combination therapies will be required. Adding colesevelam, ezetimibe, or niacin to a stable statin regimen will generally provide an additional 10% to 15% lowering of plasma LDL cholesterol. These more potent statins, even when used in higher doses, appear to be safe. The incidence of myopathy and rhabdomyolysis, as documented in long-term clinical trials, is <0.1% and <0.01%, respectively, except for simvastatin, which has a higher incidence of these problems. Less information is available about the safety of lowering levels of plasma LDL cholesterol to < or = 1.81 mmol/L (< or = 70 mg/dL), but an analysis of a recent 2-year-long clinical trial, in which patients had on-treatment plasma LDL cholesterol levels as low as 0.67 mmol/L (26 mg/dL), reported no signals of untoward effects in patients with progressively lower levels.

Allylamine↗
PubMed2005

Results of the National Cholesterol Education (NCEP) Program Evaluation ProjecT Utilizing Novel E-Technology (NEPTUNE) II survey and implications for treatment under the recent NCEP Writing Group recommendations.

The most recent national survey of compliance with the National Cholesterol Education Program (NCEP) Adult Treatment Panel (ATP) guidelines was completed before ATP III and showed significant underachievement of low-density lipoprotein (LDL) cholesterol goals. The NCEP Evaluation ProjecT Utilizing Novel E-Technology (NEPTUNE) II was a national survey conducted in 2003. Of the 4,885 patients, 67% achieved their LDL cholesterol treatment goal, including 89%, 76%, and 57%, respectively, in the 0 or 1 risk factor, > or = 2 risk factors or coronary heart disease (CHD), and CHD risk equivalent categories. The percentage with triglyceride concentrations > or = 200 mg/dl (2.25 mmol/L) in each risk category who achieved their LDL cholesterol and non-high-density lipoprotein cholesterol goals was 64%, 52%, and 27%, respectively. Patients with diabetes (55%) and other CHD risk equivalents (40%) were less likely to have achieved their LDL cholesterol targets than those with CHD (62%). Of the 1,447 patients with cardiovascular disease, 75% could be classified as very high risk according to the new July 2004 NCEP Writing Group recommendations, and 17.8% of those at very high risk had an LDL cholesterol level of <70 mg/dl (<1.81 mmol/L). In conclusion, these results suggest improved lipid management compared with previous surveys. The largest treatment gaps were found for features new to ATP III as of July 2004, including goal achievement for patients with CHD risk equivalents and for non-high-density lipoprotein cholesterol targets. Most of those (75%) with cardiovascular disease in NEPTUNE II would be considered very high risk and candidates for aggressive therapy to reach the new optional treatment goals.

Anticholesteremic Agents↗
PubMed2005

Efficacy and safety of rosuvastatin in treatment of dyslipidemia.

PURPOSE: The chemistry, pharmacology, pharmacokinetics, drug interactions, clinical efficacy, adverse effects, dosage and administration, and place in therapy of rosuvastatin are reviewed. SUMMARY: Rosuvastatin, the latest statin to receive approved labeling by the Food and Drug Administration, has shown superior efficacy in lowering low-density-lipoprotein (LDL) cholesterol. At daily doses of 5-40 mg, rosuvastatin produces mean reductions in plasma LDL cholesterol of 45-63%, statistically greater than those achieved with equivalent doses of atorvastatin, simvastatin, and pravastatin. Rosuvastatin also improves triglyceride, non-high-density lipoprotein (HDL)-cholesterol, and HDL cholesterol levels to produce a more favorable lipid profile. Rosuvastatin's safety was studied in more than 10,000 patients, exceeding the number of patients evaluated before the launch of any other statin. Many of these patients took the drug for up to 96 weeks. With regard to muscle, renal, and hepatic toxicity and the withdrawal rate due to adverse events, rosuvastatin demonstrates a safety profile similar to that of the other marketed statins. Rosuvastatin undergoes only minor metabolism (10% of the administered dose) by the cytochrome P-450 2C9 isoenzyme. Significant drug interactions were reported with cyclosporine, gemfibrozil, warfarin, and antacids. Evidence suggests that rosuvastatin will be a valuable addition to the choices for treatment of patients with dyslipidemia. CONCLUSION: Rosuvastatin has greater efficacy in lowering LDL cholesterol and non-HDL-cholesterol concentrations than the other statins. It has been shown to enable more patients to reach their LDL cholesterol goals than other statins and to do so with an acceptable safety profile.

Cholesterol, HDL↗
PubMed2005

Comparison of the efficacy and safety of atorvastatin initiated at different starting doses in patients with dyslipidemia.

BACKGROUND: The NASDAC study was designed to evaluate the safety and efficacy of atorvastatin at starting doses of 10, 20, 40, and 80 mg. METHODS: After an 8-week placebo washout period, 919 patients who were candidates for lipid-lowering therapy according to the National Cholesterol Education Program's Adult Treatment Panel III guidelines were randomized to 1 of 4 atorvastatin treatment groups: 10 mg (n = 229), 20 mg (n = 228), 40 mg (n = 231), and 80 mg (n = 231). RESULTS: Atorvastatin reduced low-density lipoprotein cholesterol (LDL-C) levels dose dependently across the 10- to 80-mg-dose range (35.7%-52.2%). Each of the 20-, 40-, and 80-mg doses provided significantly greater decreases in LDL-C than all lower doses (P < .01). All doses also reduced total cholesterol, the LDL-C/high-density lipoprotein cholesterol ratio, apolipoprotein B, and triglycerides from baseline. An increase in high-density lipoprotein cholesterol was observed in all dose groups. Most participants, regardless of their level of coronary heart disease risk, attained their National Cholesterol Education Program's Adult Treatment Panel III LDL-C goal by the end of the study. Patients in all risk groups were more likely to achieve the NCEP LDL-C goal at higher starting doses. Atorvastatin was well tolerated at all dose levels. CONCLUSIONS: Atorvastatin initiated at doses of 10, 20, 40, and 80 mg is effective and safe for the treatment of patients with dyslipidemia. Depending on the percentage reduction needed to achieve an LDL-C goal, patients with or at risk of coronary heart disease may benefit from starting therapy at a higher dose of atorvastatin.

Adult↗
PubMed2005

Use of a treatment algorithm to achieve NCEP ATP III goals with atorvastatin.

This multicenter, 8-week, single-step titration, open-label study sought to assess the percentage of subjects who achieved their National Cholesterol Education Program Adult Treatment Panel (NCEP ATP) III low-density lipoprotein (LDL)-cholesterol target when assigned a starting dose of atorvastatin (10 mg, 20 mg, 40 mg, or 80 mg) selected using an algorithm based on their 10-year CHD risk and the magnitude of LDL-cholesterol lowering necessary to reach goal. Following an 8-week washout period, 1298 subjects, categorized as low, medium, or high risk, were assigned to 4 weeks of treatment with a starting dose of atorvastatin selected by the algorithm. At week 4, subjects who did not achieve goal (15.8%) were titrated to the next-higher dose. The primary endpoint was the percentage of subjects in each risk group who achieved LDL-cholesterol goal at week 8. At 8 weeks, 84.8% of subjects (low risk 92.9%; moderate risk 84.0%; high risk 81.1%) achieved LDL-cholesterol target. The majority of patients (84.2%) achieved their lipid target through the use of the algorithm-based starting dose (10-80 mg) without the need for titration. No patient had elevations in creatine phosphokinase >10 times the upper limit of normal. Elevations in alanine aminotransaminase or aspartate aminotransaminase were observed in <1% of study subjects and were unrelated to dose. Selecting the starting dose of atorvastatin using a treatment algorithm achieves NCEP ATP III LDL-cholesterol goals in the majority of patients and minimizes the need for dose titration.

Adolescent↗
PubMed2004

Understanding physician and consumer attitudes concerning cholesterol management: results from the National Lipid Association surveys.

Two online surveys commissioned by the National Lipid Association (NLA) were conducted to determine the current attitudes of physicians and consumers regarding cholesterol and heart disease. Physicians and consumers from preexisting independent panels were randomly invited to participate in the online surveys that were open from January 26 to 30, 2004. Both physicians (n = 200) and consumers (n = 600) agreed that high cholesterol and coronary artery disease (CAD) are significant health risks. Physicians reported the primary barriers for patients being prescribed cholesterol-lowering medication as patient fear of side effects (61%) and reluctance to take prescription medications (52%). While most physicians were aware of and felt they adhered to the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) guidelines, considerably fewer thought the same of other physicians. The consumer survey focused on untreated moderate-risk patients (an approximate 10% to 20% 10-year risk of myocardial infarction and cardiac death) because this group is often undertreated. Untreated moderate-risk patients reported that their physicians did not advise them to take prescription cholesterol-lowering drugs (51%) and that they were trying to control their cholesterol with diet and exercise (58%). Consumers believe they are taking an increased role in their own health management and decision making. Current attitudes of physicians and consumers are similar with regard to their recognition of the significance of cholesterol and CAD for health, but differ with regard to why patients do not take prescription medications.

Adult↗
PubMed2004

The National Lipid Association surveys of consumers, physicians, and pharmacists regarding an over-the-counter statin in the United States: is this a good idea?

Surveys commissioned by the National Lipid Association (NLA) were conducted to determine the current attitudes and perceptions of physicians, consumers, and pharmacists regarding the impact of an over-the-counter (OTC) statin. Individuals from preexisting independent databases were randomly invited to participate in the online surveys that were open from January 26 to 30, 2004 for physicians and consumers and from March 1 to 12, 2004 for pharmacists. The results of these surveys indicate that consumers and pharmacists are more positive regarding the idea of an OTC statin, whereas physicians are more guarded. Concerns of both physicians and pharmacists included the discontinuation by patients of their prescription cholesterol-lowering therapy without consulting their physician, safety issues such as potential drug interactions and side effects, and patient ability to self-manage OTC statins. Consumers interested in purchasing an OTC statin reported that they would consult their physician before doing so, and pharmacists were interested in supporting consumers who use OTC statins. Although such support would require further training and time, pharmacists believed that they could facilitate consumer self-care programs and follow-up with physicians.

Anticholesteremic Agents↗
PubMed2003

Effectiveness and tolerability of a new lipid-altering agent, gemcabene, in patients with low levels of high-density lipoprotein cholesterol.

This study evaluated the efficacy and tolerability of gemcabene, a new lipid-altering agent, in a double-blind, randomized, dose-response study of 161 patients with high-density lipoprotein (HDL) cholesterol of <35 mg/dl and serum triglyceride (TG) levels of either >/=200 (n = 94) or <200 mg/dl (n = 67). After a 6-week, placebo, dietary lead-in period, patients were administered either 150, 300, 600, or 900 mg of gemcabene or placebo once daily for 12 weeks. In the TG >/=200 mg/dl stratum, gemcabene significantly increased serum HDL cholesterol by 18% with corresponding significant increases of 6% in both apolipoprotein A-I and A-II levels at the 150-mg dose. HDL cholesterol levels also increased 12% at the 300-mg dose; however, this did not reach statistical significance. Also, in the TG >/=200 mg/dl stratum, serum TG levels were significantly reduced by 27% and 39% at the 150- and 300-mg doses of gemcabene, respectively. No significant differences were found in serum HDL cholesterol or TG levels in the TG >/=200 mg/dl groups that received 600 or 900 mg of gemcabene, or in TG <200 mg/dl groups administered any dose of gemcabene. However, at these higher 600- and 900-mg doses, gemcabene significantly reduced serum low-density lipoprotein (LDL) cholesterol levels by 15% to 25%, respectively, in both TG strata, with proportionate decreases in the levels of apolipoprotein B. Gemcabene was well tolerated with a frequency of adverse events similar to that of placebo. In conclusion, at the lower doses, gemcabene significantly increased HDL cholesterol and reduced TG serum levels in patients with low HDL cholesterol and TG >/=200 mg/dl. At the higher doses, gemcabene significantly reduced LDL cholesterol levels in all patients with low HDL cholesterol.

Aged↗
PubMed2003

Comparison of the efficacy and safety of rosuvastatin versus atorvastatin, simvastatin, and pravastatin across doses (STELLAR* Trial).

The primary objective of this 6-week, parallel-group, open-label, randomized, multicenter trial was to compare rosuvastatin with atorvastatin, pravastatin, and simvastatin across dose ranges for reduction of low-density lipoprotein (LDL) cholesterol. Secondary objectives included comparing rosuvastatin with comparators for other lipid modifications and achievement of National Cholesterol Education Program Adult Treatment Panel III and Joint European Task Force LDL cholesterol goals. After a dietary lead-in period, 2,431 adults with hypercholesterolemia (LDL cholesterol > or =160 and <250 mg/dl; triglycerides <400 mg/dl) were randomized to treatment with rosuvastatin 10, 20, 40, or 80 mg; atorvastatin 10, 20, 40, or 80 mg; simvastatin 10, 20, 40, or 80 mg; or pravastatin 10, 20, or 40 mg. At 6 weeks, across-dose analyses showed that rosuvastatin 10 to 80 mg reduced LDL cholesterol by a mean of 8.2% more than atorvastatin 10 to 80 mg, 26% more than pravastatin 10 to 40 mg, and 12% to 18% more than simvastatin 10 to 80 mg (all p <0.001). Mean percent changes in high-density lipoprotein cholesterol in the rosuvastatin groups were +7.7% to +9.6% compared with +2.1% to +6.8% in all other groups. Across dose ranges, rosuvastatin reduced total cholesterol significantly more (p <0.001) than all comparators and triglycerides significantly more (p <0.001) than simvastatin and pravastatin. Adult Treatment Panel III LDL cholesterol goals were achieved by 82% to 89% of patients treated with rosuvastatin 10 to 40 mg compared with 69% to 85% of patients treated with atorvastatin 10 to 80 mg; the European LDL cholesterol goal of <3.0 mmol/L was achieved by 79% to 92% in rosuvastatin groups compared with 52% to 81% in atorvastatin groups. Drug tolerability was similar across treatments.

Adult↗