Rebecca Bakker-Arkema

Comparison of One-Year Efficacy and Safety of Atorvastatin Versus Lovastatin in Primary Hypercholesterolemia

This double-blind study to evaluate long-term efficacy and safety of atorvastatin was performed in 31 community- and university-based research centers in the USA to directly compare a new 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor (reductase inhibitor) to an accepted drug of this class in patients with moderate hypercholesterolemia. Participants remained on a cholesterol-lowering diet throughout the study. One thousand forty-nine patients were randomized to receive atorvastatin 10 mg, lovastatin 20 mg, or placebo. At 16 weeks the placebo group was randomized to either atorvastatin or lovastatin treatment. At 22 weeks, patients who had not met low-density lipoprotein (LDL) cholesterol target levels doubled the dose of reductase inhibitor. Efficacy evaluation was mean percent change from baseline in LDL cholesterol, triglycerides, total cholesterol, high-density-lipoprotein cholesterol, and apolipoprotein B (apoB). Safety profiles as determined by change from baseline in laboratory evaluations, ophthalmologic parameters, and reporting of adverse events were similar for the 2 reductase inhibitors. After 52 weeks, the atorvastatin group maintained a significantly greater reduction in LDL cholesterol (-37% vs -29%), triglyceride (-16% vs -8%), total cholesterol (-27% vs -21%), and apoB (-30% vs -22%) (p <0.05). More patients receiving atorvastatin achieved LDL cholesterol target levels than did lovastatin patients (78% vs 63%, respectively), particularly those with coronary heart disease (37% vs 11%, respectively). Atorvastatin is highly effective and well tolerated in patients with primary hypercholesterolemia with no increased risk of adverse events.

Treating patients with documented atherosclerosis to national cholesterol education program-recommended low-density-lipoprotein cholesterol goals with atorvastatin, fluvastatin, lovastatin and simvastatin ☆

OBJECTIVES This study compared the efficacy and safety of atorvastatin, fluvastatin, lovastatin, and simvastatin in patients with documented atherosclerosis treated to U.S. National Cholesterol Education Program (NCEP) recommended low-density-lipoprotein (LDL) cholesterol concentration (< or = 100 mg/dl [2.59 mmol/liter]). BACKGROUND For patients with advanced atherosclerosis, NCEP recommends lipid-lowering drug therapy if LDL cholesterol remains > or = 130 mg/dl (3.36 mmol/liter). METHODS A total of 318 men or women with documented atherosclerosis and LDL cholesterol > or = 130 mg/dl (3.36 mmol/liter) and < or = 250 mg/dl (6.5 mmol/liter), and triglycerides < or = 400 mg/dl (4.5 mmol/liter) participated in this 54-week, multicenter, open-label, randomized, parallel-group, active-controlled, treat-to-target study. Patients were titrated at 12-week intervals until the LDL cholesterol goal was reached. Number of patients reaching target LDL cholesterol levels and dose to reach target were evaluated. RESULTS At the starting doses, atorvastatin 10 mg produced significantly greater decreases (p < 0.05) in plasma LDL cholesterol than the other treatments. Subsequently, the percentage of patients reaching goal at the starting dose was 32% for atorvastatin, 1% for fluvastatin, 10% for lovastatin and 22% for simvastatin. Atorvastatin-treated patients required a lower median dose than other treatments. Median doses at week 54 with the last available visit carried forward were atorvastatin 20 mg/day, fluvastatin 40 mg/day + colestipol 20 g/day, lovastatin 80 mg/day, simvastatin 40 mg/day. CONCLUSIONS A significantly greater number (p < 0.05) of patients with confirmed atherosclerosis treated with atorvastatin reached the target LDL cholesterol concentration at the starting dose than patients treated with fluvastatin or lovastatin, and significantly fewer (p < 0.05) patients treated with atorvastatin required combination therapy with colestipol to achieve target LDL cholesterol concentrations than all other statins tested.

Apolipoprotein E genotype affects plasma lipid response to atorvastatin in a gender specific manner

The response to therapy with hypolipidemic agents shows considerable individual variation. These differences may be due to the interaction of environmental and genetic factors that affect drug bioavailability, receptor function or ligand structure. Our objective was to assess the effect of apolipoprotein (apo) E genotype and gender on lipid-lowering response to the HMG CoA reductase inhibitor, atorvastatin. Genotyping was carried out on DNA from 328 male and female subjects who participated in a multicentric, double-blind clinical trial, and received 10 mg/day of atorvastatin. Our data demonstrate no significant gender differences for LDL cholesterol levels at baseline. Moreover, mean LDL-C lowering was similar in men (-36.2%, range -2.7 to -57.8%) and in women (-38.1%, range -9.5 to -58.5%) as compared to baseline. However, men carrying the epsilon2 allele had a significantly higher mean LDL-C response (-44%) than epsilon3 homozygotes (-37%) and epsilon4 carriers (-34%); P=0.01 for apoE group by treatment interaction. No such gene/treatment interactions were noted in women, with those carrying the epsilon2 allele showing a similar mean response (-34%) as epsilon3 homozygotes (-39%) and epsilon4 carriers (-34%). Mean plasma triglyceride lowering with atorvastatin was 17%. A significant apoE group by treatment interaction (P=0.010) was also observed in men, with epsilon2 carriers being more responsive (-27%) than epsilon3/3 (-13%) and epsilon4 (-22%). This interaction was not observed in women. In summary, atorvastatin treatment had similar effects on plasma lipid levels in both men and women; however, the apoE gene locus was a significant predictor of LDL-C and TG responses to atorvastatin therapy in men, but not in women.

The Cost of Reaching National Cholesterol Education Program (NCEP) Goals in Hypercholesterolaemic Patients A Comparison of Atorvastatin, Simvastatin, Lovastatin and Fluvastatin

AbstractObjective: 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 [

Safety profile of atorvastatin-treated patients with low LDL-cholesterol levels

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A brief review paper of the efficacy and safety of atorvastatin in early clinical trials

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Atorvastatin, a New HMG-CoA Reductase Inhibitor, Does Not Affect Glucocorticoid Hormones in Patients With Hypercholesterolemia.

US1176] compared with simvastatin (

The Effect of Atorvastatin on the Human Lens After 52 Weeks of Treatment

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EFFECT OF GEMCABENE ON INSULIN SENSITIVITY IN NONDIABETIC, OBESE SUBJECTS

US1304 to

Efficacy and Safety of a New HMG-CoA Reductase Inhibitor, Atorvastatin, in Patients With Hypertriglyceridemia

US1648), lovastatin (