Reduction of LDL Cholesterol by 25% to 60% in Patients With Primary Hypercholesterolemia by Atorvastatin, a New HMG-CoA Reductase Inhibitor

Nawrocki, J.W.; Weiss, Stuart; Davidson, Michael; Sprecher, Dennis L.; Schwartz, Sherwyn; Lupien, Paul J.; Jones, Peter H.; Haber, Harry; Black, Donald M.

doi:10.1161/01.atv.15.5.678

Cited by 429 publications

(174 citation statements)

References 14 publications

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“…In our study, 59.1% of patients whose disease was previously uncontrolled with other statins met the SEA LDL-C goals at visit 3. The mean percentages of reduction in LDL-C, TC, and TG levels in our study were within the range reported in a previous double-blind clinical trial, 14 but with a higher increase in HDL-C levels. Our study showed significant differences in the mean percentages of reduction in LDL-C in all risk groups, which confirms the overall effectiveness of atorvastatin.…”

Section: Discussionsupporting

confidence: 89%

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A six-month, multicenter, open-label, noncomparative, prospective, observational study of the efficacy and tolerability of atorvastatin in the primary care setting(estudio del control de las hiperlipidemiasen atención primaria): the cheap study

Gómez-Gerique

Álvarez-Sala

Armada

et al. 2003

Current Therapeutic Research

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Background: A close relationship exists between high levels of total cholesterol (TC) (particularly low-density lipoprotein cholesterol [LDL-C]) and low levels of high-density lipoprotein cholesterol (HDL-C), which is associated with an increased risk for arteriosclerosis and cardiovascular disease (CVD). Evidence shows that atorvastatin produces significantly greater reductions in LDL-C and TC than other hydroxymethylglutaryl-coenzyme A reductase inhibitors. However, the results achieved in clinical studies could be different from those found in general clinical practice, where patient follow-up is less thorough and poorer compliance may reduce the effectiveness of the lipid-lowering therapy.Objective: The aim of this study was to assess the effectiveness of atorvastatin in achieving the LDL-C levels recommended by several Spanish scientific societies, as well as its tolerability in standard clinical use.Methods: This 6-month, open-label, noncomparative, prospective, observational study was conducted in 1351 primary care centers in Spain. All patients were aged 18 to 80 years and had primary hypercholesterolemia (TC Ͼ200 mg/ dL and triglycerides [TG] Ͻ200 mg/dL) or combined hyperlipidemia (TC Ͼ200 mg/dL and fasting TG 200-400 mg/dL). All patients also had LDL-C levels higher than those established by the Spanish Society of Arteriosclerosis (Sociedad Española de Arteriosclerosis [SEA]) according to baseline cardiovascular risk and previous use of lipid-lowering therapy (for patients with low, moderate, or high cardiovascular risk, the recommended LDL-C goals are Յ175 mg/dL, Յ155Accepted for publication February 13, 2003. doi:10.1016/S0011-393X(03)00090-0 Reproduction in whole or part is not permitted.0011-393X/03/$19.00 338Copyright ą 2003 Excerpta Medica, Inc. J.A. Gómez-Gerique et al.mg/dL, and Յ135 mg/dL, respectively; for patients with CVD, the LDL-C goal is Յ100 mg/dL). None of the patients had creatine kinase activity Ն540 U/L or alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels Ն60 U/L. Study visits occurred at months 0, 2, and 6 of treatment. Patients received atorvastatin calcium 10 mg/d for 2 months. The dosage was then doubled to 20 mg/d in patients who did not achieve the SEA LDL-C goal and also in those patients whose primary care physicians (PCPs) deemed this higher dosage necessary; this dosage was continued for at least 4 additional months, to complete at least a 6-month course of treatment. The percentage of patients who achieved their goals was used to measure atorvastatin effectiveness. Percentages of change in LDL-C, TC, TG, and HDL-C from baseline to the final study visit also were used as measures of effectiveness. The incidence of adverse events (AEs) per 10,000 patient-months was used for the primary tolerability analysis. A secondary tolerability analysis was performed in all patients treated with atorvastatin who had some recorded follow-up, regardless of whether the patient met inclusion criteria. Information was obtained from data recorded in the case...

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Section: Discussionsupporting

confidence: 89%

“…13 In placebo-controlled, dose-response studies 14 in patients with primary hypercholesterolemia, atorvastatin produced 25% to 60% reductions in LDL-C levels. When given in equivalent doses (in milligrams), atorvastatin produced significantly greater reductions in LDL-C and TC than other HMG-CoA reductase inhibitors.…”

Section: Introductionmentioning

confidence: 99%

A six-month, multicenter, open-label, noncomparative, prospective, observational study of the efficacy and tolerability of atorvastatin in the primary care setting(estudio del control de las hiperlipidemiasen atención primaria): the cheap study

Gómez-Gerique

Álvarez-Sala

Armada

et al. 2003

Current Therapeutic Research

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“…1,2 Atorvastatin is the most efficacious of the currently available HMG-CoA reductase inhibitors in terms of its LDL cholesterol-lowering effect. 3,4 In addition, it has a modest triglyceride-lowering action. 3 More recently, the importance of drug therapy on HDL metabolism has been recognized.…”

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confidence: 99%

Effect of Atorvastatin on High-Density Lipoprotein Apolipoprotein A-I Production and Clearance in the New Zealand White Rabbit

et al. 2002

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Background-HMG-CoA reductase inhibitors reduce the incidence of cardiovascular disease predominantly by their LDL-lowering effect. Recently, there has been great interest in the pleiotropic effects of statins, which appear to differ among the various agents in this class. Unlike other statins, atorvastatin exhibits a decline in its HDL-raising effect at higher doses in humans. Whether atorvastatin-mediated alterations in HDL turnover in vivo contribute to this effect has not previously been investigated. We therefore studied the effect of atorvastatin on HDL apolipoprotein (apo) A-I production and clearance in normolipidemic male New Zealand White rabbits. Methods and Results-Kinetic studies of HDL-apoA-I radiolabeled with 131 I were performed in chow-fed rabbits after 3 weeks of atorvastatin treatment of 5 mg · kg Ϫ1 · d Ϫ1 (nϭ7) versus placebo-treated rabbits (nϭ7). Our results showed a significantly (PϽ0.001) more rapid clearance (Ϸ2-fold) of HDL apoA-I in atorvastatin-treated animals compared with the control group (0.121Ϯ0.012 versus 0.061Ϯ0.004 pools/h, respectively), accompanied by a lesser 48% increase in the apoA-I production rate (3.84Ϯ0.38 versus 2.59Ϯ0.41 mg · kg Ϫ1 · h

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“…31,32 Clinical trials of atorvastatin in humans have demonstrated marked plasma LDL cholesterol and triglyceride reductions. [33][34][35] We have previously shown in vivo that inhibition of HMG-CoA reductase by atorvastatin in miniature pigs significantly decreases hepatic apoB-containing lipoprotein secretion into plasma in the fasting state, 36 with minimal effect on rate of clearance. We have now developed a multicompartmental model of TRL metabolism and have used kinetic analysis to determine the metabolic parameters of postprandial exogenous TRL in plasma with atorvastatin treatment.…”

mentioning

confidence: 99%

The HMG-CoA Reductase Inhibitor Atorvastatin Increases the Fractional Clearance Rate of Postprandial Triglyceride-Rich Lipoproteins in Miniature Pigs

Burnett

Barrett

Vicini

et al. 1998

ATVB

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Abstract-We have previously shown in vivo that the 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor atorvastatin decreases hepatic apolipoprotein B (apoB) secretion into plasma. To test the hypothesis that atorvastatin modulates exogenous triglyceride-rich lipoprotein (TRL) metabolism in vivo, an oral fat load (2 g fat/kg body wt) containing retinol (50 000 IU) was given to 6 control miniature pigs and to 6 animals after 28 days of treatment with atorvastatin 3 mg ⅐ kg Ϫ1 ⅐ d Ϫ1. A multicompartmental model was developed by use of SAAM II and kinetic analysis performed on the plasma retinyl palmitate (RP) data. Peak TRL (dϽ1.006 g/mL; S f Ͼ20) triglyceride concentrations were decreased 29% by atorvastatin, and the time to achieve this peak was delayed (5.2 versus 2.3 hours; PϽ0.01). The TRL triglyceride 0-to 12-hour area under the curve was decreased by 24%. In contrast, atorvastatin treatment had no effect on peak TRL RP concentrations, time to peak, or its rate of appearance into plasma; however, the TRL RP 0-to 12-hour area under the curve was decreased by 20%. Analysis of the RP kinetic parameters revealed that the TRL fractional clearance rate was increased significantly, 1.4-fold (3.093 versus 2.276 pools/h; Pϭ0.012), with atorvastatin treatment. The percent conversion of TRL RP from the rapid-turnover to the slow-turnover compartment was decreased by 47% with atorvastatin treatment. The TRL RP fractional clearance rate was negatively correlated with very low density lipoprotein apoB production rate measured in the fasting state (rϭϪ0.49). Thus, although atorvastatin had no effect on intestinal TRL assembly and secretion, plasma TRL clearance was significantly increased, an effect that may relate to a decreased competition for removal processes by hepatic very low density lipoprotein.

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Reduction of LDL Cholesterol by 25% to 60% in Patients With Primary Hypercholesterolemia by Atorvastatin, a New HMG-CoA Reductase Inhibitor

Cited by 429 publications

References 14 publications

A six-month, multicenter, open-label, noncomparative, prospective, observational study of the efficacy and tolerability of atorvastatin in the primary care setting(estudio del control de las hiperlipidemiasen atención primaria): the cheap study

A six-month, multicenter, open-label, noncomparative, prospective, observational study of the efficacy and tolerability of atorvastatin in the primary care setting(estudio del control de las hiperlipidemiasen atención primaria): the cheap study

Effect of Atorvastatin on High-Density Lipoprotein Apolipoprotein A-I Production and Clearance in the New Zealand White Rabbit

The HMG-CoA Reductase Inhibitor Atorvastatin Increases the Fractional Clearance Rate of Postprandial Triglyceride-Rich Lipoproteins in Miniature Pigs

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