The efficacy of simvastatin in patients with hypertriglyceridemia

Isaacsohn, Jonathan L.; Hunninghake, Donald B.; Schrott, H.A.; Dujovne, C.A.; Knopp, Robert H.; Weiss, Stuart; Bays, Harold; Crouse, John R.; Davidson, Michael; Samuel, Paul; Keilson, Leonard; McKenney, J.; Korenman, Stanley G.; Dobs, Adrian S.; Laskarzewski, Peter M.; Liu, M.; Plotkin, D.; Mitchel, Yale

doi:10.1016/s0021-9150(99)80149-x

Cited by 2 publications

(3 citation statements)

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“…Atorvastatin has previously been shown to reduce fasting cholesterol content in large, medium, and small LDL particles by 45%, 33%, and 47%, respectively; increase cholesterol in large HDL particles by 37%; and reduce triglycerides in large, medium, and small VLDL particles by 39%, 35%, and 59%, respectively 22 . In patients with hypertriglyceridemia, simvastatin has been shown to reduce all LDL subclasses similarly, with a trend toward improved efficacy on small, dense LDL particles at the highest dose (80 mg), where the greatest reductions in triglyceride levels were also found 23 . Other studies have demonstrated that simvastatin, 24 pravastatin, 25 and fluvastatin 26 uniformly affected various lipoprotein subclasses in a proportional way and had minimal, if any, effects on the distribution ratios of lipoprotein subclasses in hypercholesterolemic patients.…”

Section: Discussionmentioning

confidence: 99%

Once‐Daily Niacin Extended Release/Lovastatin Combination Tablet Has More Favorable Effects on Lipoprotein Particle Size and Subclass Distribution Than Atorvastatin and Simvastatin

Bays

McGovern²,

Kopin³

2003

Preventive Cardiology

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Standard lipoprotein measurements may not adequately reflect the increased atherogenic risk found in patients with abnormalities in lipoprotein particle size and subfraction distribution such as disproportionate amounts of small, dense low-density lipoprotein particles, small high-density lipoprotein particles, or large very-low-density lipoprotein particles. Measurement or anticipation of patients most susceptible to lipoprotein subfraction abnormalities may influence therapeutic choices for the optimal management of dyslipidemia. Previously, the ADvicor Vs. Other Cholesterol-modulating Agents Trial Evaluation demonstrated that niacin extended release/lovastatin provided greater global improvement in lipid parameters such as low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, lipoprotein (a), apolipoprotein B, and apolipoprotein A-I blood levels compared with atorvastatin and simvastatin monotherapies. In this report, niacin extended release/lovastatin was also more effective than atorvastatin and simvastatin monotherapies in reducing small, dense low-density lipoprotein particles and improving low-density lipoprotein phenotype pattern at relative starting doses, and was more effective in increasing the proportion of high-density lipoprotein in the potentially cardioprotective 2b subclass at all doses.

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Section: Discussionmentioning

confidence: 99%

Once‐Daily Niacin Extended Release/Lovastatin Combination Tablet Has More Favorable Effects on Lipoprotein Particle Size and Subclass Distribution Than Atorvastatin and Simvastatin

Bays

McGovern²,

Kopin³

2003

Preventive Cardiology

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show abstract

“…The pharmacodynamics data set consists of 18 studies that reported on plasma LDL-C or changes in plasma LDL-C with simvastatin therapy (see Tab. 2) (Crouse 3rd et al, 1999;Davidson et al, 1997;Geiss et al, 2002;Isaacsohn et al, 2003;Jones et al, 1998;Keech et al, 1994;Kosoglou et al, 2002;Loria et al, 1994;Li et al, 2003;Mölgaard et al, 1988;Mol et al, 1986Mol et al, , 1988Ntanios et al, 1999;Nishio et al, 2005;Owens et al, 1991;Pietro et al, 1989;Recto et al, 2000;Tuomilehto et al, 1994;Walker et al, 1990). Study duration was heterogeneous, ranging from 2 weeks to 3 years, with one study reporting plasma LDL-C after a single dose application (Loria et al, 1994).…”

Section: Database On the Pharmacokinetics And Pharmacodynamics Of Sim...mentioning

confidence: 99%

“…We then used the developed model to predict the reduction in plasma LDL-C with simvastatin therapy (Fig. 6) for data from (Crouse 3rd et al, 1999;Davidson et al, 1997;Geiss et al, 2002;Isaacsohn et al, 2003;Jones et al, 1998;Keech et al, 1994;Kosoglou et al, 2002;Loria et al, 1994;Li et al, 2003;Mölgaard et al, 1988;Mol et al, 1986Mol et al, , 1988Ntanios et al, 1999;Nishio et al, 2005;Owens et al, 1991;Pietro et al, 1989;Recto et al, 2000;Saito et al, 1991;Tuomilehto et al, 1994;Walker et al, 1990).…”

Section: Prediction Of Ldl-c Reduction With Simvastatin Therapymentioning

confidence: 99%

Simvastatin therapy in different subtypes of hypercholesterolemia – a physiologically based modelling approach

Bartsch

Grzegorzewski

Pujol

et al. 2023

Preprint

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Hypercholesterolemia is a multifaceted plasma lipid disorder with heterogeneous causes including lifestyle and genetic factors. A key feature of hypercholesterolemia is elevated plasma levels of low-density lipoprotein cholesterol (LDL-C). Several genetic variants have been reported to be associated with hypercholesterolemia, known as familial hypercholesterolemia (FH). Important variants affect the LDL receptor (LDLR), which mediates the uptake of LDL-C from the plasma, apoliporotein B (APOB), which is involved in the binding of LDL-C to the LDLR, and proprotein convertase subtilisin/kexin type 9 (PCSK9), which modulates the degradation of the LDLR. A typical treatment for hypercholesterolemia is statin medication, with simvastatin being one of the most commonly prescribed statins. In this work, the LDL-C lowering therapy with simvastatin in hypercholesterolemia was investigated using a computational modeling approach. A physiologically based pharmacokinetic model of simvastatin integrated with a pharmacodynamic model of plasma LDL-C (PBPK/PD) was developed based on extensive data curation. A key component of the model is LDL-C turnover by the liver, consisting of: hepatic cholesterol synthesis with the key enzymes HMG-CoA reductase and HMG-CoA synthase; cholesterol export from the liver as VLDL-C; de novo synthesis of LDLR; transport of LDLR to the membrane; binding of LDL-C by LDLR via APOB; endocytosis of the LDLR-LDL-C complex; recycling of LDLR from the complex. The model was applied to study the effects of simvastatin therapy in hypercholesterolemia due to different causes in the LDLR pathway corresponding to different subtypes of hypercholesterolemia. Model predictions of LDL-C lowering therapy were validated with independent clinical data sets. Key findings are: (i) hepatic LDLR turnover is highly heterogeneous among FH classes; (ii) despite this heterogeneity, simvastatin therapy results in a consistent reduction in plasma LDL-C regardless of class; and (iii) simvastatin therapy shows a dose-dependent reduction in LDL-C. Our model suggests that the underlying cause of hypercholesterolemia does not influence simvastatin therapy. Furthermore, our model supports the treatment strategy of stepwise dose adjustment to achieve target LDL-C levels. Both the model and the database are freely available for reuse.

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The efficacy of simvastatin in patients with hypertriglyceridemia

Cited by 2 publications

References 0 publications

Once‐Daily Niacin Extended Release/Lovastatin Combination Tablet Has More Favorable Effects on Lipoprotein Particle Size and Subclass Distribution Than Atorvastatin and Simvastatin

Once‐Daily Niacin Extended Release/Lovastatin Combination Tablet Has More Favorable Effects on Lipoprotein Particle Size and Subclass Distribution Than Atorvastatin and Simvastatin

Simvastatin therapy in different subtypes of hypercholesterolemia – a physiologically based modelling approach

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