Combined therapy in the treatment of dyslipidemia

Reiner, Željko

doi:10.1111/j.1472-8206.2009.00764.x

Cited by 84 publications

(43 citation statements)

References 107 publications

(106 reference statements)

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“…The therapeutic needs of these patients are likely to exceed LDL-C lowering by statin monotherapy. 239 The recommended steps for managing these patients after achieving LDL-C goal, as defined by the most recent European guidelines, 4 are summarized in Figure 6. The Panel proposes triglycerides as a marker for TRL and their remnants.…”

Section: Guidance For Clinical Managementmentioning

confidence: 99%

32 Triglyceride-Rich Lipoproteins and High-Density Lipoprotein Cholesterol in Patients at High Risk of Cardiovascular Disease: Evidence and Guidance for Management

Chapman¹,

Ginsberg²,

Amarenco³

et al. 2011

Atherosclerosis Supplements

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Even at low-density lipoprotein cholesterol (LDL-C) goal, patients with cardiometabolic abnormalities remain at high risk of cardiovascular events. This paper aims (i) to critically appraise evidence for elevated levels of triglyceride-rich lipoproteins (TRLs) and low levels of highdensity lipoprotein cholesterol (HDL-C) as cardiovascular risk factors, and (ii) to advise on therapeutic strategies for management. Current evidence supports a causal association between elevated TRL and their remnants, low HDL-C, and cardiovascular risk. This interpretation is based on mechanistic and genetic studies for TRL and remnants, together with the epidemiological data suggestive of the association for circulating triglycerides and cardiovascular disease. For HDL, epidemiological, mechanistic, and clinical intervention data are consistent with the view that low HDL-C contributes to elevated cardiovascular risk; genetic evidence is unclear however, potentially reflecting the complexity of HDL metabolism. The Panel believes that therapeutic targeting of elevated triglycerides (≥1.7 mmol/L or 150 mg/dL), a marker of TRL and their remnants, and/or low HDL-C (,1.0 mmol/L or 40 mg/dL) may provide further benefit. The first step should be lifestyle interventions together with consideration of compliance with pharmacotherapy and secondary causes of dyslipidaemia. If inadequately corrected, adding niacin or a fibrate, or intensifying LDL-C lowering therapy may be considered. Treatment decisions regarding statin combination therapy should take into account relevant safety concerns, i.e. the risk of elevation of blood glucose, uric acid or liver enzymes with niacin, and myopathy, increased serum creatinine and cholelithiasis with fibrates. These recommendations will facilitate reduction in the substantial cardiovascular risk that persists in patients with cardiometabolic abnormalities at LDL-C goal.--

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Section: Guidance For Clinical Managementmentioning

confidence: 99%

32 Triglyceride-Rich Lipoproteins and High-Density Lipoprotein Cholesterol in Patients at High Risk of Cardiovascular Disease: Evidence and Guidance for Management

Chapman¹,

Ginsberg²,

Amarenco³

et al. 2011

Atherosclerosis Supplements

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“…Dyslipidemia, broadly characterized by elevated circulating levels of low-density lipoprotein-cholesterol (LDL-C) and triglycerides (TG), is commonly treated by therapeutic intervention at the level of hepatic function (Reiner, 2010).…”

Section: Introductionmentioning

confidence: 99%

A Small-Molecule Inhibitor of Enterocytic Microsomal Triglyceride Transfer Protein, SLx-4090: Biochemical, Pharmacodynamic, Pharmacokinetic, and Safety Profile

Kim¹,

Campbell²,

Schueller³

et al. 2011

J Pharmacol Exp Ther

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First-generation microsomal triglyceride transfer protein (MTP) inhibitors were designed to inhibit hepatic MTP and provide a novel treatment of dyslipidemia. Effective at lowering low-density lipoprotein-cholesterol (LDL-C), these inhibitors also elevate liver enzymes and induce hepatic steatosis in animals and humans. MTP is highly expressed in the enterocytes, lining the lumen of the jejunum, and is critical in the production of chylomicrons assembled from lipid/cholesterol and their transfer into systemic circulation. 6-(4Ј-Trifluoromethyl-6-methoxy-biphenyl-2-ylcarboxamido)-1,2,3,4-tetrahydroisoquinoline-2-carboxylic acid phenyl ester (SLx-4090) (IC 50 value ϳ8 nM) was designed to inhibit only MTP localized to enterocytes. In Caco-2 cells SLx-4090 inhibited apolipoprotein B (IC 50 value ϳ9.6 nM) but not apolipoprotein A1 secretion. Administered orally to rats SLx-4090 reduced postprandial lipids by Ͼ50% with an ED 50 value ϳ7 mg/kg. SLx-4090 was not detected in the systemic or portal vein serum of the animals (lower limit of quantitation ϳ5 ng/ml) after single or multiple oral doses in fasted rodents. When coadministered with tyloxapol, SLx-4090 did not inhibit the secretion of hepatic triglycerides (TG), consistent with the absence of systemic exposure. Chronic treatment with SLx-4090 in mice maintained on a high-fat diet decreased LDL-C and TG and resulted in weight loss without the elevation of liver enzymes or an increase in hepatic fat. The compound did not result in toxicity when administered to rats for 90 days at a dose of 1000 mg/kg per day. These data support the concept that the inhibition of enterocytic MTP could serve as a useful strategy in the treatment of metabolic disorders.

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“…Другое преимущество комбинированной тера-пии -это возможность назначения низких дозы стати-нов, что устраняет возможный риск неблагоприятных эффектов, связанный с применением высоких доз ста-тинов . Однако, перед назначением комбинации препа-ратов статины следует назначать в максимально перено-симых дозах с целью достижения целевого уровня ХС-ЛПНП [500] .…”

Section: комбинации лекарственных препаратовunclassified

A Ten Year Overview of Surgical and Interventional Arrhythmology in Russia. Service Peculiar Features in the Far East

Богачевская¹,

Bogachevskiy²

2017

Soc.Asp.Pop.Hlth

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Combined therapy in the treatment of dyslipidemia

Cited by 84 publications

References 107 publications

32 Triglyceride-Rich Lipoproteins and High-Density Lipoprotein Cholesterol in Patients at High Risk of Cardiovascular Disease: Evidence and Guidance for Management

32 Triglyceride-Rich Lipoproteins and High-Density Lipoprotein Cholesterol in Patients at High Risk of Cardiovascular Disease: Evidence and Guidance for Management

A Small-Molecule Inhibitor of Enterocytic Microsomal Triglyceride Transfer Protein, SLx-4090: Biochemical, Pharmacodynamic, Pharmacokinetic, and Safety Profile

A Ten Year Overview of Surgical and Interventional Arrhythmology in Russia. Service Peculiar Features in the Far East

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