Atherogenic lipoprotein phenotype in Type 2 diabetes: reversal with micronised fenofibrate

Feher, Michael; Caslake, Muriel; Foxton, Julie; Cox, Alison; Packard, Christopher J.

doi:10.1002/(sici)1520-7560(199911/12)15:6<395::aid-dmrr65>3.0.co;2-n

Cited by 64 publications

(9 citation statements)

References 29 publications

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“…Patients with diabetes mellitus have dyslipidemia and metabolic complications that contribute to an increased risk of cardiovascular disease (CVD) 1, 2, 3, 4, 5, 6. Statin therapy is the recommended first‐line therapeutic approach for lipid management of high‐risk patients; however, many patients with diabetic dyslipidemia do not achieve adequate low‐density lipoprotein (LDL) cholesterol (LDL‐C) lowering on statin monotherapy 7, 8, 9, 10, 11.…”

Section: Introductionmentioning

confidence: 99%

Effect of Switching From Statin Monotherapy to Ezetimibe/Simvastatin Combination Therapy Compared With Other Intensified Lipid‐Lowering Strategies on Lipoprotein Subclasses in Diabetic Patients With Symptomatic Cardiovascular Disease

Tomassini

Tershakovec

et al. 2015

JAHA

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BackgroundPatients with diabetes mellitus and cardiovascular disease may not achieve adequate low‐density lipoprotein cholesterol (LDL‐C) lowering on statin monotherapy, attributed partly to atherogenic dyslipidemia. More intensive LDL‐C–lowering therapy can be considered for these patients. A previous randomized, controlled study demonstrated greater LDL‐C lowering in diabetic patients with symptomatic cardiovascular disease who switched from simvastatin 20 mg (S20) or atorvastatin 10 mg (A10) to combination ezetimibe/simvastatin 10/20 mg (ES10/20) therapy, compared with statin dose‐doubling (to S40 or A20) or switching to rosuvastatin 10 mg (R10). The effect of these regimens on novel biomarkers of atherogenic dyslipidemia (low‐ and high‐density lipoprotein particle number and lipoprotein‐associated phospholipase A2 [Lp‐PLA2]) was assessed.Methods and ResultsTreatment effects on low‐ and high‐density lipoprotein particle number (by NMR) and Lp‐PLA2 (by ELISA) were evaluated using plasma samples available from 358 subjects in the study. Switching to ES10/20 reduced low‐density lipoprotein‐particle number numerically more than did statin dose‐doubling and was comparable with R10 (−133.3, −94.4, and −56.3 nmol/L, respectively; P>0.05). Increases in high‐density lipoprotein particle number were significantly greater with switches to ES10/20 versus statin dose‐doubling (1.5 and −0.5 μmol/L; P<0.05) and comparable with R10 (0.7 μmol/L; P>0.05). Percentages of patients attaining low‐density lipoprotein particle number levels <990 nmol/L were 62.4% for ES10/20, 54.1% for statin dose‐doubling, and 57.0% for R10. Switching to ES10/20 reduced Lp‐PLA2 activity significantly more than did statin dose‐doubling (−28.0 versus −3.8 nmol/min per mL, P<0.05) and was comparable with R10 (−28.0 versus −18.6 nmol/min per mL; P>0.05); effects on Lp‐PLA2 concentration were modest.ConclusionsIn diabetic patients with dyslipidemia, switching from statins to combination ES10/20 therapy generally improved lipoprotein subclass profile and Lp‐PLA2 activity more than did statin dose‐doubling and was comparable with R10, consistent with its lipid effects.Clinical Trial RegistrationURL: http://www.clinicaltrials.gov. Unique identifier: NCT00862251.

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Section: Introductionmentioning

confidence: 99%

Effect of Switching From Statin Monotherapy to Ezetimibe/Simvastatin Combination Therapy Compared With Other Intensified Lipid‐Lowering Strategies on Lipoprotein Subclasses in Diabetic Patients With Symptomatic Cardiovascular Disease

Tomassini

Tershakovec

et al. 2015

JAHA

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“…Fibrates improve all three components of the atherogenic dyslipidaemia associated with type 2 diabetes, substantially reducing triglycerides (by up to 50%) and LDL‐C, and raising HDL‐C concentrations, typically by 5–15% [28,29]. The fibrates also reduce the preponderance of small, dense LDL by promoting a shift to larger more buoyant particles (+0.32 nm) [29–31], which are less susceptible to oxidation and possess higher binding affinity for removal by the non‐atherogenic LDL receptor pathway [29]. In addition, fibrates have pleiotropic effects on the artery wall, influencing endothelial function and inflammation, as well as the coagulation and fibrinolytic systems [29].…”

Section: A Role For Fibratesmentioning

confidence: 99%

Interpreting clinical trials of diabetic dyslipidaemia: new insights

Wierzbicki

2009

Diabetes Obesity Metabolism

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Current treatment guidelines highlight the importance of aggressive lipid-modifying therapy in reducing cardiovascular risk in patients with type 2 diabetes. Statins are established as the cornerstone of dyslipidaemia management in diabetic patients, based on their efficacy in lowering levels of low-density lipoprotein cholesterol (LDL-C). However, statins fail to address the high residual cardiovascular risk in treated patients, some of which may be attributable to low HDL cholesterol (HDL-C) and elevated triglycerides and to a preponderance of small, dense LDL particles, indicating the need for further intervention. Fibrates are effective against all components of atherogenic dyslipidaemia associated with type 2 diabetes. Clinical studies, most notably the Fenofibrate Intervention and Event Lowering in Diabetes, indicate that fibrates, most likely in combination with a statin, have a secondary role in reducing cardiovascular risk in patients with type 2 diabetes, particularly in those without prior cardiovascular disease or patients with low HDL-C. Results are awaited from the ongoing Action to Control Cardiovascular Risk in Diabetes trial to fully evaluate the outcome benefits of this combination strategy.

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“…Fibrates modify the subgroup pattern of LDL-C from small, dense particles to large, buoyant particles; this effect is more pronounced with fenofibrate, involving up to 50% reduction in dense LDL-C particles levels (Shepherd et al 1985; Schonfeld 1994; Auwerx et al 1996; Guerin et al 1996; Anber et al 1997; Ruotolo et al 1998; Staels, Dallongeville, et al 1998; Feher et al 1999). Dense LDL-C particles are of elevated atherogenic potential (de Graaf et al 1991; Tribble et al 1992; Chait et al 1993; Griffin et al 1994; Anber et al 1996; Lamarche et al 1997).…”

Section: Lipid-modulating Actions Of Fenofibratementioning

confidence: 99%

Fenofibrate: a novel formulation (Triglide?) in the treatment of lipid disorders: a review

Τζιόμαλος¹,

Athyros²

2006

International Journal of Nanomedicine

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Cardiovascular disease is the major cause of mortality worldwide and accounts for approximately 40% of all deaths. Dyslipidemia is one of the primary causes of atherosclerosis and effective interventions to correct dyslipidemia should form an integral component of any strategy aimed at preventing cardiovascular disease. Fibrates have played a major role in the treatment of hyperlipidemia for more than two decades. Fenofibrate is one of the most commonly used fibrates worldwide. Since fenofibrate was first introduced in clinical practice, a major drawback has been its low bioavailability when taken under fasting conditions. Insoluble Drug Delivery-Microparticle fenofibrate is a new formulation that has an equivalent extent of absorption under fed or fasting conditions. In this review, we will discuss the clinical pharmacology of fenofibrate, with particular emphasis on this novel formulation, as well as its lipid-modulating and pleiotropic actions. We will also analyze the major trial that evaluated fibrates for primary and secondary prevention of cardiovascular disease, the safety and efficacy profile of fibrate–statin combination treatment, and the current recommendations regarding the use of fibrates in clinical practice.

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Atherogenic lipoprotein phenotype in Type 2 diabetes: reversal with micronised fenofibrate

Cited by 64 publications

References 29 publications

Effect of Switching From Statin Monotherapy to Ezetimibe/Simvastatin Combination Therapy Compared With Other Intensified Lipid‐Lowering Strategies on Lipoprotein Subclasses in Diabetic Patients With Symptomatic Cardiovascular Disease

Effect of Switching From Statin Monotherapy to Ezetimibe/Simvastatin Combination Therapy Compared With Other Intensified Lipid‐Lowering Strategies on Lipoprotein Subclasses in Diabetic Patients With Symptomatic Cardiovascular Disease

Interpreting clinical trials of diabetic dyslipidaemia: new insights

Fenofibrate: a novel formulation (Triglide?) in the treatment of lipid disorders: a review

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