Efficacy and safety of dalcetrapib in type 2 diabetes mellitus and/or metabolic syndrome patients, at high cardiovascular disease risk

Stalenhoef, Anton F. H.; Davidson, Michael; Robinson, J; Burgess, Tracy; Duttlinger-Maddux, Regina; Kallend, David; Goldberg, Anne C.; Bays, Harold

doi:10.1111/j.1463-1326.2011.01485.x

Cited by 11 publications

(6 citation statements)

References 26 publications

(32 reference statements)

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“…This difference in cholesterol ester transfer protein activity between the two population groups is similar in extent to the cholesterol ester transfer protein activity elevation levels demonstrated in humans with the metabolic syndrome dis-playing the atherogenic dyslipoproteinemia when compared with normal healthy controls [10]. Furthermore, cholesterol ester transfer protein activity correlated strongly with all of the major elements of the atherogenic dyslipoproteinemia -high LDL particle number, elevated triglycerides and low HDL-C in both European Caucasians and South Asians [11,31]. These findings mean that the difference in cholesterol ester transfer protein activity plays a key role in the differences in the lipoprotein profiles among the populations.…”

Section: Elevated Cholesterol Ester Transfer Protein (Cetp) Activitysupporting

confidence: 65%

Critical role of cholesterol transfer protein in atherosclerosis development

Dorovsky¹,

Zagayko²

2016

Ukr. bìofarm. ž.

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Cholesterol ester transfer protein (CETP) is a plasma protein that facilitates the transport of cholesterol esters and triglicerides between the lipoproteins. CETP collects triglycerides from very-low-density lipoproteins (VLDL) or low-density lipoproteins (LDL) and exchanges them for cholesterol esters from high-density lipoproteins (HDL). Mutations wich lead to the cholesterol ester transfer protein function reduction have been involved in atherosclerosis development. This mutations also increase the prevalence of coronary heart disease in patients with hypertriglyceridemia. There is a wide variety of HDL-C increase therapies that have been tested during the last ten years. Among them is the modification of cholesterol ester transfer protein function. A novel pharmacologic strategy was proposed where drugs are designed to modify the lipid substrate preference of cholesterol ester transfer protein instead of simply blocking its activity. This approach provides an opportunity to improve the lipid transfer properties of cholesterol ester transfer protein and to harness its capacity to alter lipid metabolism to achieve specific beneficial outcomes.

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Section: Elevated Cholesterol Ester Transfer Protein (Cetp) Activitysupporting

confidence: 65%

Critical role of cholesterol transfer protein in atherosclerosis development

Dorovsky¹,

Zagayko²

2016

Ukr. bìofarm. ž.

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“…114 A lack of benefit of niacin/laropiprant added to statin therapy has also been reported recently for the large Heart Protection Study 2 Treatment of HDL to Reduce the Incidence of Vascular Events (HPS2-THRIVE) study. 115,116 Cholesteryl ester transfer protein (CETP) inhibitors provide more robust elevations in HDL-C, 117 and studies are ongoing evaluating their effects on CV outcomes. Although the dal-OUTCOMES Phase III trial, 118 which was conducted in patients with recent ACS, did not demonstrate clinically meaningful efficacy for dalcetrapib, leading to the cessation of the dal-HEART program, 119 it cannot be used to draw any definitive conclusions about the effect of raising HDL-C levels on CV outcomes.…”

Section: Dyslipidaemia Managementmentioning

confidence: 99%

The clinical burden of type 2 diabetes in patients with acute coronary syndromes: Prognosis and implications for short- and long-term management

Katz

Leiter

Mellbin

et al. 2014

Diabetes and Vascular Disease Research

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Type 2 diabetes mellitus (T2DM) is associated with increased morbidity and mortality in patients with acute coronary syndromes (ACS). Cardiometabolic risk factors, including hyperglycaemia, insulin resistance, atherogenic dyslipidaemia, increased visceral fat and inflammation, are associated with increased risk in this population and represent potential targets for treatment. In this review, management strategies for patients with T2DM post-ACS, both in the acute-care setting and in the long-term, are discussed. Although the benefits of long-term, aggressive, multifactorial risk factor modification are well established, a significant burden of recurrent events remains and the search for novel strategies continues. Several studies are assessing the potential cardiovascular (CV) benefits and safety of various classes of newer agents. Of these, AleCardio (aleglitazar), Examination of Cardiovascular Outcomes With Alogliptin versus Standard of Care in Patients With Type 2 Diabetes Mellitus and Acute Coronary Syndrome (EXAMINE; alogliptin) and Evaluation of LIXisenatide in Acute Coronary Syndrome (ELIXA; lixisenatide) specifically address patients with type 2 diabetes post-ACS. The mechanisms of action of these new therapies and aims of the CV outcome studies are briefly reviewed. The prevalence of type 2 diabetes continues to increase worldwide highlighting the need for new strategies that address the complex underlying processes that drive atherosclerosis and CV events in this high-risk patient population.

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“…However, no effects on fasting glucose or HbA1c levels were found in the DAL-outcomes study, a larger study and of longer duration than ILLUMINATE, and where new-onset diabetes rates were similar between those who were taking CETP inhibitors and those who were only taking the statin. 19,22 Therefore, it still remains unclear whether CETP inhibition may be a promising intervention for modulation of glucose homeostasis, either for full therapeutic use in patients with diabetes or as an additional benefit should this drug category manage to get FDA approval for dyslipidemia.…”

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confidence: 99%