Effect of Torcetrapib on the Progression of Coronary Atherosclerosis

Nissen, Steven E.; Tardif, Jean‐Claude; Nicholls, Stephen J.; Revkin, James H.; Shear, Charles L.; Duggan, William; Rużyłło, Witold; Bachinsky, William; Lasala, Gregory P.; Tuzcu, E. Murat

doi:10.1056/nejmoa070635

Cited by 897 publications

(532 citation statements)

References 30 publications

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“…Despite their beneficial effects on these lipoprotein traits, three of four large randomized controlled outcome trials on the clinical efficacy of add-on-statin therapy with CETP inhibitors have been stopped prematurely because of excess cardiovascular and overall mortality (torcetrapib) or futility (dalcetrapib and evacetrapib). 188,189,190 Anacetrapib is the only CETP inhibitor, which is under ongoing phase 3 trial investigation for efficacy in preventing clinical endpoints. In the DEFINE (Determining the Efficacy and Tolerability of CETP Inhibition with AnacEtrapib) trial including 1623 patients with known cardiovascular heart disease or at high risk of CHD, co-administration of anacetrapib 100 mg once daily with a statin for 24 weeks provided an additional 40% reduction in LDL-cholesterol and 138% increase in HDL-cholesterol compared with the statin plus placebo group, 191 irrespective of the patient subgroup.…”

Section: Fibratesmentioning

confidence: 99%

Dysfunctional high-density lipoproteins in coronary heart disease: implications for diagnostics and therapy

Annema

Eckardstein

2016

Translational Research

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Low plasma levels of high-density lipoprotein (HDL) cholesterol are associated with increased risks of coronary heart disease. HDL mediates cholesterol efflux from macrophages for reverse transport to the liver and elicits many anti-inflammatory and anti-oxidative activities which are potentially antiatherogenic. Nevertheless, HDL has not been successfully targeted by drugs for prevention or treatment of cardiovascular diseases. One potential reason is the targeting of HDL cholesterol which does not capture the structural and functional complexity of HDL particles. Hundreds of lipid species and dozens of proteins as well as several microRNAs have been identified in HDL. This physiological heterogeneity is further increased in pathologic conditions due to additional quantitative and qualitative molecular changes of HDL components which have been associated with both loss of physiological function and gain of pathologic dysfunction. This structural and functional complexity of HDL has prevented clear assignments of molecules to the functions of normal HDL and dysfunctions of pathologic HDL. Systematic analyses of structure-function relationships of HDL-associated molecules and their modifications are needed to test the different components and functions of HDL for their relative contribution in the pathogenesis of atherosclerosis. The derived biomarkers and targets may eventually help to exploit HDL for treatment and diagnostics of cardiovascular diseases.

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Section: Fibratesmentioning

confidence: 99%

Dysfunctional high-density lipoproteins in coronary heart disease: implications for diagnostics and therapy

Annema

Eckardstein

2016

Translational Research

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“…The fi rst CETP inhibitor, torcetrapib, increased HDL-C levels by approximately 60% ( 29 ), but it failed to demonstrate any effect on the primary atherosclerotic burden as assessed by carotid intima-media thickness and coronary intravascular ultrasound imaging ( 30,31 ), and it even increased cardiovascular events and mortality, accompanied by off-target effects Fig. 9.…”

Section: E3lmentioning

confidence: 99%

CETP expression reverses the reconstituted HDL-induced increase in VLDL

Wang

Berbée

Stroes

et al. 2011

Journal of Lipid Research

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“…Similarly, the ILLUSTRATE trial, which used IVUS endpoints to compare the effects of torcetrapib/atorvastatin vs. atorvastatin alone, found no beneficial effect of torcetrapib treatment on progression of atherosclerosis, despite a significant increase in HDL levels in the torcetrapib/atorvastatin treatment group relative to the atorvastatin alone group 121 . Correlation between lumen and plaque burden As described above, the rational for plaque imaging has been the limitations of angiography.…”

Section: Correlation Between Ivus and Cimtmentioning

confidence: 99%

Métodos por imagem da aterosclerose em estudos de progressão/regressão: marcador substituto ou janela direta para o processo patológico da aterosclerose?

Schoenhagen¹,

Tuzcu²

2008

Arq. Bras. Cardiol.

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SummaryCAD remains a major global cause of morbidity and mortality. Comprehensive drug development programs of novel pharmacological treatment strategies frequently utilize traditional mortality/morbidity endpoints studies and additional surrogate endpoints trials. This parallel approach allows an assessment of efficacy several years in advance of the availability of data from clinical endpoint trials. Several atherosclerosis imaging markers have been introduced into these drug-development strategies, including angiography, carotid ultrasound, IVUS, MRI, and CT. This review will discuss the current status of atherosclerosis imaging as an endpoint in progression/regression trials, with an emphasis on evidence-based data. In addition to a discussion of the results of individual imaging modalities, the emerging data comparing different modalities and approaches are presented.

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Effect of Torcetrapib on the Progression of Coronary Atherosclerosis

Cited by 897 publications

References 30 publications

Dysfunctional high-density lipoproteins in coronary heart disease: implications for diagnostics and therapy

Dysfunctional high-density lipoproteins in coronary heart disease: implications for diagnostics and therapy

CETP expression reverses the reconstituted HDL-induced increase in VLDL

Métodos por imagem da aterosclerose em estudos de progressão/regressão: marcador substituto ou janela direta para o processo patológico da aterosclerose?

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