Financiado en parte por Eli Lilly and Company, AstraZeneca, Pfizer Canada, Pfizer Pharmaceuticals
Cholesteryl ester transfer protein inhibition, high-density lipoprotein raising, and progression of coronary atherosclerosis: insights from ILLUSTRATE (Investigation of Lipid Level Management Using Coronary Ultrasound to Assess Reduction of Atherosclerosis by CETP Inhibition and HDL Elevation)
Nicholls SJ, Tuzcu EM, Brennan DM, Tardif JC, Nissen SE
Circulation · 156 citas
Etiquetas de revisión
Financiado por la industriaDatos neutrales que nuestra revisión registró sobre cómo se hizo este estudio. Describen el método, nunca si nos gusta el resultado.
Cómo se estudió
- Diseño
- Ensayo controlado aleatorizado (indexado por PubMed)
- Estudiado en
- Personas
- Resultado principal
- Marcadores de salud y funcionamiento
Quién lo pagó
- Financiación
- Financiado por la industria
- Empresa
- Eli Lilly and Company
- Empresa
- AstraZeneca
- Universidad u hospital
- Cleveland Clinic
- Empresa
- Pfizer Canada
- Empresa
- Pfizer Pharmaceuticals
- Gobierno
- Canadian Institutes of Health Research
Según 6 financiadores declarados.
Publicación
- Publicado
- 2008-11-24 · Circulation · vol. 118 · número 24 · págs. 2506–2514
- Editorial
- Lippincott Williams & Wilkins
- Citado
- 213 citas · más que el 100% de estudios similares · 28.8× el promedio de su campo
- Impacto
- Entre el 10 % más citado de su campo
- Referencias
- 52 trabajos
- Acceso
- Lectura gratuita
- Áreas de investigación
- Lipoproteins and Cardiovascular Health · Cholesterol and Lipid Metabolism · Atherosclerosis and Cardiovascular Diseases
- Palabras clave
- cholesteryl ester transfer protein inhibition, torcetrapib, atorvastatin, coronary atherosclerosis progression, atheroma volume, HDL cholesterol, LDL cholesterol, serum sodium, serum potassium, lipid-lowering therapy, intravascular ultrasound, atherosclerosis regression, statins, mortality risk
- MeSH
- humans, disease progression, potassium, sodium, pyrroles, quinolines, heptanoic acids, lipoproteins, hdl, ultrasonography, aged, middle aged, female, male, cholesterol ester transfer proteins, coronary artery disease, atorvastatin
5 autores
- Stephen James Nicholls🇺🇸🇨🇦Cleveland Clinic; Montreal Heart Institute
- Emin Murat Tuzcu🇺🇸🇨🇦Cleveland Clinic; Montreal Heart Institute
- Danielle M. Brennan🇺🇸🇨🇦Cleveland Clinic; Montreal Heart Institute
- Jean‐Claude Tardif🇺🇸🇨🇦Cleveland Clinic; Montreal Heart Institute
- Steven E. Nissen🇺🇸🇨🇦Cleveland Clinic; Montreal Heart Institute
Resumen
El texto original del estudio, en el idioma en que se publicó.
Background
Despite favorable effects on high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol, the cholesteryl ester transfer protein inhibitor torcetrapib failed to slow atherosclerosis progression and increased mortality. We investigated the relationship between lipid changes and progression of coronary atherosclerosis.
Methods and results
Intravascular ultrasound was performed at baseline and follow-up in 910 participants randomized to torcetrapib/atorvastatin or atorvastatin monotherapy. The relationship between changes in lipoprotein levels and the primary intravascular ultrasound end point, change in percent atheroma volume, was investigated. Compared with atorvastatin monotherapy, torcetrapib raised HDL-C by 61%, lowered low-density lipoprotein cholesterol by 20%, raised serum sodium (0.44+/-0.14 mmol/L, P=0.02), and lowered serum potassium (0.11+/-0.02 mmol/L, P<0.0001). Despite substantial increases in HDL-C, no effect was found of torcetrapib on percent atheroma volume. In torcetrapib-treated patients, an inverse relationship was observed between changes in HDL-C and percentage atheroma volume (r=-0.17, P<0.001). Participants with regression had greater increases in HDL-C (mean+/-SE, 62.9+/-37.4% versus 54.0+/-39.1%, P=0.002). Compared with the lowest quartile, torcetrapib-treated patients in the highest quartile of HDL-C change showed the least progression (-0.31+/-0.27 versus 0.88+/-0.27%, P=0.001). The highest on-treatment HDL-C quartile showed significant regression of percent atheroma volume (-0.69+/-0.27%, P=0.01). In multivariable analysis, changes in HDL-C levels independently predicted the effect on atherosclerosis progression (P=0.001).
Conclusions
The majority of torcetrapib-treated patients demonstrated no regression of coronary atherosclerosis. Regression was only observed at the highest HDL-C levels. Torcetrapib raised serum sodium and lowered potassium, consistent with an aldosterone-like effect, which may explain the lack of favorable effects in the full study cohort. Accordingly, other cholesteryl ester transfer protein inhibitors, if they lack this off-target toxicity, may successfully slow atherosclerosis progression.
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