Prescribing Advice for GPs

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A spotlight on the ILLUSTRATE Trial

The New England Journal of Medicine has published the results of the ILLUSTRATE Trial1. The full article is currently available through early release.

This trial aimed to assess the impact of torceptrapib, a drug that increases level of high-density lipoprotein cholesterol (HDL-C), on progression of atherosclerosis. All development work on torceptrapib was stopped late last year after an increased number of deaths were recorded in patients taking this drug, possibly as a consequence of increases in blood pressure.

The study recruited 1,188 patients and treated low-density lipoprotein cholesterol (LDL-C) to below 2.59mmol/L using atorvastatin. Patients were then randomised to torceptrapib or placebo.

Despite the torceptrapib arm significantly increasing the level of HDL-C (by 61% relatively speaking) there was no difference in progression of atherosclerosis with a 0.12% increase in the active arm and a 0.19% increase in the placebo arm. This study also noted increases in blood pressure with a mean difference in systolic blood pressure of 4.5mmHg. There were also more cardiovascular events noted in the active arm of the study although these were not statistically significant and the study was not powered to detect these differences.

According to PharmaTimes, the manufacturer of atorvastatin is "putting a positive spin" on these results by highlighting that atorvastatin treatment alone (in the placebo arm) halted progression of atherosclerosis. This assertion would of course require further investigation since the original study was not designed to assess this outcome. Additionally, it remains unclear if halting or reversing atherosclerosis directly delivers reductions in fatal and non-fatal cardiovascular events.

Action: Simvastatin 40mg remains the statin of choice for lipid lowering therapy as required in the prevention of cardiovascular events.

  1. ILLUSTRATE is the Investigation of Lipid Level Management Using Coronary Ultrasound to Assess Reduction of Atherosclerosis by CETP Inhibition and HDL Elevation

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2 Comments to “A spotlight on the ILLUSTRATE Trial”

  1. [...] levels of HDL are known to be associated with IHD but it is unclear if the relationship is causal. Recent attempts to produce drugs that increase levels HDL and therefore reduce cardiovascular morbidity and [...]

    Pingback by Prescribing Advice For GPs » IHD And HDL Relationship Queried — June 5, 2008 #
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  2. […] levels of HDL are known to be associated with IHD but it is unclear if the relationship is causal. Recent attempts to produce drugs that increase levels HDL and therefore reduce cardiovascular morbidity and […]

    Pingback by IHD And HDL Relationship Queried | Prescribing Advice For GPs — June 5, 2008 #
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