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.
- ILLUSTRATE is the Investigation of Lipid Level Management Using Coronary Ultrasound to Assess Reduction of Atherosclerosis by CETP Inhibition and HDL Elevation
The two manufacturers of donepezil are taking the National Institute for Health and Clinical Excellence (NICE) to court after the recently published and controversial guidance on Alzheimer's drugs according to the BBC.
This particular guidance is a Technology Appraisal, NICE detail on their website that the process involves consideration of two factors:
- Clinical evidence - measuring how well the medicine or treatment works
- Economic evidence - measuring how well the medicine or treatment works in relation to how much it costs the NHS - does it represent value for money?
This judicial review may reveal more details of the calculations used by NICE to derive an indication of efficacy and value for money however the full guidance reveals the full detail the process with examination and interpretation of the evidence covering some 40 pages!
This action has the unfortunate consequence of diverting resources including staff time and money away from generating guidance for the benefit of the NHS. A speedy resolution would be of greatest benefit to the NHS.
Action: Clinicians who prescribe treatments for Alzheimer's disease should continue to implement the current guidance until the outcome of this review is completed.