RE:RE:RE:RE:RE:RE:RE:RE:RE:INTERESTING ARTICLE RE cholesterol EFFLUX AS MEASURE OF HDL I'm probably way off base but there is something that struck me about this (Prof Norman Miller's POV - which makes sense to me). It suggests to me that there is a gap in the understanding of the various biochemical pathways in terms of why rvx-208 can achieve a relative risk reduction RRR in MACE events of 77% (i.e.I see this (RRR MACE) as an
end point measure as opposed to an interim measure such as an increase in HDL (who knows what else could have been measured and wasn't in the research to complete the equation) and if MACE was reduced, no matter how it happened, as long as it was safe, then good for rvx-208!!!).
(Note, I recognize that the RRR relates to a subset of patients in the combined ASSURE/SUSTAIN trial... those with DM and CVD.)
For example based on the ASSURE trial of 281 patients in the results we saw
- Multiple secondary IVUS endpoints such as Total Atheroma Volume (TAV) and 10mm worst occluded TAV were met with high statistical significance with p<0.001 and p<0.001, respectively.
- Additional secondary lipid biomarker endpoints such as HDL and ApoA-I were also met 10.73% p<0.001, 11.69% p<0.001, respectively.
And yet the primary endpoint in ASSURE, -0.6% change in PAV (adjusted percent atheroma volume) was not met. The RVX-208 treated group had -0.4% median plaque regression (p=0.08). (I recognize the mistakes made by CC but let's just leave them in as noise in the data).
So here is my hypothetical (and somewhat pointless question given Dr Miller's POV) question regarding rvx-208 in relation plaque regression.
- Suppose that the ASSURE sample size would have been large enough such that the PAV regression of -.04% in this 26 week trial was statistically significant at the p<.001 level i.e. rvx-208's plaque regression performance was probably not a random event and therefore there probably was a real, positive impact.
- My question to the science posters is would a PAV regression of -0.4% every 6 months be considered a functionally significant benefit from a medical point of view and would this level of regression be of value to patients (particularly if untreated, their plaques levels continued to grow)?
Anyway, no need to worry, MACE is now the endpoint.
Cheers
Toinv :) I shall rant and ramble into the bliss!