RE:DO BLOOD LEVELS OF APOA-1 REALLY MATTER SO MUCH????SanFran,
I can't seem to access the RVX webcast that split up the ASSURE results by lipitor vs. crestor. However, I recall that, similar to the reduction in MACE, reduction in plaque volume, and increase in HDL-C, that the group that received RVX-208 AND crestor showed significant increase in apoAI as well. Here is a quote from the 9/3/13 news release (I can't access the webcast though):
"The responder population (i.e. HDL <39 mg/dL taking Rosuvastatin and RVX-208) exceeded the primary endpoint and also surpassed secondary endpoints reflecting regression in coronary atherosclerosis. These measures included total atheroma volume (TAV) and changes in the 10 mm most diseased segment of the coronary arteries, we noted marked regression versus baseline of -12.3 mm3 ( p< 0.0001) and -4.3 mm3 (p<0.0001), respectively. Other secondary endpoints assessed in this population were biomarkers of reverse cholesterol transport (RCT), including: HDLc, ApoA-I and large HDL particles which increased by 18.2% (p<0.0001), 16.4% (p<0.0001) and 74.7% (p<0.0001), respectively, vs. baseline."
If the Seeking Alpha article author was strictly looking at the pooled data (lipitor and crestor combined), then I agree that one might not be too impressed. But keep in mind that it wasn't until the post-hoc analysis of ASSURE that the RVX team begain to appreciate the synergistic value of crestor plus RVX-208. ASSERT, SUSTAIN, ASSURE all contained many many patients also taking statins if I remember correctly, so those taking lipitor may have been confounding the data.
Though yet to be solidly proven, there have been some data suggesting that lipitor somewhat inhibits the ABCA1 pathway, while crestor enhances the ABCA1 pathway. ABCA1 is essential for the early lipidation steps of apoAI maturation. ApoAI is the necessary apolipoprotein component of HDL. ApoAI doesn't really "transform" into something else. A better way of stating it is that the apoAI-containing lipoprotein particle matures into a more stable HDL molecule.
Also, keep in mind that crestor itself has been shown to significantly elevate plasma HDL (and possibley apoAI), possibly due to this ABCA1-enhancement. So one needs to be clear what question they are asking: 1) does RVX-208 by itself (no crestor) raise apoAI/HDL compared to those not taking RVX-208 or crestor, 2) does RVX-208 IN ADDITION to crestor raise apoAI/HDL relative to those taking crestor alone, or 3) does RVX-208 when combined with crestor raise apoAI/HDL more than the placebo group.
Personally, I think that seeking alpha statement on the lack of effect on apoAI was unfair and did not take into account the latest post-hoc analysis finding.
BDAZ