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RE:A PCSK9 MEETS CV GOALS-A FIRST?

[toinv261]

Hi Jkj. Great post. What an absolutely great article. 

So if I understand it (and I am not a scientist) PCSK9 is proven to reduce LDL significantly. The issue
Was does it reduce MACE?

So now they are announcing that Amgen's drug evolocumab (Repatha) had met it's primary 
end points (3 pt MACE reduction and 5 Pt MACE reduction). 

They also state there is no concensus that the drug would be good for primary prevention in people 
without CVD and there may be (unproven) neurocognitive negative impacts.

But what I find really interesting is the expert opinion section starting on page 4 and, in particular, the 
perspective of Sek Kathiresan. 

So on page 3 they refer to FOURIER Basics - 27,000 patients with CVD, taking statins and randomized to
receive evolocumab or placebo. Trial ran until 1630 patients had a 3 pt MACE (CVD death, MI or stroke).
 
The trial is (statistically) powered at 90% to detect at least 15% relative risk reduction (RRR) for
5 point MACE if I understand it correctly.
 
So back to Sek he/she states;

1. The predicted end point for a primary MACE event was 4.5% in the control group.
2. In the test group the event rate would have to be 3.5% in order to achieve a 22% relative risk reduction.
3. So the absolute risk reduction would be 1% point (4.5% - 3.5%). (1/4.5 = 22% RRR)
4. The massive sample size seems needed in order to insure statistical significance.

 
But the absolute improvement, while better than nothing seems to be barking up the wrong tree.
 
These numbers are very different than the rvx-208 post hocs within their specific sub populations.
The RRR of 5 point MACE in the sub population of patients with diabetes mellitus, cardiovascular disease
and low HDL was 77% and the absolute risk reduction was 15% points (21% Mace in control and 6 points
in those treated with apabetalone).
 
So bottom line for me is that the multi faceted actions of apabetalone are profound. Productive
increases in functional ApoA-I seem to be a very positive path and so far the safety profile is excellent.
 
GLTA
Toinv