Amarin Corp Plc (AMRN)

[AVII77]

OK Steve, Let’s recap.

You interjected into a conversation where a Doctor incorrectly interpreted Cochrane data regarding statins in the primary prevention setting.

You acknowledged you were wrong and I was right in the interpretation of that data.

That same doctor called for a replication of the R-IT Trial.

I noted that R-IT results are a replication of JELIS and I further used the Total event analysis from the R-IT Trial to compare to his NNT in the Primary Prevention setting (corrected by me from his NNT of 18 to the correct NNT of 55 – using his data source).

You then take issue with me comparing 5 pt MACE Total event data to 3 point MACE first event data

Your criticism there has merit; I was sloppy. Score one for Steve. The point I was trying to make dealt with the replication aspect: To demand replication of an intervention that has a NNT of 6 (yes, on 5 pt Total event MACE) while at the same time being ignorant of the existence of JELIS would be arguably unethical (Of course with the caveat that you are wrong on the MO issue).

But let’s move to the main issue under debate where you assert that:

“ In a similar population, the ARR and NNT of statins outshines Vascepa”

and

“And importantly, for secondary prevention and high-risk patients, the ARR for statin adherence is far better than in REDUCE-IT.”

To argue your “Outshines” and “Far better” you compared 10 year ASCVD data to R-IT. You completely ignored (twice) the different populations.
First you compared the ASCVD (secondary prevention) data against R-IT (combined primary and secondary).

“The NNT over 10 years for ASCVD patients is “9,” and importantly, the ARR is 11% (only 3.6% in REDUCE-IT)”

That 3.6% you used comes from the combined population of R-IT in 3 pt MACE (secondary EP).

You should have used the 3 pt MACE from the secondary prevention cohort. That ARR number is 4.4% over 5 years.

I suspect you realized that a 5 yr 4.4% isn’t “far better” nor does it “outshine” a 10 year 11%.

The second time you did this you said:

“However, I cited the 3.6% ARR for a reason, as that was the ARR for Vascepa group in the key secondary endpoint of the study (hard MACE). I did that because my example also used hard MACE in its 11% ARR derivation for ASCVD risk in secondary prevention patients”

There again you compare ASCVD risk (secondary prevention) with R-IT combined populations.

Again, I suspect you realized this slight of hand and that’s why you (without acknowledging your errors) moved to the “4H” Trial.

You had me scratching my head on that one. Then I realized you meant the 4S Trial.

Now, I could argue you picked an outlier (you did) but let’s do an “apples to apples” comparison anyway.

Let’s look at 5 point MACE in this secondary prevention trial. Yes, they reported that for 4S.

The ARR was an impressive 6.7%.

Compare that to R-Its 6.2% (5 pt MACE secondary prevention)

Are you going to argue that 6.7% is “far better” or “outshines” 6.2% ? I hope not.

If you try to compare them please remember 4S was over 5.4 years and R-IT 4.9 years.

The ARR numbers are basically identical.

So there's an "apples to apples" comparison in a trial of your choice.

So, now that we have dispensed with the “far better” and “outshine” stuff let’s move on to that Forest plot you are so anxious to share showing a 4.3 fold increase in the risk of death in patients who discontinued clopidogrel in the CHARISMA Trial.

Let’s make three things clear (you probably know this but just for the benefit of anyone following along):

First, CHARISMA wasn’t a statin trial.

Second, that 4.3 fold increase in death was for those who discontinued clopidogrel and for those who discontinued Placebo.

Third; CHARISMA failed to demonstrate a benefit in clopidogrel plus aspirin over aspirin (HR=0.93 w/p= .22).

You use this data to make a case that MO interfering with statins (and other meds) is essentially the same as a patient discontinuing treatment and point to the increased risk of death as an outcome.

This is silly Steve.

If you read and understood the papers that this Forest plot came from you would see that the authors show it wasn’t the discontinuation of the drug that caused their death. It was that the patients who discontinued treatment represented a subgroup with a higher risk of death.

The discontinuation wasn’t “casual” of an increased risk of death , it was “correlated” with an increased risk of death.

Or, as the authors note:

“Such data implicate a potential ‘healthy adherer’ or ‘sick stopper’ effect where confounding factors may drive outcomes independently of drug.”

Or, as others note: “patients who take their medication as prescribed are more likely to engage in a broad spectrum of health-promoting behaviors that lower the risk of mortality.”

I'm pretty sure that's an argument you used to predict R-IT would fail (people who eat a lot of fish live a healthier lifestyle)

I know you are trying to get people to believe that MO blocking medication is the same as non-adherence (and that increased death is a consequence). This Forest plot certainly doesn't come close to demonstrating that.

Hope the new family is well. I'm taking the Hobie out next weekend as another season at the lake comes to a close.