#2565

for all-cause mortality, the RD (absolute risk difference) was less than 1% (OR 0.43, 95% CI 0.14 to 1.30; 3 studies, 5223 participants; very low-certainty evidence)

PCSK9 monoclonal antibodies for the primary and secondary prevention of cardiovascular disease - PubMed (nih.gov)

#2568

I donā€™t know, if youā€™re paying money to die more that seems kinda dumb.

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#2571

Donā€™t you think that you donā€™t need a degree in statistics to realize that if drug is effective for the intended disease but not for ACM, that the treatment is causing harm on another level. You might say it is statically insignificant but it is far cry from proof you are saying is there.

#2573

@scta123 and @L_H

Iā€™m with @AnUser on this one 100%

All cause mortality is just such a statically noisy concept - youā€™d need massively larger (and/or massively longer) trials if you wanted to pick up a signal on that with statical confidence.
(Edit, for clarity, to pick up the signal from the drug (in this case PCSK9i) driving all cause mortality (which is different from and much harder than picking up a signal on whether all cause mortality was just different in the groups)

This is a bit unintuitive, but if you skim the paper @AnUser linked above for just 5-10 min I think it will help you evaluate (and then see and believe) why what we are saying here is correct.

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#2575

I am all pro philosophy but statistics can be used in my opinion as ā€œsmoke and mirrorsā€. That is my personal opinion based on clinical research I was involved with a while ago and when raw data was analyzed the team was directly asked by the data analyst what kind of results do we want and showed us with few clicks on the keyboard how curves can change without any falsifying of data. It is great that you believe in statistics but having an open mind when interests behind some of these studies are measured in billions of yearly revenue must be taken into account. I donā€™t think that lipid lowering drugs are worthless or even causing harm intentionally, but the proof that you are saying is there I canā€™t justify with these studies. And you have to trust the ethics of researchers that have interests and biases to begin with. Lipid lowering is great for high risk patients and secondary prevention but as a primary prevention of low risk individuals there are still some open questions that I am concerned with but you seem not and this is just fine. I just believe that your ā€œpropagandaā€ is just that, biased view and donā€™t get me wrong we are all biased and maybe I am biased towards my mistrust to Pharma industry but truth is not black and white but usually a mosaic of shades of gray.

I also want to point out that my mistrust is sometimes widely exaggerated just to counter sometimes blind belief in certain interventions and sometimes just to open a broader debate on some interventions. I am very curious by nature and having more views sometimes just promotes my own curiosity and research.

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#2577

Finally, there is very limited evidence on any potential safety issues of both evolocumab and alirocumab. While the current evidence synthesis does not reveal any adverse signals, neither does it provide evidence against such signals. This suggests careful consideration of alternative lipid lowering treatments before prescribing PCSK9 inhibitors.

https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD011748.pub3/full#CD011748-sec-0067

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#2579

I recall a book from my youthā€¦something like, lies, damned lies, and statistics. Itā€™s right to keep an open mind but not so open your brain falls out (to steal another quote).

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#2580

Yes, Iā€™m not saying its statistically significant. But it is noteworthy. There is obviously more noise around all cause mortality. But given the high percentage of cvd deaths in a population with pre-existing cvd, and given the size of this studyā€¦ Itā€™s a shame they terminated it early at 2.2 years, a few months after the all cause mortality signal started emerging. If it had been allowed to run for the full period, itā€™s likely that the study would have been sufficiently powered for all call cause mortality.

The fact that the research groupā€™s judgement on what constituted a cvd death differed from the local clinicians in 41% of the deaths. And the fact that the reviewing researchers disagreed after reviewing the same clinical dataā€¦ Makes me highly dubious that we should rely on cvd death classifications.

But my main disinclination to target the ldlc levels suggested by the fourier trial remains that it is inapplicable to me because it recruited only subjects with pre-existing cvd. And having only a 2.2 year follow up, that doesnā€™t give much comfort as to the long term safety and efficacy of targeting super low ldlc.

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#2581

It wouldnā€™t need to be massively longer or bigger, because the subjects in the fourier trial all had pre-existing cvd. So CvD deaths make up a big proportion of all deaths.
The trial was terminated early on slightly dubious grounds just as the signal was emerging.

#2583

For what?

(Extra characters)

#2584

Itā€™s all very confusing. My cardiologist recommends that I start Repatha, and now I donā€™t know what to do.

#2586

We used to have a book in our works library entitled ā€œHow to lie with Statistics"ā€¦.and this was a major pharmaceutical company !

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#2589

I understand your sarcasm, but Iā€™m seeking a real advice or at least a friendly opinion. Repatha does have side effects and some are pretty concerning. And I had some serious allergic reactions on new medications in the past, including two anaphylactic shocks. Repatha also contributes to diabetes development, which I have to avoid due to transplanted kidney.

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#2590

Not sure why youā€™re asking here instead of your cardiologist and transplant doctor.

#2591

Itā€™s easier than you may realize to fall for false information nowadays. One cannot be a specialist in all areas and thereā€™s too much information to process every day. Even an AI offers false information :grinning:

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#2592

Not sure? Iā€™m seeking many opinions instead of relying just on two. Sounds logical to me. Especially, cardiologists donā€™t usually collaborate with nephrologists and vice versa. Insurance as you may guess doesnā€™t provide for such collaboration.

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#2593

I donā€™t think it hurst to have more than one opinion before taking the plunge on a new therapy/drug. Iā€™ve found that in these boars there are e few who are very knowledgeable with regards to certain drugs and conditions. I think she is right to be extra careful.

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#2594

If you are adding opinions from people not educated in medicine or research, you are just adding noise. The only few people you might consider on the forum is people like MAC or Olafarpallā€¦
P-value is a very basic error. I learned this 10 years ago.

Every single time my belief in the clinical guidelines strengthen & for mainstream medicine the more I research a problem.

I will delete these posts when forum software allows as Iā€™m tired of discussing the same things over and over with sophists who donā€™t learn. Itā€™s a bad habit anyway.

#2595

Not medical advise, but I can mention that the only prescription based medication that I personally currently am on is Repatha. I have an Lp(a) of 70 (as scale), but otherwise not cardiovascular risks.

If the repatha alone does not get me down enough (I did not when I took half the dose, but am now doing the normal 2 x 140 a month and will see), then Iā€™ll likely add Eze for a combination therapy (did get a prescription from my cardiologist for thar also).

I cannot talk to allergic reaction risks in someone prone to such things.

I partially chose Repatha because I thought it would have less impact on my blood glucose than statins (which so far seems to have been correct with HbA1cā€™s of 4.8 and 4.9 the last times).

Each of the following have supported PCSK9i as the perhaps best cholesterol option and all three care about longevity: Tom Dayspring, Peter Attia, Peter Diamandis - you could probably google and see what their current thinking is just to make sure it has not changed for some reason (but I have not seen that and so keep an eye out for it).

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#2596

Thank you. Itā€™s a great experience sharing. So you donā€™t see any detrimental effects on your glucose?