Comment by breadwinner

You should actually read the article. In particular:

> Fourteen trials recruited patients with specific conditions (raised lipids, diabetes, hypertension, microalbuminuria). All‐cause mortality was reduced by statins (OR 0.86, 95% CI 0.79 to 0.94); as was combined fatal and non‐fatal CVD RR 0.75 (95% CI 0.70 to 0.81), combined fatal and non‐fatal CHD events RR 0.73 (95% CI 0.67 to 0.80) and combined fatal and non‐fatal stroke (RR 0.78, 95% CI 0.68 to 0.89). Reduction of revascularisation rates (RR 0.62, 95% CI 0.54 to 0.72) was also seen.

So the evidence base is a collection of studies where most of the participants had at least one prior indicator of CVD or diabetes, and their outcome is a relatively weak benefit to all-cause mortality, CVD, CHD and stroke. For primary prevention, what you really want is a strong outcome in a study of people without any prior indication of disease [1].

I think the article posted by parent is exaggerating, but even the Cochrane review is pulling its punches here, saying specifically "cost-effective in primary prevention", instead of the stronger claim. Common jokes about putting statins in the water supply aside, there's not a ton of evidence for giving them to, say, otherwise healthy 20-somethings.

[1] Imagine the following, not-uncommon scenario: you have an otherwise healthy patient who is both pre-diabetic, as well as presenting with elevated cholesterol. Statins have a tendency to elevate blood glucose. So which risk do you choose?

The available evidence provides poor guidance.

It’s not that lowering cholesterol does not decrease heart disease, but the fundamental problem of heart disease is not cholesterol, it’s the inflammation.

Lowering cholesterol lowers the amount of oxidized cholesterol that is caused from inflammation. The fact is is that in inflammation is the fundamental disorder, not high cholesterol on its own.

And after 2013 in the BMJ on statins:

https://www.bmj.com/campaign/statins-open-data

Published 2013

It's true that most doctors and pharmaceutical companies maintain that statins are effective. But there are plenty of statistically educated people that don't think they have much of an effect on all-cause mortality.

There are conflicting incentives here, and as usual we don't care about someone else's p value, we care about argmaxing our own utility functions.

And my understanding of the science is that statins reduce inflammation.

> This is not a mainstream view of the science, and it's worth noting that this perspective is also not supported by the OP or by the JACC article that it's citing.

Your comment is an appeal to authority. While I have my problems with characterizing statins as dangerous drugs, the article is not particularly spicy. In particular, this part:

> Because the link between excessive LDL cholesterol and cardiovascular disease has been so widely accepted, the Food and Drug Administration generally has not required drug companies to prove that cholesterol medicines (such as statins) actually reduce heart attacks before approval. So drug companies have not had to track whether episodes like heart attacks are reduced.

...is true, and controversial only amongst people who don't know the evidence. Which, unfortunately, is many doctors and "experts".

In general, saying any variation on "experts disagree" is not a rebuttal to a question of medical evidence. You would perhaps be surprised to know how many practicing physicians have no idea what level of evidence backs the drugs that they prescribe.

> They're all news articles.

Correct, but if you read the news articles you'll see that they are reporting results from scientific articles and clinical trials. In other words, it is not the reporter's opinions.

Sure statins may have saved lives, but the question is how. Is it by controlling LDL, or by reducing inflammation? This story says it is the latter: https://www.bloomberg.com/news/articles/2008-04-15/heart-dis...

Most of this is reputation is based on early generation statins. The side effect profile is incredibly slimmed down on statins like rosuvastatin.

> Age-standardized cardiovascular mortality dropped steadily from 1975 to 2010 (with no particular discontinuity when statins were introduced), and has not budged since 2010.

Why would we favour cross sectional data over that produced by more rigorous methodologies?

> the tiny effect that statins claim (25-35%, under particular conditions)

25-35% reduction in one of the west’s leading killers is tiny? Wild.

I'm unaware of any evidence for ppcsk9 inhibitors outside of the same cohorts (people with existing CVD) that the OP is citing.

Do you have any?

What about Vytorin trial?

Vytorin is a combination of cholesterol-lowering drugs, one called Zetia and the other a statin called Zocor. Because the two drugs lower LDL cholesterol by different mechanisms, the makers of Vytorin (Merck and Schering-Plough) assumed that their double-barreled therapy would lower it more than either drug alone, which it did, and so do a better job of slowing the accumulation of fatty plaques in the arteries - which it did not.

See: https://www.nytimes.com/2008/01/27/opinion/27taubes.html

So you are saying the human body manufactures a substance that is extremely harmful to the body. And yet lowering it artificially can lead to issues such as loss of short term memory. The body needs cholesterol! You could qualify your argument by saying that excess LDL is harmful.

> The cholesterol to heart disease link is one of the best attested in medical science

What about this:

Cholesterol lowering is not the reason for the benefit of statins. If it was, lowering cholesterol via any means should have produced the same benefit, but it doesn’t. One obvious way to confirm this is to find therapies that lower cholesterol by different means (i.e., other than statins) and see if they, too, prevent heart attacks. They don’t. See: https://www.nytimes.com/2008/01/27/opinion/27taubes.html (Some will discredit the author Gary Taubes without addressing the points he is raising.)

The main reason why statins work may not be because they lower cholesterol, but because they reduce the inflammation that leads to heart attacks: https://www.bloomberg.com/news/articles/2008-04-15/heart-dis...

This last link aligns with the new findings.

It's a bad blog post for sure. However, I've a few smart people say that lower cholesterol may not be what makes statins powerful: it's the anti-inflammatory properties. I'm too lazy to find papers right now.