Statins and All-Cause Mortality in High-Risk Primary Prevention A Meta-analysis of 11 Randomized Controlled Trials Involving 65 229 Participants

“In conclusion, based on aggregate data on 65 229 men and women from 11 studies, yielding approximately 244 000 person-years of follow-up and 2793 deaths, we observed that statin therapy for an average period of 3.7 years had no benefit on all-cause mortality in a high-risk primary prevention population. Current prevention guidelines endorse statin therapy for subjects at high global risk of incident CVD as a means to reduce fatal and non fatal vascular events.33,35,36 Due consideration is needed in applying statin therapy in lower-risk primary prevention populations”

Point of Contact;

Kausik K. Ray, MD, MPhil, FACC, FESC, Department of Public Health and Primary Care, Strangeways Research Laboratory, Worts Causeway, Cambridge CB1 8RN, England (
other email address;

Phone number;

+44 (0)20 7594 0716

This was originally published in

Archives of Internal Medicine

Published by American Medical Association (AMA)


Lol. Doesn’t mean anything.


It means statins don’t even work on high risk primary prevention population. Much less that we should pour them in the water tower and extend everybody’s life.


Statin? This is going to be a long thread.


Why can we all just accept that whether you want to take a statin (or anything else for that matter) or not, is up to the individual.

Why do people, try to get others, to change their opinions ?


The quoted study actually shows a 9% reduction in all-cause mortality, but claim it was not statistically significant. This seems surprising given the large amount of data involved (244,000 person years) and just means that it is really hard to get enough data to validate the benefit of statins for primary prevention since the mortality rate without statin is not that high to start with, if there is no history of CVD. But that does not mean the benefit does not exist.

Consider that the unknown small subset of this study group that subsequently develop CVD is likely benefiting at least as much as in those studies that only include subjects that already have a history of CVD. As long as there is no significant downside risk for the remaining members of the study group (this study says there is only a 2.5% chance of a 1% increase in mortality) it seems logical to me to hedge my bets as to which group I belong to and just take statin anyway.


People are entitled to their opinions. However if we are addressing this factually, then opinions aren’t really relevant. As to whether someone takes statins or not is multifactorial, and I don’t care either way, but understanding the facts, and then having one’s choice whether to take them or not is where opinions come in.
Some reasonable things to consider when thinking about this meta-analysis:

  1. CAD develops over decades
  2. Events will continue to occur in individuals well after medication has started due to pre-existing disease that will take potentially 7-10 years to stabilize, or start to reverse even with ideal measures of APO B met

In the studies were the patients even optimized? Was the duration of therapy and observation a meaningful interval?

I could go on with why this “study” is meaningless, but is used be individuals who don’t understand the pathogenesis and natural course of vascular disease to think it is meaningful.

Run a study for 25 years, exclude the first 5 years of outcomes to probably significantly represent pre-existing disease, and let 50% have at it -hoot it up, let their APO B do whatever, and have the other 50% optimized to an APO B of 80 or less (if Lp(a) abnl then 50 or less) … Then we have a meaningful study to make conclusions on.

We have solid data on statins, and we don’t have the study as stated above currently - but to claim this complete rubbish of a meta analysis proves anything (and by rubbish I don’t mean it was done poorly - I just mean it is of zero scientific value) is scientific illiteracy.

Just my 2 cents on this. We should likely end this thread at this point as it is a silly waste of time.


The PI who authored the paper is more than qualified.

Just because his views are not “standard” does not mean he is not correct. In my view he is correct.

We should invite him to joined the conversation.

Part of his CV

“Professor Ray received his medical education (MB ChB, 1991) at the University of Birmingham Medical School, his MD (2004) at the University of Sheffield, a postdoctoral fellowship at Harvard Medical School and finally an MPhil in epidemiology (2007) from the University of Cambridge.
A Fellow of the American College of Cardiology, the European Society of Cardiology, the American Heart Association and the Royal College of Physicians, Kausik Ray is also a member of the British Cardiovascular Society and President-Elect of the European Atherosclerosis Society, also serving on the EAS Consensus panel and EAS Executive Committee. Professor Ray has either been the National Lead Investigator, Principal Investigator, or served on committees for several major medical trials, as well as international registries and is currently involved in 8 ongoing trials in lipids and diabetes and the PI for ORION 1, 3, 11 assessing PCSK9 inhibition through RNA interference and BETONMACE assessing BET protein inhibition in patients with ACS.”

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It matters because I am forced to pay for other people’s statin use here in the Netherlands. Fortunately very few people here seem to use them (I always do a general anamnesis of all my patients, including all medication)

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Hi Joseph, appreciate the post, but it misses the point. The meta-analysis was done correctly, and it shows short term treatment with statins in this group cannot be demonstrated to have a statistically significantly difference in outcome. I, and most specialists like me, already know this.

The problem is healthcare consumers mistake the results as indicating that statins make no difference.

Back to my original post on this - the author would agree with everything I stated.



I sent Professor Kausik, an email{today Sunday, 07 of January 2024] an invitation to join this conversation .

I am hopeful he will accept and reply.

His current contact information;

Maybe a forum member who lives in the UK can follow up with a phone call. His office phone number is posted.


If you take a look at the article, it is dispassionate science, as all such items should be. A good representation of the facts. Thinking that this physician feels there is not strong evidence for benefits for statins on vascular disease is a false conclusion.
My father, also a fellow of the American college of cardiology and professor of Cardiology at Loma Linda University has over 300 publications in the peer reviewed literature. Not all of them are things that are main stream finds convenient - but the data speaks for itself.
The contextualization and understanding of what the information means is key. That is what my original post attempted to provide. It requires medical knowledge to understand what the practical meaning is.
This study demonstrates exactly what I’d expect it to. Now get data for longer, and actually have patients optimized on their APOB, with or without drugs, and there will be a massive difference in outcomes. We have data to support that.
So this article is in no way contradictory to our understanding - it simply points out, that in the short term, don’t expect optimization of lipids to suddenly change outcomes. It is a long game both with developing vascular disease and then to stabilize or partially reverse it.
This study is completely consistent with expectations, and is useful for advising patients to not think that optimization of their lipids is suddenly going to diminish risk of events.


Nope, it does not mean that.


Conspiracy beliefs regarding cholesterol will become the greatest filter in the quest for longevity. Maybe its for the best…


I think that will turn out to be the jab.

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No, no, no! :rofl: This is just too much fun and the new life extension news is quite scarce right now, mainly about new start-ups and researchers trying to get on the bandwagon and cash in.
What I do is just ignore topics that I am tired of or not interested in.


I think the vast majority of doctors would disagree with you if you are saying statins are not beneficial and reduce CVD risk and all-cause mortality.

I am mystified by those who would ignore the preponderance of the evidence and instead choose to believe weak outlier studies.

The FraminghamHeart Study proved, as far as I am concerned, that high cholesterol, especially LDL cholesterol, increases heart disease risk. The Framingham study helped establish the role of cholesterol.

“The study began in 1948 and the participants have continued to be followed over the decades. By the late 1990s, the study had accumulated over 50,000 cohort-years of follow-up data. This large cohort followed long-term over many decades contributed to the landmark discoveries linking major cardiovascular risk factors like smoking, blood pressure, and cholesterol to heart disease outcomes.”

A similar large longitudinal cohort study in Denmark known as the Copenhagen City Heart Study. Initiated in 1976, the Copenhagen City Heart Study enrolled about 10,000 men and women aged 20-93 years old from Copenhagen. Participants were examined at baseline and followed for over 40 years, with several additional exams over time to update risk factor data."
And had virtually the same outcomes.

So are you saying that cholesterol control via statins has no significant benefits?


The issue is not cholesterol but the narrow minded simplistic focus on lowering LDL.
In the following post I used the official CVD 10 year risk calculator of the European Society of Cardiology and my LDL has doubled from 106 to 198mg/dl but my CVD risk is now lower.
The LabCorp NMR lipid panel also classifies me as low CVD risk.
None of those guys are cholesterol nor statin deniers BTW.

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European and American cardiologists differ in their calculators. If you plug in your values in the American calculator.!/baseline-risk

Your risk is 7.1.

I made some assumptions you’re male (higher risk) and white.

The views on LDL may differ as well.

It’s because the US has a lower life expectancy than Europe.
I’m in the US but I’m French so I used the low risk region EU risk calculator.

Here are all the calculators for various EU countries.

That said that’s a huge risk increase for the US calculator.
Note that if I plug the values with the lower LDL in the US calculator, I get 6.7% which is basically almost identical.

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