"Don't stop the statin!"

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"Don't stop the statin!"

Post by GeenDienst » Mon Dec 30, 2019 11:08 am

Their "!", not mine.

An editorial on why people should take their statin, and weighing in against the statin denialists, including the kind of media conspiracies that tend to get you lot all excited.

Free.

https://academic.oup.com/eurheartj/arti ... 26/5565263
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Re: "Don't stop the statin!"

Post by JQH » Mon Dec 30, 2019 2:46 pm

I did stop the statins about three years ago when muscle pains started. As it turns out, that wasn't myalgia but Parkinsons. However, in that period I stopped working and my cardio symptoms disappeared.
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Re: "Don't stop the statin!"

Post by GeenDienst » Mon Dec 30, 2019 3:12 pm

As it happens, studies using randomised, blinded rechallenge with statins show that most reported muscle side-effects weren't to do with a statin.

https://www.sciencedirect.com/science/a ... 9717389660
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Re: "Don't stop the statin!"

Post by FredM » Sun Jan 05, 2020 10:28 am

Very useful as I’m scheduled for a statin and aspirin prescription review. Will cite this study and suggest to GP that I stick with statin and (probably) drop aspirin.

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Re: "Don't stop the statin!"

Post by Herainestold » Sun Jan 05, 2020 6:09 pm

Didn't a certain Curly Haired Physician write a very skeptical book about statins and how the Pharma Cos played fast and loose with the data on side effects? There is a lot of contrary info on the effects of these drugs, I would certainly think more than twice about taking them.
Comparison with real-life clinical experience
Many real-world patients report muscle-related symptoms with statins. This contrasts with the low placebo subtracted rate in blinded trials shown in this meta- analysis. Several explanations are possible. First, commercial sponsors of clinical trials may not be motivated to search exhaustively for potential side effects. One pointer towards this is that, although liver transaminase elevation was documented in the majority of trials, new diagnosis of diabetes was only documented in three of the 29 trials. It is also likely that side effects data is collected, but not reported in the academic paper: a recent study by IQWiG, the German government’s cost effectiveness agency, found complete information for 87% of adverse event outcomes in the standard lengthy regulatory document for industry trials (the Clinical Study Report) but for only 26% of adverse event outcomes in the journal publication [Wieseler 2014]. Second, many trials do not state clearly how and how often adverse effects were assessed….
Wieseler B, Wolfram N, McGauran N, Kerekes MF, Vervölgyi V, Kohlepp P, et al. Completeness of Reporting of Patient-Relevant Clinical Trial Outcomes: Comparison of Unpublished Clinical Study Reports with Publicly Available Data. PLoS Med. 2013 Oct 8;10(10):e1001526.
https://www.science20.com/interwebometr ... ain-132368

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Re: "Don't stop the statin!"

Post by GeenDienst » Sun Jan 05, 2020 8:49 pm

There are dozens of well powered randomised controlled trials that underpin the benefits or statins for reducing the risk of adverse cardiovascular outcomes. Their efficacy and safety profiles are well understood, probably better than any other medicine. The liver transaminases issue is an old concern, rarely a problem, and the whole thing is easily managed. They do cause a small rise in blood glucose, very occasionally triggering the categorical diagnosis of type 2 diabetes if it nudges over the cut-off, in people who were heading for type 2 diabetes anyway. The literature is clear that the cardiovascular benefits of statins outweigh any risks even here. Meta-analyses have confirmed all this.

Take or don't take what you want, not my problem. But the benefits and lack of harm from statins is is as evidence-based medicine as it gets. It's all in the review I cited.
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Re: "Don't stop the statin!"

Post by Herainestold » Mon Jan 06, 2020 2:56 am

Pharma is making billions from statins.

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Re: "Don't stop the statin!"

Post by JQH » Mon Jan 06, 2020 9:00 am

Herainestold wrote:
Mon Jan 06, 2020 2:56 am
Pharma is making billions from statins.
That may be true but the discussion here is about the scientific evidence supporting their use.
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Re: "Don't stop the statin!"

Post by murmur » Mon Jan 06, 2020 11:23 am

Herainestold wrote:
Mon Jan 06, 2020 2:56 am
Pharma is making billions from statins.
Commercial enterprises make money! Shock! Horror! Probe!

In other news Pope's religious affiliations confirmed and toilet habits of bears revealed.

Do you actually have a point in posting that?

PS Boiron makes billions from sugar pills and slightly impure water.
It's so much more attractive inside the moral kiosk

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Re: "Don't stop the statin!"

Post by GeenDienst » Mon Jan 06, 2020 11:57 am

The clinical evidence that statins are safe and effective is overwhelming. There are only two side-effects worth a damn, the small increase in blood glucose, and, uncommonly, drug-related muscle aches. Both are well understood, and I have already shown you reviews of the evidence that they do not anywhere negate the benefits of the treamtent. The latter have been studied in well-designed randomised trials conducted specifically to study their incidence and relation to statin treatment.

These drugs help to keep people alive. We really don't need some evidence-free c.nt spreading handwavy bollocks that could dissuade someone from taking such a medicine. The particular handwavy c.nt we have here doesn't even seem to know that statins are generic.

Bring something substantive, Herainsetold, or shut the f.ck up.
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Re: "Don't stop the statin!"

Post by Pucksoppet » Mon Jan 06, 2020 11:59 am

GeenDienst wrote:
Sun Jan 05, 2020 8:49 pm
There are dozens of well powered randomised controlled trials that underpin the benefits or statins for reducing the risk of adverse cardiovascular outcomes. Their efficacy and safety profiles are well understood, probably better than any other medicine. The liver transaminases issue is an old concern, rarely a problem, and the whole thing is easily managed. They do cause a small rise in blood glucose, very occasionally triggering the categorical diagnosis of type 2 diabetes if it nudges over the cut-off, in people who were heading for type 2 diabetes anyway. The literature is clear that the cardiovascular benefits of statins outweigh any risks even here. Meta-analyses have confirmed all this.

Take or don't take what you want, not my problem. But the benefits and lack of harm from statins is is as evidence-based medicine as it gets. It's all in the review I cited.
It's the green jelly bean problem, but on a trial basis.
The issue is, while there may be many positive trials, we don't know how many non-positive ones have simply not been published, which is what motivated Ben Goldacre to start pushing for mandatory open registration of all trials and recording their outcomes.
The case for statins on a population/public health basis seems very clear. But if only trials with good outcomes for the pharmaceutical companies get published, one begins to wonder if there is a rodent-like odour emanating from somewhere.
I don't know the truth here, and it is arguable if anybody does. Which is a problem.
Unfortunately, the solution requires a fundamental restructuring of how research is conducted, and how academic work gets rewarded, so that replication becomes important, and negative results don't besmirch careers. This will not happen quickly, if at all.
The argument over statins is a good example of absence of evidence (of side effects) not necessarily being evidence of absence (of side effects). How do you know that adverse trial results have not been suppressed?

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Re: "Don't stop the statin!"

Post by GeenDienst » Mon Jan 06, 2020 12:20 pm

Pucksoppet wrote:
Mon Jan 06, 2020 11:59 am

The argument over statins is a good example of absence of evidence (of side effects) not necessarily being evidence of absence (of side effects). How do you know that adverse trial results have not been suppressed?
No, it isn't. The Cholesterol Treatment Trialists’ (CTT) Collaboration has a database of 175,000 patients. That's plenty to show no association between statins and serious adverse outcomes. And:
if randomised trials have already reported results based on large numbers of occurrences of a particular outcome (as with muscle-related outcomes in statin trials; appendix) then the inclusion of any unpublished data from other trials that did record such outcomes is not likely to materially alter the assessment of the effect of the treatment on that outcome
There is a huge database of evidence on statins. The CTT Collaboration, for example, is working with patient-level data from 30 randomised, controlled trials, all powered and of sufficient duration to show effects on hard clinical outcomes. You would need to be postulating an absolute f.ckload of unpublished radnomised, controlled, Phase III trials to alter that. It's simply untenable.

And as I've said, the muscle issue has been identified from these data, and studied in its own, dedicated randomised trials in recent years.

And there's the other point that Goldacre never seemed to make - even in the hugely unlikely event that a Phase III CV outcomes trial is unpublished (and we would need to see examples of this, you can't hide an investigator-led, three-to-five year trial in hundreds or thousands of patients very easily), the regulators still get to see the data from those trials.

Here, we're way beyond quietly forgetting the odd Phase II trial here and there.
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Re: "Don't stop the statin!"

Post by Pucksoppet » Mon Jan 06, 2020 12:22 pm

To continue:

An answer might be determining how 'well powered' a trial has to be to be certain you are seeing a real result given that and unknown number of trials that don't give that result remain unpublished. For all I know, existing trials are 'well powered' enough, and did actually look properly for adverse effects.

I know I may be coming across as a conspiracy theorist, talking about 'suppressed' trials, but the problem appears systemic: non-positive trial results don't see the light of day.

Now it is obviously expensive to spend money on trials simply to not publish them if they don't give you the outcome you are looking for, and I seriously doubt people are explicitly hiding trials: too many people are involved, so I doubt there is some big pharma executive cackling evilly somewhere looking to see how to mislead regulators. On the other hand, the system as currently operated, does appear prone to positive bias.

This is where I think people like Ben Goldacre and Nicholas Brown are important in trying to hold things to account, and I wish there were many more like them.

Oh - and thank-you for your posting in-between mine.

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Re: "Don't stop the statin!"

Post by GeenDienst » Mon Jan 06, 2020 12:25 pm

Phase III trials see the light of day. The companies announce them in advance, include their designs in their satellite symposia, and generally make a big deal about how they are running them. Then, they are large, long, and investigator led. I have no idea how you would start to go about suppressing a phase III trial.

I accept your point about smaller trials, but outcomes trials are simply too big and obvious for this. And we have 30 of them, able to provide patient-level data. The lesson if any is that we probably need more outcomes trials in other fields of medicine (NB: the FDA now mandate this for diabetes drugs).

In a different field, AstraZennopod once declined to formally analyse and publish a Phase III trial on a cancer agent, where the active drug had a bit of a death problem and the trial was stopped early. The investigators were not pleased, but everyone knew what had happened.
Last edited by GeenDienst on Mon Jan 06, 2020 12:36 pm, edited 2 times in total.
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Re: "Don't stop the statin!"

Post by Pucksoppet » Mon Jan 06, 2020 12:34 pm

I'm trying very hard not to come across as a conspiracy theorist.

I agree with you that Phase III trials would be difficult to hide, and if I claimed they were being routinely hidden, I would definitely need to have evidence.

I don't.

On the other hand, I hope you agree that there is a problem at the early stages of research where negative results tend not to get published, and replication is often deprioritised. It's actually in pharma companies interests for basic research to be of good quality so they don't spend resources chasing rainbows.

I hope we are in danger of agreeing violently.

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Re: "Don't stop the statin!"

Post by GeenDienst » Mon Jan 06, 2020 12:35 pm

Pucksoppet wrote:
Mon Jan 06, 2020 12:34 pm

I hope we are in danger of agreeing violently.
Step outside and say that.
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Re: "Don't stop the statin!"

Post by Gentleman Jim » Mon Jan 06, 2020 12:46 pm

If anything, statins are billion sellers despite Pharma, not because of it.
When statins first emerged, I know or know of, several highly placed managers in sales/marketing for several multinationals, who described them as "a drug looking for a disease to treat"
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Re: "Don't stop the statin!"

Post by GeenDienst » Mon Jan 06, 2020 2:02 pm

Gentleman Jim wrote:
Mon Jan 06, 2020 12:46 pm
When statins first emerged, I know or know of, several highly placed managers in sales/marketing for several multinationals, who described them as "a drug looking for a disease to treat"
I knew a research HoD for the UK discovery effort of a company you've certainly heard of who advised them to not go for an ACE inhibitor, because most hypertensives aren't renin dependent. That turned out to be career limiting and retirement promoting.
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Re: "Don't stop the statin!"

Post by dyqik » Mon Jan 06, 2020 2:09 pm

Gentleman Jim wrote:
Mon Jan 06, 2020 12:46 pm
If anything, statins are billion sellers despite Pharma, not because of it.
When statins first emerged, I know or know of, several highly placed managers in sales/marketing for several multinationals, who described them as "a drug looking for a disease to treat"
If you are going down the "BigPharma business imperative" conspiratorial mumblings route, Big Pharma would probably really like to find minor but somewhat significant side-effects with their patented drugs about 5 years after they go to market, so they can patent and release replacement variants that get onto the recommended drugs lists before the original drug's patent expires, but still have time to get a good return on the original drug.

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Re: "Don't stop the statin!"

Post by GeenDienst » Mon Jan 06, 2020 2:19 pm

I think Mr Jim was going down the opposite route. And it's too late for statins, which are already generic, including the more potent ones.

And the next big thing is already here - PCSK9 inhibtors. Huge cholesterol reductions, proven outcome benefits, very good safety and tolerability so far (better than statins). But, they are so expensive they are limited on t'NHS to people like those with familial hypercholesterolaemia (the kind that keel over at 41) who are already uncontrolled on or can't take a statin. When they go biosimilar, they will be much more widely used. One 2-weekly injection from a custom-designed injector pen, piece of piss.

Free review here:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6380691/
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Re: "Don't stop the statin!"

Post by FredM » Mon Jan 06, 2020 7:39 pm

Incidentally, off-patent generic statins are dirt cheap. Mine currently cost the NHS 91p/month.

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Re: "Don't stop the statin!"

Post by Herainestold » Mon Jan 06, 2020 9:15 pm

murmur wrote:
Mon Jan 06, 2020 11:23 am
Herainestold wrote:
Mon Jan 06, 2020 2:56 am
Pharma is making billions from statins.
Commercial enterprises make money! Shock! Horror! Probe!

In other news Pope's religious affiliations confirmed and toilet habits of bears revealed.

Do you actually have a point in posting that?

PS Boiron makes billions from sugar pills and slightly impure water.
All those billions are a huge incentive for Pharma to cheat, hide negative trials, ignore side effects et cetera.
Imagine those billions used to discover new treatments for marginalized POC patients instead of lifestyle enhancements for wealthy white males.

What would a post capitalist Pharma regime look like? Universities doing basic research and publicly funded, not profit based, entities choosing which treatments to test and designing transparent trials where both negative and positive results are published. How do we get there from here?

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Re: "Don't stop the statin!"

Post by dyqik » Mon Jan 06, 2020 9:16 pm

Herainestold wrote:
Mon Jan 06, 2020 9:15 pm
murmur wrote:
Mon Jan 06, 2020 11:23 am
Herainestold wrote:
Mon Jan 06, 2020 2:56 am
Pharma is making billions from statins.
Commercial enterprises make money! Shock! Horror! Probe!

In other news Pope's religious affiliations confirmed and toilet habits of bears revealed.

Do you actually have a point in posting that?

PS Boiron makes billions from sugar pills and slightly impure water.
All those billions are a huge incentive for Pharma to cheat, hide negative trials, ignore side effects et cetera.
No, it's not.

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Re: "Don't stop the statin!"

Post by Herainestold » Mon Jan 06, 2020 9:31 pm

dyqik wrote:
Mon Jan 06, 2020 9:16 pm
Herainestold wrote:
Mon Jan 06, 2020 9:15 pm
murmur wrote:
Mon Jan 06, 2020 11:23 am


Commercial enterprises make money! Shock! Horror! Probe!

In other news Pope's religious affiliations confirmed and toilet habits of bears revealed.

Do you actually have a point in posting that?

PS Boiron makes billions from sugar pills and slightly impure water.
All those billions are a huge incentive for Pharma to cheat, hide negative trials, ignore side effects et cetera.
No, it's not.
Why are they doing it then? For the lulz?

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Re: "Don't stop the statin!"

Post by GeenDienst » Mon Jan 06, 2020 9:40 pm

I've told you, Herainestold, bring something better than your handwavy conspiracy bollocks or f.ck the f.ck off.

I've had a very interesting discussion with Pucksoppet about how non-publication of trials isn't going to influence the clinical database on statins. You've brought nothing.
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