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Re: Statins - side effects

Posted: 16 Nov 2020, 11:57am
by roubaixtuesday
mjr wrote:
thirdcrank wrote:I see the so-called Nocebo effect has been reported again

Most statin problems caused by mysterious 'nocebo effect', study suggests

https://www.bbc.co.uk/news/health-54951648

Only 60 patients, many details subscription only, but a study design which excludes long-term accumulation effects and won't readily capture exercise-induced effects. The authors and journal should be ashamed of the damage they will do to patients' mental health with this.


Very odd comment.

How is it bad for mental health to understand more about what's going on?

Sure, the study could be larger, wider in scope and longer, but nevertheless, it shows very clear results, obviously beyond the level of statistical significance.

Re: Statins - side effects

Posted: 16 Nov 2020, 12:02pm
by Jdsk
mjr wrote:
thirdcrank wrote:I see the so-called Nocebo effect has been reported again

Most statin problems caused by mysterious 'nocebo effect', study suggests

https://www.bbc.co.uk/news/health-54951648

Only 60 patients, many details subscription only, but a study design which excludes long-term accumulation effects and won't readily capture exercise-induced effects. The authors and journal should be ashamed of the damage they will do to patients' mental health with this.

"N-of-1 Trial of a Statin, Placebo, or No Treatment to Assess Side Effects"
https://www.nejm.org/doi/full/10.1056/NEJMc2031173?query=featured_home

Adherence to statins is a big issue. A lot of potential health gains might be lost. There's a major, often heated, debate about side-effects. This is a useful contribution to what's going on.

The study size needn't be a problem if the effect is big enough and the design powerful enough. Analysis of this is routinely sought in advance by Research Ethics Committees.

There may well be time effects that take longer but that doesn't invalidate what was observed.

Jonathan

Edited: Crossed with above. SNAP!

Re: Statins - side effects

Posted: 16 Nov 2020, 12:07pm
by NATURAL ANKLING
Hi,
No I probly didn't word that very well, what I meant to say was that it's very difficult to reduce your cholesterol level on your own to a level where your GP is advised to not do anything about it?
but doing nothing about your lifestyle or not taking advice from professionals, is unfortunately the way for some people, We have all met them haven't we.

Re: Statins - side effects

Posted: 16 Nov 2020, 12:14pm
by Jdsk
Plasma total cholesterol concentration is very useful in risk calculation. But the concept of titrating it down within an individual to a safe level is very different. (And we once showed that repeat measurements are carried out far too frequently.)

Jonathan

Re: Statins - side effects

Posted: 16 Nov 2020, 1:40pm
by Tangled Metal
Twenty odd years ago I had an interview for a work placement/, masters degree/ research job in an engineering discipline. I was midway through interview when professor had a working lunch with some rolls Royce research boffins. It was amazing conversation I was party to. Apparently even engineering research projects and industrial engineering research employ statisticians to assess, advise, modify and approve research experiments. It was an extra income source for statistical lecturers, PhDs and research associates.

I have no doubt that if the researchers have any credibility they too will have designed their research and methodology using statistical methods to ensure robust research is carried out. Rubbish in rubbish out but with care and sufficient design input even small sample size can give a credible output. No expert but I've seen how quality research relies on good design of experiments. Or at least was a party to a conversation about it.

Re: Statins - side effects

Posted: 16 Nov 2020, 1:50pm
by Tangled Metal
Btw I had one of those well man clinics at my gp surgery. There's a program for it where the nurse ticks boxes according to your answer then once all answered its the next tab and new sets of questions. Apparently a half hour with bloods and pressure taken.

For me it was first question, next tab, second question, third tab. Things like do you smoke got negative as did have you ever smoked, equals next tab. How much exercise do you do a week, next tab. It became quite funny how with the 5 minutes blood and pressure I was out within 10 minutes.

Three or four weeks later receptionist told me everything ok. Apparently my cholesterol was high but my ratios were right so no problem.

There's a family history of high cholesterol but after the NHS started checking levels of different cholesterol types my family history became low dangerous type and high good type. Seems a high good type helps keep the bad type down or so we all got told. Before the ratio was measured my mum nearly got put on statins because cholesterol was high. Not after ratio tested.

As you can tell, I really don't know enough about cholesterol. I just know it's likely to not become a real issue until I'm a lot later in life, say late 60s or early 70s.

Re: Statins - side effects

Posted: 16 Nov 2020, 5:10pm
by mjr
roubaixtuesday wrote:
mjr wrote:
thirdcrank wrote:I see the so-called Nocebo effect has been reported again

Most statin problems caused by mysterious 'nocebo effect', study suggests

https://www.bbc.co.uk/news/health-54951648

Only 60 patients, many details subscription only, but a study design which excludes long-term accumulation effects and won't readily capture exercise-induced effects. The authors and journal should be ashamed of the damage they will do to patients' mental health with this.


Very odd comment.

How is it bad for mental health to understand more about what's going on?

I never said it was. Maybe that misinterpretation is why you think it an odd comment.

The damage to mental health will come from news reports about this study being used to browbeat some patients who experienced real side-effects into attempting statin therapy again, not only by medics (not the experts in hospitals and not even the better GPs, but there will be some GPs who are influenced by this), but by ordinary people, maybe family, who see this reported in the news and tell someone who came off statins when they suffered memory problems or could no longer stand up that it was all in their mind and they were imagining it all.

Many of those patients already have mental and/or physical scars from their experience with statins. I certainly do. I know I'm a bit excitable about this — but I'm not sure you'll find someone who's missing years of memory who doesn't find it a bit unjust and want others to avoid the same fate. It's not often people recover from such things.

The study looks weak/niche and the reporting seems worse. For example, the BBC headline is "Most statin problems caused by mysterious 'nocebo effect', study suggests" but I'm pretty sure that the authors weren't considering "most statin problems" (I see no analysis in the public materials of what problems have what prevalence, for example) rather than simply looking for any reported short-term side-effects, so most of that headline is the reporter's invention.

It's a small study with pretty tight selection criteria (described below - the 60 in the study were all that were used from a pool of about 300 potential participants). Could anyone really defend the BBC headline?
Sure, the study could be larger, wider in scope and longer, but nevertheless, it shows very clear results, obviously beyond the level of statistical significance.

The small sample mainly means that the study won't tell us much about "most statin problems" because many of the long list of known problems occur in 1% or less of patients, at least according to statin patient information leaflets.

But more than that, the design looks seriously flawed to me, both based on my education as a statistician and my experience as a patient. It can be scarily easy to get statistical significance for what is arguably a rewording of a null hypothesis (no effect) with a bad design. It's worth remembering that most of the classical statistical methods are based around proving that there probably wasn't no effect (rejecting the null hypothesis), so it's hotly debated how well they work for actually finding evidence for no effect.

On top of that, the participant selection criteria (Appendix S1) only includes patients who withdrew from statins because of perceived side effects developed within 2 weeks of starting taking them. The exclusion criteria also excludes anyone who suffered side effects taking more than 2 weeks to present, as well as a list of the most serious side effects. So people like me already wouldn't be in this study. There was also a catch-all option to exclude anyone the study doctor judged should not be enrolled.

It reads like patients had to go to Hammersmith Hospital twice. That could also bias the study. Of the 222 of 308 possible participants who declined to attend, 24 gave travel as an explicit reason, but I suspect it may have been a factor in the 31 "too busy", the 22 who gave no reason and some of the others like "anxiety about travelling to site". It also seems a bit suspicious to me that no-one declined due to it being a smartphone-app-based study, which makes me wonder what was in the recruitment adverts.

The drug and dose was Atorvastatin 20mg, which means that it's probably limited to medium-or-higher risk patients, not the far larger population taking a 5 or 10mg dose daily. It's stated elsewhere that their average LDL-C is just 4.16mmol/L.

And it's downright curious to me that none of the list of adverse events look like typical oft-reported statin problems that I've heard about at patient forums. Did the participant selection criteria effectively exclude those who suffer real statin side-effects?

There are more questions than answers... but the people who will promote this study hardest don't seem to be interested in the questions, only their preferred answer.

Re: Statins - side effects

Posted: 16 Nov 2020, 5:22pm
by roubaixtuesday
Mjr,

I'm sorry to hear of your issues with statin intolerance, and I certainly in no way wish to diminish or challenge them in any way whatsoever.

But...

The authors and journal should be ashamed of the damage they will do to patients' mental health with this


And

The damage to mental health will come from this study being used to browbeat some patients...


Even if the second quote were true, it doesn't in any way justify your condemnation of the researchers in the first.

However incomplete and imperfect the study - and all research is - the results still seem a valuable addition to understanding of statin intolerance symptoms.

Re: Statins - side effects

Posted: 16 Nov 2020, 5:24pm
by Jdsk
mjr: I think it would help readers if you could recast that into separate sections of comments on the reported study, the BBC reporting and your opinions of its likely effects on future practice.

And could you confirm that you are telling us that you are missing years of memory which you think was caused by a statin.

Thanks

Jonathan

EDITED: crossed with above post.

Re: Statins - side effects

Posted: 16 Nov 2020, 5:35pm
by mjr
Jdsk wrote:And could you confirm that you are telling us that you are missing years of memory which you think was caused by a statin.

I am pretty cross about the above language which implies that the harm I suffered was not due to atorvastatin, but only that I "think" it was.

Please remember that I am not a stereotypical statin naysayer. I tried to take them, I really did. Even after being taken off atorvastatin, I spent the best part of a decade trying to find some way of taking some statin that didn't cripple me, with expert medical support, ultimately without success

I may re-edit the earlier post once I have calmed down.

Re: Statins - side effects

Posted: 16 Nov 2020, 5:38pm
by mjr
roubaixtuesday wrote:Even if the second quote were true, it doesn't in any way justify your condemnation of the researchers in the first.

However incomplete and imperfect the study - and all research is - the results still seem a valuable addition to understanding of statin intolerance symptoms.

Such a flawed study does not add much understanding and I suspect it will not outweigh the harm. For now I will stand by my condemnation because I believe scientists have a responsibility to consider the reasonably-likely consequences of how they publish. I wonder about contacting those overseeing the ethics of this, as well as the BBC Complaints service about their misleading headline.

Re: Statins - side effects

Posted: 16 Nov 2020, 5:51pm
by roubaixtuesday
mjr wrote:... the above language which implies that the harm I suffered was not due to atorvastatin, but only that I "think" it was.



I don't think this is true at all.

Just because most side effects reported in this trial were not down to the active doesn't at all mean that all side effects are not, and I don't think a single doctor would think that.

The BBC headline seems entirely reasonable if most statin side effects are reported soon after starting therapy. I have no idea if that's true or not.

There's nothing unethical about the study whatever, you'll get nowhere complaining on those grounds.

Re: Statins - side effects

Posted: 16 Nov 2020, 6:08pm
by mjr
roubaixtuesday wrote:The BBC headline seems entirely reasonable if most statin side effects are reported soon after starting therapy. I have no idea if that's true or not.

I've never seen a study claiming that most are reported within 2 weeks and it's not my experience with either patient forums or relatives. More importantly, the published report doesn't say they are and the BBC cites no other source for it.

There's nothing unethical about the study whatever, you'll get nowhere complaining on those grounds.

I think the selection criteria may be arguable.

Re: Statins - side effects

Posted: 16 Nov 2020, 8:02pm
by Mick F
My OP.

The rest is history as far as I'm concerned.
Perfectly well now.

Mick F wrote:If you read about the common side effects of taking statins, it reads like a list of what I'm suffering from.
http://www.nhs.uk/Conditions/Cholestero ... fects.aspx

I have a large familial cholesterol problem and have been taking huge rugby balls of statins every day for maybe 10 years. As I've become older, I'm obviously feeling my age, but headaches are ever present (some of them are severe), I often get indigestion, my joints ache especially ankles and elbows, I get the odd nosebleed when I blow my nose, and my nose seems to continually run a bit, plus often I have an achey throat.

I've decided that for the whole of June, I'm not going to take my daily dose of Atorvastatin 80mg and see how I get on.
If any or all of the above symptoms disappear, I'll have to make my mind up about quality of life vs cholesterol reduction.

I see myself as a fit and healthy person as I'm certainly not a couch potato, overweight slob. :D

Re: Statins - side effects

Posted: 16 Nov 2020, 8:30pm
by NATURAL ANKLING
Hi,
There is one thing for sure most of these blood meds are crippling for endurance / highish level exercise!
I just wish I could afford to get off them :(