Cycling UK Forum

Anyway ...................

It's Repatha Friday for me tomorrow.

This is from 2016 during my time of refusing to take statins again, and before I started on the Repatha.
Sorry, I have no scan of a recorded results since then, but there isn't anything "abnormal" and I have zero side-effects.

roubaixtuesday wrote: ↑29 Jun 2023, 3:12pm 60-70% seems to apply in the non-statin population studied there too.

I need more time with a bigger screen to read the MENDEL-2 paper http://dx.doi.org/10.1016/j.jacc.2014.03.018 properly (including converting the units from US to EU) but it looks like Repatha alone is more like 50-60% than 60-70% - the graph you posted shows MENDEL-2 labelled as 20110114 and it seems to be some sort of reinterpretation looking at only measurements after 10 and 12 weeks. As you can see on the graph the MENDEL-2 mean is 60%, not 70%, but even that seems surprisingly high compared to what I was told to expect from Praluent and Linvoq.

A first glance at the appendix to the MENDEL-2 paper has noticed that the exclusion criteria includes "use of lipid-regulating drugs within 3 months." A list of disqualifying drugs isn't given, but I think it means anyone taking Ezetrol/ezetimibe was excluded, which would have been most statin-intolerant people with high/very-high cholesterol levels whose doctors were following the guidance. No wonder that gem is hidden in a 4-page Word Document for no apparent reason instead of being included in the main text. If you tilt the playing field by biasing the sample pool, great-looking results aren't as reliable!

I guess that exclusion may have been demanded by an ethical advisor, because accepting people taking ezetimibe already would have resulted in some of them having meds replaced by placebos for the duration of the trial, which could be slightly detrimental to their health, but surely the study could have been redesigned to accommodate that, or the potential participants asked whether they wanted to accept the risk. It's disappointing that a chance seems to have been missed to study the effect on those who might benefit the most.

mjr wrote: ↑29 Jun 2023, 11:59pm

roubaixtuesday wrote: ↑29 Jun 2023, 3:12pm 60-70% seems to apply in the non-statin population studied there too.

I need more time with a bigger screen to read the MENDEL-2 paper http://dx.doi.org/10.1016/j.jacc.2014.03.018 properly (including converting the units from US to EU) but it looks like Repatha alone is more like 50-60% than 60-70% - the graph you posted shows MENDEL-2 labelled as 20110114 and it seems to be some sort of reinterpretation looking at only measurements after 10 and 12 weeks. As you can see on the graph the MENDEL-2 mean is 60%, not 70%, but even that seems surprisingly high compared to what I was told to expect from Praluent and Linvoq.

A first glance at the appendix to the MENDEL-2 paper has noticed that the exclusion criteria includes "use of lipid-regulating drugs within 3 months." A list of disqualifying drugs isn't given, but I think it means anyone taking Ezetrol/ezetimibe was excluded, which would have been most statin-intolerant people with high/very-high cholesterol levels whose doctors were following the guidance. No wonder that gem is hidden in a 4-page Word Document for no apparent reason instead of being included in the main text. If you tilt the playing field by biasing the sample pool, great-looking results aren't as reliable!

I guess that exclusion may have been demanded by an ethical advisor, because accepting people taking ezetimibe already would have resulted in some of them having meds replaced by placebos for the duration of the trial, which could be slightly detrimental to their health, but surely the study could have been redesigned to accommodate that, or the potential participants asked whether they wanted to accept the risk. It's disappointing that a chance seems to have been missed to study the effect on those who might benefit the most.

You've just been through a series of posts where you've dived into medical information and completely misinterpreted the published data.

You follow this up with an attempt to impugn the motives of researchers.

There are many reasons to design the study the way it was. You have zero insight into why the choices were made.

Could I suggest that given your attempts to interpret the results of studies are so wide of the mark, your understanding of the design of studies might be equally so.

mjr wrote: ↑29 Jun 2023, 11:59pm

roubaixtuesday wrote: ↑29 Jun 2023, 3:12pm 60-70% seems to apply in the non-statin population studied there too.

A first glance at the appendix to the MENDEL-2 paper has noticed that the exclusion criteria includes "use of lipid-regulating drugs within 3 months." A list of disqualifying drugs isn't given, but I think it means anyone taking Ezetrol/ezetimibe was excluded, which would have been most statin-intolerant people with high/very-high cholesterol levels whose doctors were following the guidance. No wonder that gem is hidden in a 4-page Word Document for no apparent reason instead of being included in the main text. If you tilt the playing field by biasing the sample pool, great-looking results aren't as reliable!

For one thing, it says in the actual paper you linked

Eligible patients could not have used lipid-regulating drugs within 3 months of enrollment.

Not so hidden after all.

For another, it was literally the purpose of the trial to examine this for people who do *not* have a history of statin intolerance.

MENDEL-2 (Monoclonal Antibody Against PCSK9 to Reduce Elevated LDL-C in Subjects Currently Not Receiving Drug Therapy for Easing Lipid Levels-2). The trial was designed to evaluate the efficacy and safety of biweekly and monthly evolocumab at doses anticipated for use in clinical practice in a large population of patients with primary hypercholesterolemia not confounded by statin use or a history of statin intolerance.

There are other studies where they are used in combination with statins or for people with a history of statin intolerance.

for example:
in combination with statins https://pubmed.ncbi.nlm.nih.gov/31116355/
for patients with a history of statin intolerance https://www.sciencedirect.com/science/a ... 9714017288

Vorpal wrote: ↑30 Jun 2023, 9:44am For one thing, it says in the actual paper you linked

Eligible patients could not have used lipid-regulating drugs within 3 months of enrollment.

Not so hidden after all.

I feel that's ambiguous when the actual criteria was "must not have used..."

For another, it was literally the purpose of the trial to examine this for people who do *not* have a history of statin intolerance.

MENDEL-2 (Monoclonal Antibody Against PCSK9 to Reduce Elevated LDL-C in Subjects Currently Not Receiving Drug Therapy for Easing Lipid Levels-2). The trial was designed to evaluate the efficacy and safety of biweekly and monthly evolocumab at doses anticipated for use in clinical practice in a large population of patients with primary hypercholesterolemia not confounded by statin use or a history of statin intolerance.

Yeah, I misinterpreted that as the study evaluating efficacy and safety not confounded by those effects, rather than the patient population not having those things.

There are other studies where they are used in combination with statins or for people with a history of statin intolerance.

for example:
in combination with statins https://pubmed.ncbi.nlm.nih.gov/31116355/
for patients with a history of statin intolerance https://www.sciencedirect.com/science/a ... 9714017288

Sorry but I don't have time to read that all right now. I must go to the hospital. I'll return to it later.

roubaixtuesday wrote: ↑30 Jun 2023, 12:54pm All the information you are interested in seems to be readily available.

So where did you find the list of excluded drugs and reasoning?

mjr wrote: ↑30 Jun 2023, 12:55pm

roubaixtuesday wrote: ↑30 Jun 2023, 12:54pm All the information you are interested in seems to be readily available.

So where did you find the list of excluded drugs and reasoning?

Sure, the reasoning is in the introduction "Because anti-PCSK9 antibodies may offer a therapeutic option for patients on or off statin therapy, the MENDEL-2 (Monoclonal Antibody Against PCSK9 to Reduce Elevated LDL-C in Subjects Currently Not Receiving Drug Therapy for Easing Lipid Levels-2) trial was designed to evaluate the efficacy and safety of biweekly and monthly evolocumab at doses anticipated for use in clinical practice in a large population of patients with primary hypercholesterolemia not confounded by statin use or a history of statin intolerance."

And all lipid lowering agents are excluded.

Argue nicely, please

Found this.
I'd been on Repatha injections for three years by then.

re_cycler wrote: ↑24 Jun 2023, 1:06pm NICE patient guidance for deciding if you want to take a statin.

https://www.nice.org.uk/guidance/cg181/ ... -243780159

( apologies if it's been linked previously )

BEST bit of information!

QRISK of 40% is the worst they list....whatever that means...40% of what?
However, if you have 40% QRISK, over 10 years they would expect;
60% of people get no heart disease or stroke
25% get heart disease or stroke DESPITE TAKING STATINS
15% protected from heart disease& stroke by taking statins.

QRISK of 8% is the least they list
over 10 years they would expect
92% get no heart disease or stroke
5% get heart disease or stroke DESPITE TAKING STATINS
3% protected from heart disease/stroke by taking statins.

Several other QRISK percentages are listed

So, the percentage of people whom statins would be expected to protect is in all cases less than the percentage who would be expected to get the disease despite the statins

Doesn't seem a very effective treatment to me.

My conclusion is unaltered;
If you can take statins with no side effects, go ahead and take them.....I did for very many years.
Now, if I take the things for about a week, I then can't reach my feet to put my socks on....
So, I'm refusing statins, and this information from NICE has reinforced that decision.

Here's a doctor talking about cholesterol, statins and some mistakes made, https://youtu.be/iddFlIcxQi4?t=408

He appears sceptical of their use, especially in females and older people. This observational study https://pubmed.ncbi.nlm.nih.gov/24094647/ concludes: Among older people, cholesterol levels were unrelated to mortality between the ages of 70 and 90

180th Injection Friday tomorrow.
180 once a fortnight = nearly seven years.

Still no side effects, but I'm getting older.

180th injection done this morning.

In the post today was a letter from my specialist at Derriford Hospital Plymouth, discharging me and back to our local health centre.
There's info about my latest (stable) blood-test results.

For the past seven years, Derriford have been organising a courier to deliver my Repatha in packs of six - (twelve weeks worth) - but now our local health centre is getting the job. No doubt I have to go and collect them, but I do NOT want to go there every two weeks to collect an individual single unit.

I'll be getting in touch with them next week or so to ask what's going to happen. Best thing is to make an appointment with my doctor for a chat. After this morning's injection, I have three left. That's six more weeks of injections - last one of this batch is due 8th September - so I have time to sort this out.