Bravo, SM keeps delivering the most thoughtful nuanced posts. I appreciate this response to what was posted on X. Thank you for the break down and for the introduction to "GOD and Statins". I want to read this. Not surprised with the results of the pool on the tube. Certainty is what most people crave even when it is impossible to attain. I think the body likes to hangout in the sweet spot adding anything that "targets" something can disrupt this sweet spot. 1-90 is more likely than the 91st. Keep them coming!
What is clear from all of this: stop using the term "misinformation", especially in relation to medicine. Physicians who throw that term at each other (and especially at patients) need to stop it. Very few things in medicine (especially true for primary prevention) are that cut and dried. And please don't any physician use the term "statin denier" in regard to a patient. Ever since the pandemic, when medicine divided down political party lines, this has become a thing. Patient autonomy reigns supreme - whatever decision a patient makes for themselves is the correct one. Physicians don't need to take affront if they decide contrary to what is recommended. This clearly supports that. And, yes, statins should be OTC.
After spending nearly 5 decades perusing information regarding the connection between nutrient intake and health outcomes, I'm reasonably certain that chronic excessive intakes of linoleic acid and arachidonic acid are major the underlying cause of heart diseases and cancers. Excerpt: "The Mediterranean diet is low in arachidonic acid and rich in healthy fats such as monounsaturated fats found in extra-virgin olive oil (EVOO), nuts and omega-3 fatty acids from fish, which has been shown to lower the risk of inflammation, heart disease, cancer, diabetes and obesity, and other degenerative diseases." (web search - Steve Blechman New red meat study)
Epidemiologists can tell that a plant-based diet reduces risk of chronic inflammatory diseases but they cannot explain why. Here's a clue: "The degree of fatty acid unsaturation of mitochondrial membrane lipids has been found to be one of those biochemical parameters that are most strongly correlated with longevity, when different species of mammals and birds are compared, with a low degree of fatty unsaturation being correlated with less lipid peroxidation and a longer normal life-span." (web search - Anna Haug Individual Variation)
Roughly 2400 years ago Plato compared rural and urban lifestyles. Comment on rural living: They will feed on barley-meal and flour of wheat, baking and kneading them, making noble cakes and loaves... they must have a relish-salt, and olives, and cheese, and they will boil roots and herbs such as country people prepare; for a dessert we shall give them figs, and peas, and beans; and they will roast myrtle-berries and acorns at the fire, drinking in moderation. And with such a diet they may be expected to live in peace and health to a good old age, and bequeath a similar life to their children after them."
Urban lifestyle: Plato mentioned "confectioners and cooks; and swineherds"...and "animals of many other kinds, if people eat them...And living in this way we shall have much greater need of physicians than before."
So, to avoid gradually accumulating arachidonic acid in adipose tissue, (the only reliable indicator of long term exposure), it is a good idea to limit intake of animal products, other than dairy, to a few meals a week.
Note also this warning from Proverbs 20:23, Be not among drunkards or among gluttonous eaters of meat, for the drunkard and the glutton will come to poverty, and slumber will clothe them with rags."
Then, there's this ancient warning in Proverbs 23: "1 When you sit down to dine with a ruler, Consider carefully what is before you, 2 And put a knife to your throat If you are a man of great appetite. 3 Do not desire his delicacies, For it is deceptive food."
Let the patient decide with all above material facts (presented in probabilistic benefit and certain cumulative harms or costs) like "informed consent" + known unknown of whether patient will ever benefit from "treating" an illness that may never happen
Even as a religious adherent to EBM, this is the inherent limitation. You get a hypothetical blockbuster treatment that reduces all cause mortality by 10% (ARR), with an NNT of 10…and it’s an obvious no brainer….but no patient lives 10 % longer. 1 lucky patient lives….and the other 9 undertook the intervention for nothing…and we have no way of knowing who is in which camp.
So it’s no surprise that in primary prevention…even when the average effect is one that merits adoption, the vast majority of people will end up gaining nothing, and the entirety of dichotomous effect/benefit will accrue to the lucky few.
It’s yet another reminder that we must remain humble in the face of how little we know. The Rumsfeld-Ian known unknowns.
I find these 'minimal improvements' arguments very unconvincing. Firstly I suspect that the "Cohen's kappa' of such interventions is relatively high- Cohen's kappa measuring improvement divided by how much improvement can be achieved. So a therapy that turns a 1-10,000 chance into a 1-1,000,000 would have a good kappa. I think that kappa is a good measurement.
Another point is that if there are numerous drugs that have small improvements in life expectancy, than together they provide good protection. Remember that numbers less than one raised to powers go to zero rather quickly !
A third point is a pov that I may have heard first in a much earlier post on this forum (or perhaps by Prasad), which is that as long as the treatments are benign and not expensive- why not ? My statin costs me zero dollars on a drug plan that costs me nothing. So why not take it ?
Finally, abstractly one in ninety doesn't sound like a lot, but if you are on a crowded bus and you are told that someone on that bus will die today, I think you will find it unnverving !
So let me ask John a very practical question. You have a patient in say the 60-70 year range with no cardiac signs or symptoms of any sort but a mildly elevated LDL with other markers basically normal ( total cholesterol, hdl, possibly Apo A and apoB, and an age appropriate coronary calcium CT score). At what point do you advise taking a statin especially if you know that say 12.5 mg Crestor every other day will lower the patient's ldl significantly. Is taking a statin at that point equivalent to house insurance or are the adverse risks still significant. That’s really the rub of the matter because it seem to me that we really don't know what an acceptable upper level for LDL is, and one therefore has to balance the potential benefits with the potential risks which presumably can vary quite a lot from patient to patient. In other words, EBM and RCT and NNT values are all very well but they apply to populations and not to an individual (as you rightly point out).
The other issue to consider is the harms of the intervention in terms of adverse events which may not be pleasant. Statins clearly are associated with adverse events. Taking vitamin C (nothing to do with cardiac disease prevention), on the other hand, when not taken in excessive doses has literally no adverse events. Same with many other supplements. So if somebody claims that vitamin C reduces the incidence of cardiac events you'd have nothing to lose by taking vitamin C. But the same is not necessarily true of statins. In other words, one might be better off just taking bergamot juice or extract to reduce LDL levels (and trials have shown modest, up to 20% reductions) rather than statins which clearly reduce cholesterol and LDL levls far more effectively but come with potential adverse effects.
This is my hypothesis. Those that don't eat a healthy diet , don't exercise, smoke and drink to much get great benefits from statins. Their markers are high BP (24 hour> 140/90) blood sugar (A1c> 6.5), cholesterol is less important. Those who are metabolic strong may be harm by statins: risk of diabetes, muscle loss and fall in GLP. We need better screening to determine those few who benefit from statins. (full disclosure, I take a low dose of statin to hedge against the chance that I am wrong). By the way Reaven's great observational study of 2021 is evidence for my hypothesis.
1 As DR Aseem Malhotra says after doing research of the industry research data , that lower LDL in people over 60 - the higher the all cause mortality . This negates the premise that treatment lowering LDL over time will improve health outcomes.
2 As already mentioned you have to look at NNH - harms and side effects together with NNT. The author Dr Mandrola in the comments says that Statin harms are very small. I disagree .
If side effects are negligible, why are so many reported in the statin patient leaflet?
If side effects are negligible, why do so many people stop taking statins?
If side effects are negligible, why does the NNH report two serious side effects – diabetes and muscle damage – as likely occurring in 1 in 50 and 1 in 10 people respectively. New research shows how statins reduce GLP-1 by more than 50% , also lower LDL has an Alzheimer risk.
If side effects are negligible, why does Professor Rory Collins (one of the major proponents of statins) co-own a patent for a genetic marker that identifies patients at increased risk of myopathy (muscular pain)? As reported in the Sunday Times: “The test, branded as Statin–Smart, is sold online for $99 (£76) on a website that claims 29% of statin users will suffer muscle pain, weakness or cramps. The marketing material also claims that 58% of patients on statins stop taking them within a year, mostly because of muscle pain”
3 We know how bad epidemiological and cholesterol research is , besides the conflict of interests and how medicine and research is being incentivized to deliver pre -ordered results.
Great piece, love the way that you laid out the explanation. A few comments:
--- I agree that care is needed when using misinformation/disinformation terms. However, the source and context around "the number" matters. If the clear goal is to get people who are likely beneficiaries to discontinue or not initiate statin therapy by deliberately biasing what you prevent, you've got a good case for disinformation
--- As we learn, we can revise guidelines for use of a therapy. Clinical trials usually don't have many subgroup analyses and aren't powered for them but additional data will be coming. Revised U S guidelines for statin therapy rule out or reduce the number recommended for statins given better risk stratification. No one is arguing to put them in the water anymore
--- I'm ex-Pharma and, yes, pharma wants to maximize profit. They want to have more patients on therapy longer to do this. However, they also need to get their drug approved and show that it works (hopefully really well). If I have poor patient selection criteria for my clinical trial, I may fail to show that my drug works. The first 2 anti-PD1 checkpoint inhibitors for cancer approached PD-1 expression differently for patient inclusion in trials which gave 1 of them a large competitive advantage
--- Expanding on the last point, personalized medicine is a goal, knowing the best treatment for you using genetic markers and other factors to maximize efficacy and limit risk
Appreciate this analysis. The bigger question, I think, is are these people patients? The reason insurance and flying are not apt comparisons is because those are transactions between a buyer and seller. Think about oncology. They frequently celebrate trials for terrible diseases that extend life weeks to months - these are breakthroughs! The cost per patient for treatment (idk exact numbers) is far greater than a statin. Yet we don’t have this conversation, because everyone agrees that those are patients in desperate need of help - and hope. Is an individual with high LDL and no other risk factors a patient with a disease? If so then all of this is critical and relevant, and I favor your interpretation of decision making. But if this is really just wellness disguised as medicine - then we either should make statins OTC or more seriously consider the value as specialists. With the pervasiveness of CAC scores and lipid panels I have not decided where I land on this question.
"They frequently celebrate trials for terrible diseases that extend life weeks to months - these are breakthroughs!"
It was probably around 1976 when my physician father (Family Practice) told me oncologists get really excited when a treatment extends a patient's life by one month. Even at age 20, I thought, "By that time, the cancer patient is really sick, and probably in considerable pain. Is there really a great net benefit for the patient in continuing to live another month? But there IS for the medical providers.
By the way, 44 years later, when my father was 91 and dying in the hospital, he had to STARVE HIMSELF TO DEATH to get around the hospital's overactive (and profitable) life extension procedures.
Cholesterol is not the cause of heart attacks. They are markers indicating inflammation. This is how Big Pharma has deceived the medical community for their profits. That is like saying the cause of house fires are the firemen. Yes firemen arrive at all fires, but they did not cause the fire. Statins are Implicated in muscle cramps, brain fog, and diabetes. They may also contribute greatly to Alzheimer's, The brain needs cholesterol to function. An independent (non-Big Pharma) study of 1 million people taking statins for 5 years, compared to 1 million not taking Statins showed the statin group lived 3 days longer. Big Pharma touts a RELATIVE decrease in heart attacks of 29 %, but the ACTUAL decrease is only 1%. That is bogus science. Also in 1985 normal cholesterol levels were 300. Statins came out in 1986 and the next year normal levels were arbitrarily decreased to 200 (I wonder why?) Statins are Big Pharma's number one drug ($20 Billion per year).
This is a huge problem in gender medicine in the US, where claims that questions regarding studies and statements about the weak certainty of evidence are "misinformation" or political. E.g., "Combating Scientific Disinformation on Gender-Affirming Care" in NEJM.
There are surely political actors and misinformation in the field, but also a lot of physicians and researchers doing due diligence and finding serious concerns regarding current practice vs medical best practice. Thus in Europe one has instead: "ESCAP statement on the care for children and adolescents with gender dysphoria: an urgent need for safeguarding clinical, scientific, and ethical standards " (ESCAP is an umbrella organization of child and adolescent psychiatry societies from over 30 European countries, https://pubmed.ncbi.nlm.nih.gov/38678135/ )
The evidence is similarly low and very low certainty for the other medical gender interventions for under 19 (and in some systematic reviews which go up to age 26).
Hoping the US journals and other US medical societies start following the evidence soon for this topic. It is already going to be hard for them to explain why they waited so long, to those who have (rightfully, in this topic!) lost trust in them.
I may be misunderstanding the meaning of such a skewed distribution, but doesn't the fact that 93% of men and 97% of women only have harms and no gains suggest that we don't understand well enough why/how the preventive therapy works--the mechanism, for whom it's appropriate, etc.? Isn't this a good argument for treating the problem when it appears and not ahead of time?
As a layman, I find this observation striking. What about those 7% of men and 3% of women is different from the others? This is where the car insurance analogy fails. As a driver, one can do everything the right way and still be involved in a collision because something out of one's control went wrong that day. For the statin situation, something about you, some prior condition or set of conditions, exist that lead you to an event but that statins seem to ameliorate. What is that prior condition or set of conditions?
Excellent! Well said. And now you should follow it with a NNT discussion that explains further. For instance, even if you isolate those who experience the anti-hypertensive benefit, 93% see no benefit—only harms and costs. Worth it? Interesting discussion. To me, the London Tube survey comparisons are fascinating, but maybe misleading, because there is no 'certainty' of gaining a short amount of time with any preventive treatment. How about if the survey was truer to primary prevention statin data for most people (risks <20% at 10 years). That would be a 0% chance of gaining one year versus a 0% chance of gaining more than that. Tough call? This is because only EXTRAPOLATIONS beyond trial durations 'find' any mortality benefit (and they may be wrong). For secondary prevention, best case scenario, it's a 1.2% chance of being in the group that sees a long term mortality benefit (possibly lasting 5-10 years) and it comes with a 2% chance of getting diabetes (a forever gift) plus all other harms and costs. Worth it? 99% chance no benefit? Tricky.
I'm surprised to see Dr. Mandrola using mathematical modelling as an argument against systematic review of clinical trials. It's Imperial College, for God's sake! With their track record, I wouldn't take their calculations as an argument to support anything.
Here is my argument. If the statin makers saw a chance that longer term statin taking improves the OS, they would make the trials longer. They would have an excellent argument for more sales. But they never did. So for me, any claim for better results on longer statin use is just a speculation. Unfounded speculation.
The study in BMJ Open actually shows the prolongation of life from - 10 to + 27 days. Median + 3 days for primary and + 4 days for secondary prevention.
I don't think you can exactly paint or tar Imperial College with a single brush after the good Dr. Neil Fergusson from Imperial managed to predict (willfully some might say) the impact of every epidemic/pandemic he has looked at completely wrong (not just Covid but also Mad Cow Disease and other infectious diseases). But people in other departments, such as cardiology, might be a lot more reliable and circumspect than Ferguson. Every instution has some bad players in it.
Perhaps there are better people around there. But they should speak up when Ferguson destroys reputation of the institution. It's always Imperial College with outrageous prediction. It's always helping to increase panic.
You do realize that Imperial College is just as big as Harvard or MIT. and Ferguson didn't destroy the reputation of Imperial. Ferguson destroyed his own reputation.
I know it's not fair. But I only hear about imperial college when a new epidemy starts and journalists are looking for a really juicy prediction how many people will die this time. And they are never disappointed, it's always a number for the front page. I'm aware that a reasonable number would probably get lost and that I might not hear about reasonable predictions from other IC departments. But that's where we are.
Bravo, SM keeps delivering the most thoughtful nuanced posts. I appreciate this response to what was posted on X. Thank you for the break down and for the introduction to "GOD and Statins". I want to read this. Not surprised with the results of the pool on the tube. Certainty is what most people crave even when it is impossible to attain. I think the body likes to hangout in the sweet spot adding anything that "targets" something can disrupt this sweet spot. 1-90 is more likely than the 91st. Keep them coming!
What is clear from all of this: stop using the term "misinformation", especially in relation to medicine. Physicians who throw that term at each other (and especially at patients) need to stop it. Very few things in medicine (especially true for primary prevention) are that cut and dried. And please don't any physician use the term "statin denier" in regard to a patient. Ever since the pandemic, when medicine divided down political party lines, this has become a thing. Patient autonomy reigns supreme - whatever decision a patient makes for themselves is the correct one. Physicians don't need to take affront if they decide contrary to what is recommended. This clearly supports that. And, yes, statins should be OTC.
After spending nearly 5 decades perusing information regarding the connection between nutrient intake and health outcomes, I'm reasonably certain that chronic excessive intakes of linoleic acid and arachidonic acid are major the underlying cause of heart diseases and cancers. Excerpt: "The Mediterranean diet is low in arachidonic acid and rich in healthy fats such as monounsaturated fats found in extra-virgin olive oil (EVOO), nuts and omega-3 fatty acids from fish, which has been shown to lower the risk of inflammation, heart disease, cancer, diabetes and obesity, and other degenerative diseases." (web search - Steve Blechman New red meat study)
Epidemiologists can tell that a plant-based diet reduces risk of chronic inflammatory diseases but they cannot explain why. Here's a clue: "The degree of fatty acid unsaturation of mitochondrial membrane lipids has been found to be one of those biochemical parameters that are most strongly correlated with longevity, when different species of mammals and birds are compared, with a low degree of fatty unsaturation being correlated with less lipid peroxidation and a longer normal life-span." (web search - Anna Haug Individual Variation)
Roughly 2400 years ago Plato compared rural and urban lifestyles. Comment on rural living: They will feed on barley-meal and flour of wheat, baking and kneading them, making noble cakes and loaves... they must have a relish-salt, and olives, and cheese, and they will boil roots and herbs such as country people prepare; for a dessert we shall give them figs, and peas, and beans; and they will roast myrtle-berries and acorns at the fire, drinking in moderation. And with such a diet they may be expected to live in peace and health to a good old age, and bequeath a similar life to their children after them."
Urban lifestyle: Plato mentioned "confectioners and cooks; and swineherds"...and "animals of many other kinds, if people eat them...And living in this way we shall have much greater need of physicians than before."
So, to avoid gradually accumulating arachidonic acid in adipose tissue, (the only reliable indicator of long term exposure), it is a good idea to limit intake of animal products, other than dairy, to a few meals a week.
Note also this warning from Proverbs 20:23, Be not among drunkards or among gluttonous eaters of meat, for the drunkard and the glutton will come to poverty, and slumber will clothe them with rags."
Then, there's this ancient warning in Proverbs 23: "1 When you sit down to dine with a ruler, Consider carefully what is before you, 2 And put a knife to your throat If you are a man of great appetite. 3 Do not desire his delicacies, For it is deceptive food."
Let the patient decide with all above material facts (presented in probabilistic benefit and certain cumulative harms or costs) like "informed consent" + known unknown of whether patient will ever benefit from "treating" an illness that may never happen
Fantastic topic.
Even as a religious adherent to EBM, this is the inherent limitation. You get a hypothetical blockbuster treatment that reduces all cause mortality by 10% (ARR), with an NNT of 10…and it’s an obvious no brainer….but no patient lives 10 % longer. 1 lucky patient lives….and the other 9 undertook the intervention for nothing…and we have no way of knowing who is in which camp.
So it’s no surprise that in primary prevention…even when the average effect is one that merits adoption, the vast majority of people will end up gaining nothing, and the entirety of dichotomous effect/benefit will accrue to the lucky few.
It’s yet another reminder that we must remain humble in the face of how little we know. The Rumsfeld-Ian known unknowns.
I find these 'minimal improvements' arguments very unconvincing. Firstly I suspect that the "Cohen's kappa' of such interventions is relatively high- Cohen's kappa measuring improvement divided by how much improvement can be achieved. So a therapy that turns a 1-10,000 chance into a 1-1,000,000 would have a good kappa. I think that kappa is a good measurement.
Another point is that if there are numerous drugs that have small improvements in life expectancy, than together they provide good protection. Remember that numbers less than one raised to powers go to zero rather quickly !
A third point is a pov that I may have heard first in a much earlier post on this forum (or perhaps by Prasad), which is that as long as the treatments are benign and not expensive- why not ? My statin costs me zero dollars on a drug plan that costs me nothing. So why not take it ?
Finally, abstractly one in ninety doesn't sound like a lot, but if you are on a crowded bus and you are told that someone on that bus will die today, I think you will find it unnverving !
So let me ask John a very practical question. You have a patient in say the 60-70 year range with no cardiac signs or symptoms of any sort but a mildly elevated LDL with other markers basically normal ( total cholesterol, hdl, possibly Apo A and apoB, and an age appropriate coronary calcium CT score). At what point do you advise taking a statin especially if you know that say 12.5 mg Crestor every other day will lower the patient's ldl significantly. Is taking a statin at that point equivalent to house insurance or are the adverse risks still significant. That’s really the rub of the matter because it seem to me that we really don't know what an acceptable upper level for LDL is, and one therefore has to balance the potential benefits with the potential risks which presumably can vary quite a lot from patient to patient. In other words, EBM and RCT and NNT values are all very well but they apply to populations and not to an individual (as you rightly point out).
The other issue to consider is the harms of the intervention in terms of adverse events which may not be pleasant. Statins clearly are associated with adverse events. Taking vitamin C (nothing to do with cardiac disease prevention), on the other hand, when not taken in excessive doses has literally no adverse events. Same with many other supplements. So if somebody claims that vitamin C reduces the incidence of cardiac events you'd have nothing to lose by taking vitamin C. But the same is not necessarily true of statins. In other words, one might be better off just taking bergamot juice or extract to reduce LDL levels (and trials have shown modest, up to 20% reductions) rather than statins which clearly reduce cholesterol and LDL levls far more effectively but come with potential adverse effects.
This is my hypothesis. Those that don't eat a healthy diet , don't exercise, smoke and drink to much get great benefits from statins. Their markers are high BP (24 hour> 140/90) blood sugar (A1c> 6.5), cholesterol is less important. Those who are metabolic strong may be harm by statins: risk of diabetes, muscle loss and fall in GLP. We need better screening to determine those few who benefit from statins. (full disclosure, I take a low dose of statin to hedge against the chance that I am wrong). By the way Reaven's great observational study of 2021 is evidence for my hypothesis.
1 As DR Aseem Malhotra says after doing research of the industry research data , that lower LDL in people over 60 - the higher the all cause mortality . This negates the premise that treatment lowering LDL over time will improve health outcomes.
2 As already mentioned you have to look at NNH - harms and side effects together with NNT. The author Dr Mandrola in the comments says that Statin harms are very small. I disagree .
If side effects are negligible, why are so many reported in the statin patient leaflet?
If side effects are negligible, why do so many people stop taking statins?
If side effects are negligible, why does the NNH report two serious side effects – diabetes and muscle damage – as likely occurring in 1 in 50 and 1 in 10 people respectively. New research shows how statins reduce GLP-1 by more than 50% , also lower LDL has an Alzheimer risk.
If side effects are negligible, why does Professor Rory Collins (one of the major proponents of statins) co-own a patent for a genetic marker that identifies patients at increased risk of myopathy (muscular pain)? As reported in the Sunday Times: “The test, branded as Statin–Smart, is sold online for $99 (£76) on a website that claims 29% of statin users will suffer muscle pain, weakness or cramps. The marketing material also claims that 58% of patients on statins stop taking them within a year, mostly because of muscle pain”
3 We know how bad epidemiological and cholesterol research is , besides the conflict of interests and how medicine and research is being incentivized to deliver pre -ordered results.
Great piece, love the way that you laid out the explanation. A few comments:
--- I agree that care is needed when using misinformation/disinformation terms. However, the source and context around "the number" matters. If the clear goal is to get people who are likely beneficiaries to discontinue or not initiate statin therapy by deliberately biasing what you prevent, you've got a good case for disinformation
--- As we learn, we can revise guidelines for use of a therapy. Clinical trials usually don't have many subgroup analyses and aren't powered for them but additional data will be coming. Revised U S guidelines for statin therapy rule out or reduce the number recommended for statins given better risk stratification. No one is arguing to put them in the water anymore
--- I'm ex-Pharma and, yes, pharma wants to maximize profit. They want to have more patients on therapy longer to do this. However, they also need to get their drug approved and show that it works (hopefully really well). If I have poor patient selection criteria for my clinical trial, I may fail to show that my drug works. The first 2 anti-PD1 checkpoint inhibitors for cancer approached PD-1 expression differently for patient inclusion in trials which gave 1 of them a large competitive advantage
--- Expanding on the last point, personalized medicine is a goal, knowing the best treatment for you using genetic markers and other factors to maximize efficacy and limit risk
Appreciate this analysis. The bigger question, I think, is are these people patients? The reason insurance and flying are not apt comparisons is because those are transactions between a buyer and seller. Think about oncology. They frequently celebrate trials for terrible diseases that extend life weeks to months - these are breakthroughs! The cost per patient for treatment (idk exact numbers) is far greater than a statin. Yet we don’t have this conversation, because everyone agrees that those are patients in desperate need of help - and hope. Is an individual with high LDL and no other risk factors a patient with a disease? If so then all of this is critical and relevant, and I favor your interpretation of decision making. But if this is really just wellness disguised as medicine - then we either should make statins OTC or more seriously consider the value as specialists. With the pervasiveness of CAC scores and lipid panels I have not decided where I land on this question.
"They frequently celebrate trials for terrible diseases that extend life weeks to months - these are breakthroughs!"
It was probably around 1976 when my physician father (Family Practice) told me oncologists get really excited when a treatment extends a patient's life by one month. Even at age 20, I thought, "By that time, the cancer patient is really sick, and probably in considerable pain. Is there really a great net benefit for the patient in continuing to live another month? But there IS for the medical providers.
By the way, 44 years later, when my father was 91 and dying in the hospital, he had to STARVE HIMSELF TO DEATH to get around the hospital's overactive (and profitable) life extension procedures.
Cholesterol is not the cause of heart attacks. They are markers indicating inflammation. This is how Big Pharma has deceived the medical community for their profits. That is like saying the cause of house fires are the firemen. Yes firemen arrive at all fires, but they did not cause the fire. Statins are Implicated in muscle cramps, brain fog, and diabetes. They may also contribute greatly to Alzheimer's, The brain needs cholesterol to function. An independent (non-Big Pharma) study of 1 million people taking statins for 5 years, compared to 1 million not taking Statins showed the statin group lived 3 days longer. Big Pharma touts a RELATIVE decrease in heart attacks of 29 %, but the ACTUAL decrease is only 1%. That is bogus science. Also in 1985 normal cholesterol levels were 300. Statins came out in 1986 and the next year normal levels were arbitrarily decreased to 200 (I wonder why?) Statins are Big Pharma's number one drug ($20 Billion per year).
This is a huge problem in gender medicine in the US, where claims that questions regarding studies and statements about the weak certainty of evidence are "misinformation" or political. E.g., "Combating Scientific Disinformation on Gender-Affirming Care" in NEJM.
There are surely political actors and misinformation in the field, but also a lot of physicians and researchers doing due diligence and finding serious concerns regarding current practice vs medical best practice. Thus in Europe one has instead: "ESCAP statement on the care for children and adolescents with gender dysphoria: an urgent need for safeguarding clinical, scientific, and ethical standards " (ESCAP is an umbrella organization of child and adolescent psychiatry societies from over 30 European countries, https://pubmed.ncbi.nlm.nih.gov/38678135/ )
At least the American Society of Plastic Surgeons has done due diligence and looked at the evidence: "Position Statement on Gender Surgery for Children and Adolescents"--https://www.plasticsurgery.org/documents/health-policy/positions/2026-gender-surgery-children-adolescents.pdf
The evidence is similarly low and very low certainty for the other medical gender interventions for under 19 (and in some systematic reviews which go up to age 26).
Hoping the US journals and other US medical societies start following the evidence soon for this topic. It is already going to be hard for them to explain why they waited so long, to those who have (rightfully, in this topic!) lost trust in them.
I may be misunderstanding the meaning of such a skewed distribution, but doesn't the fact that 93% of men and 97% of women only have harms and no gains suggest that we don't understand well enough why/how the preventive therapy works--the mechanism, for whom it's appropriate, etc.? Isn't this a good argument for treating the problem when it appears and not ahead of time?
Excellent common-sensical explanation why preventive medicine is a myth.
As a layman, I find this observation striking. What about those 7% of men and 3% of women is different from the others? This is where the car insurance analogy fails. As a driver, one can do everything the right way and still be involved in a collision because something out of one's control went wrong that day. For the statin situation, something about you, some prior condition or set of conditions, exist that lead you to an event but that statins seem to ameliorate. What is that prior condition or set of conditions?
Excellent! Well said. And now you should follow it with a NNT discussion that explains further. For instance, even if you isolate those who experience the anti-hypertensive benefit, 93% see no benefit—only harms and costs. Worth it? Interesting discussion. To me, the London Tube survey comparisons are fascinating, but maybe misleading, because there is no 'certainty' of gaining a short amount of time with any preventive treatment. How about if the survey was truer to primary prevention statin data for most people (risks <20% at 10 years). That would be a 0% chance of gaining one year versus a 0% chance of gaining more than that. Tough call? This is because only EXTRAPOLATIONS beyond trial durations 'find' any mortality benefit (and they may be wrong). For secondary prevention, best case scenario, it's a 1.2% chance of being in the group that sees a long term mortality benefit (possibly lasting 5-10 years) and it comes with a 2% chance of getting diabetes (a forever gift) plus all other harms and costs. Worth it? 99% chance no benefit? Tricky.
I'm surprised to see Dr. Mandrola using mathematical modelling as an argument against systematic review of clinical trials. It's Imperial College, for God's sake! With their track record, I wouldn't take their calculations as an argument to support anything.
Here is my argument. If the statin makers saw a chance that longer term statin taking improves the OS, they would make the trials longer. They would have an excellent argument for more sales. But they never did. So for me, any claim for better results on longer statin use is just a speculation. Unfounded speculation.
The study in BMJ Open actually shows the prolongation of life from - 10 to + 27 days. Median + 3 days for primary and + 4 days for secondary prevention.
I don't think you can exactly paint or tar Imperial College with a single brush after the good Dr. Neil Fergusson from Imperial managed to predict (willfully some might say) the impact of every epidemic/pandemic he has looked at completely wrong (not just Covid but also Mad Cow Disease and other infectious diseases). But people in other departments, such as cardiology, might be a lot more reliable and circumspect than Ferguson. Every instution has some bad players in it.
Perhaps there are better people around there. But they should speak up when Ferguson destroys reputation of the institution. It's always Imperial College with outrageous prediction. It's always helping to increase panic.
You do realize that Imperial College is just as big as Harvard or MIT. and Ferguson didn't destroy the reputation of Imperial. Ferguson destroyed his own reputation.
I know it's not fair. But I only hear about imperial college when a new epidemy starts and journalists are looking for a really juicy prediction how many people will die this time. And they are never disappointed, it's always a number for the front page. I'm aware that a reasonable number would probably get lost and that I might not hear about reasonable predictions from other IC departments. But that's where we are.