Not a fan of statins. Went through all of them and had severe muscle pain each time. For me, the only cholesterol drug without side effects is Praluent.
I'm sorry you didn't have the best experience with them! They're not for everyone (though I maintain the opinion that people should have the right to try them OTC). PCSK9is are awesome - and seem to have even less side effects. If they were generic & easier to administer, I would have advocated for them in the piece in a heartbeat in place of statins! (no pun intended)
Thanks for understanding. I have similar problems to other families of drugs (i.e., antihypertensive, diabetes). I'm coming to terms with the fact that I will most likely die from something that could have been treated with simple drugs that I cannot tolerate.
A pigouvian tax* on added sugars and pigouvian subsidy* for fiber in foods and beverages would probably accomplish orders of magnitude more for public health. But people would be mad, and this administration would never do it.
* not in the sense of classical externalities, but in the sense of people's hyperbolic-discounting, marshmellow-test-failing monkey brains making decisions that impose costs on their future selves who effectively didn't get to participate in the decision.
Hey Brian - great questions, thanks for prodding! FWICT the clearest and most consistent evidence shows that statins primarily reduce cardiovascular events — and that’s where their biggest benefit lies (IMO we’ll get a much clearer picture of statins’ true preventive value beyond MACE when STAREE and PREVENTABLE deliver their final readouts. Both are designed to answer exactly this question with high-quality prospective data).
Mechanistically, it tracks: LDL-rich plaque → inflammation → rupture → clot → heart attack or stroke. Inhibit HMG-CoA reductase, drop LDL, and you interrupt that cascade. As I mentioned in the piece, the 2010 CTT meta-analysis of statins in prospective RCTs (~170,000 patients) found ~20% fewer major vascular events per 1 mmol/L LDL reduction.
If I'm thinking of the studies you're recollecting: claims that high LDL is protective usually come from retrospective datasets riddled with survivor bias - the same statistical trap that once made metformin look like an anti-aging miracle.
For a great breakdown of the cholesterol debate, I recommend checking out Thomas Dayspring’s podcast appearances. He’s a world-class lipidologist with a gift for cutting through noise (and adding a few laughs along the way, he's pretty funny).
Survivorship bias is indeed a significant problem in studies suggesting protective effects of LDL on all-cause mortality, particularly those conducted in older populations. This bias rarely acts in isolation. It is linked with other methodological challenges. Most notably linked with reverse causality, where low LDL-C often serves as a marker of underlying and severe illness. There can also be confounding by factors such as lipid-lowering treatment.
Regarding reverse causality, for example, conditions such as cancer, malnutrition, and chronic infection can all lower LDL levels.
ChatGPT tells me you would need to treat 250 moderate to high risk individuals for 5 years to prevent one all cause mortality. The annual cost for taking it otc would be about $50. So that's 250*5*$50 = $62500 per life saved. Let's round it off to $10k per QUALY. It's not malaria nets but in the US context it's orders of magnitude more efficient than most of our other healthcare spending.
ChatGPT verbatim:
"Primary Prevention (Individuals Without Established Cardiovascular Disease)
Low-Risk Individuals: For those with a 10-year cardiovascular risk below 10%, studies have shown no statistically significant mortality benefit from statin therapy. The Cholesterol Treatment Trialists' (CTT) meta-analysis, encompassing over 130,000 patients, found no significant reduction in all-cause mortality for these low-risk groups.
Moderate to High-Risk Individuals: In populations with higher baseline cardiovascular risk, statins have demonstrated a modest mortality benefit. For example, the U.S. Preventive Services Task Force (USPSTF) analysis reported a 0.4% absolute reduction in all-cause mortality over approximately 5 years, translating to an NNT of 250. "
I agree 100% with this thesis - statins should be OTC, with minimal restrictions.
Right now, preventative measures for atherosclerosis aren't implemented until there is a reading of high blood pressure or a signal on a coronary artery calcification scan, usually when people are older than 50.
But we know now from autopsy studies etc that atherosclerosis begins in childhood years in about 20% of individuals. Autopsy scans show fatty streaks - the earliest stage in such individuals. For that subset, it's critical to start interventions as early as possible. And we know that dietary and lifestyle interventions aren't super effective for most people.
To find those individuals, we should be able to use genetics. A cheap, quick ultrasound of the carotid artery could also be helpful.
Regarding red yeast rice extract - I think it would be better to just cite Wikipedia as a source (https://en.wikipedia.org/wiki/Red_yeast_rice#U.S._regulatory_restrictions) -- your reference doesn't actually back up the claim - it's about further crackdowns on the addition of additional statin molecules (adulteration). What you say is correct though - the FDA has been cracking down on it since it contains a statin molecule.
Not a fan of statins. Went through all of them and had severe muscle pain each time. For me, the only cholesterol drug without side effects is Praluent.
I'm sorry you didn't have the best experience with them! They're not for everyone (though I maintain the opinion that people should have the right to try them OTC). PCSK9is are awesome - and seem to have even less side effects. If they were generic & easier to administer, I would have advocated for them in the piece in a heartbeat in place of statins! (no pun intended)
Thanks for understanding. I have similar problems to other families of drugs (i.e., antihypertensive, diabetes). I'm coming to terms with the fact that I will most likely die from something that could have been treated with simple drugs that I cannot tolerate.
A pigouvian tax* on added sugars and pigouvian subsidy* for fiber in foods and beverages would probably accomplish orders of magnitude more for public health. But people would be mad, and this administration would never do it.
* not in the sense of classical externalities, but in the sense of people's hyperbolic-discounting, marshmellow-test-failing monkey brains making decisions that impose costs on their future selves who effectively didn't get to participate in the decision.
Why don’t you do all cause mortality rather than cardiovascular events? Data I have seen seems to suggest high LDL has protective effects
Hey Brian - great questions, thanks for prodding! FWICT the clearest and most consistent evidence shows that statins primarily reduce cardiovascular events — and that’s where their biggest benefit lies (IMO we’ll get a much clearer picture of statins’ true preventive value beyond MACE when STAREE and PREVENTABLE deliver their final readouts. Both are designed to answer exactly this question with high-quality prospective data).
Mechanistically, it tracks: LDL-rich plaque → inflammation → rupture → clot → heart attack or stroke. Inhibit HMG-CoA reductase, drop LDL, and you interrupt that cascade. As I mentioned in the piece, the 2010 CTT meta-analysis of statins in prospective RCTs (~170,000 patients) found ~20% fewer major vascular events per 1 mmol/L LDL reduction.
If I'm thinking of the studies you're recollecting: claims that high LDL is protective usually come from retrospective datasets riddled with survivor bias - the same statistical trap that once made metformin look like an anti-aging miracle.
For a great breakdown of the cholesterol debate, I recommend checking out Thomas Dayspring’s podcast appearances. He’s a world-class lipidologist with a gift for cutting through noise (and adding a few laughs along the way, he's pretty funny).
I was thinking something similar.
Survivorship bias is indeed a significant problem in studies suggesting protective effects of LDL on all-cause mortality, particularly those conducted in older populations. This bias rarely acts in isolation. It is linked with other methodological challenges. Most notably linked with reverse causality, where low LDL-C often serves as a marker of underlying and severe illness. There can also be confounding by factors such as lipid-lowering treatment.
Regarding reverse causality, for example, conditions such as cancer, malnutrition, and chronic infection can all lower LDL levels.
ChatGPT tells me you would need to treat 250 moderate to high risk individuals for 5 years to prevent one all cause mortality. The annual cost for taking it otc would be about $50. So that's 250*5*$50 = $62500 per life saved. Let's round it off to $10k per QUALY. It's not malaria nets but in the US context it's orders of magnitude more efficient than most of our other healthcare spending.
ChatGPT verbatim:
"Primary Prevention (Individuals Without Established Cardiovascular Disease)
Low-Risk Individuals: For those with a 10-year cardiovascular risk below 10%, studies have shown no statistically significant mortality benefit from statin therapy. The Cholesterol Treatment Trialists' (CTT) meta-analysis, encompassing over 130,000 patients, found no significant reduction in all-cause mortality for these low-risk groups.
Moderate to High-Risk Individuals: In populations with higher baseline cardiovascular risk, statins have demonstrated a modest mortality benefit. For example, the U.S. Preventive Services Task Force (USPSTF) analysis reported a 0.4% absolute reduction in all-cause mortality over approximately 5 years, translating to an NNT of 250. "
I agree 100% with this thesis - statins should be OTC, with minimal restrictions.
Right now, preventative measures for atherosclerosis aren't implemented until there is a reading of high blood pressure or a signal on a coronary artery calcification scan, usually when people are older than 50.
But we know now from autopsy studies etc that atherosclerosis begins in childhood years in about 20% of individuals. Autopsy scans show fatty streaks - the earliest stage in such individuals. For that subset, it's critical to start interventions as early as possible. And we know that dietary and lifestyle interventions aren't super effective for most people.
There is a strong case that if we could target statins (or one-time gene therapy) to high risk individual, we could prevent 90% of heart disease. Read => https://www.ahajournals.org/doi/10.1161/circulationaha.107.717033
To find those individuals, we should be able to use genetics. A cheap, quick ultrasound of the carotid artery could also be helpful.
Regarding red yeast rice extract - I think it would be better to just cite Wikipedia as a source (https://en.wikipedia.org/wiki/Red_yeast_rice#U.S._regulatory_restrictions) -- your reference doesn't actually back up the claim - it's about further crackdowns on the addition of additional statin molecules (adulteration). What you say is correct though - the FDA has been cracking down on it since it contains a statin molecule.
Where would you say a study like this falls short? It seems to have no benefit in this case:
https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/416105