This is all assuming that lowering cholesterol actually reduces heart attacks. As I understand it, having looked at some of the studies myself, it really only helps men over a certain age who have already had a heart attack, and even then the benefit is very slight.
Several years ago I fell ill in mid Autumn. I say “ill” because I developed all the nasty symptoms of fever including joint and muscle aches and a general lethargy – without actually having an elevated temperature. About three months into this, having been told by my PCP that it was likely a virus and that I should just wait for it to clear, I decided to investigate myself. I looked at all aspects of my life that might have been different enough to precipitate this illness. Among my various considerations was a new medication I’d started not long before this started. At that time, I simply did what my doctor suggested. After all, he knows best. I decided to quit that atorvastatin for a while just to see. Less than ten days later the “illness” lifted. To be certain, I waited a week longer and, still feeling fine, decided to re-challenge myself with atorvastatin. In less than a week I had my “fever” and “illness” back.
Now, you can tell me that my initially quitting the statin set me up for The Placebo Effect and that re-challenging myself set me up for The Nocebo Effect. OK. But you’ll not be able to tell me definitively that my initial “illness” was caused by Nocebo. I’d been innocently naive of side effect reporting at that time. I’m much more circumspect across the board now. Yes, ripe for all sorts of ‘cebos – with my eyes open.
Randomized Controlled Trials can tell researchers a great deal about the group-in-general that they have singled out for researching. They are not necessarily decisively informative concerning the unique issue(s) of any particular individual.
Having done further research and seeing that, for my niche, the absolute risk reduction is between 1% and 2%, and considering my “illness”, I forego any statins. Further, I forego other forms of cholesterol reduction.
John, Instead of measuring subjective side effects of statins has anyone measured markers of muscle damage? If those patients who cannot tolerate statins show more consistent indications of muscle damage, then it seems there is a proper pathophysiologic basis for statin intolerance.
I imagine there will be some pts where bempedoic acid will be required (+/- actually necessary). Those people are currently likely on ezetimibe. So I think at best it will be an add on drug, esp given it will likely be much more expensive than ezetrol.
I don’t mind that this becomes available. Even though statin “intolerance” rarely seems “real”, it feels real enough to pts, and if they refuse statin, there’s not much you can do.
I am toying with the idea of reproducing the trial procedure….of having pt to acknowledge in writing that they are foregoing a drug with greater benefit, in order to take a med with less.
Hello, I am deeply shaken by this post. It has been established that statins have close to no effect for primary prevention (vast majority of thise who are prescribed statins,) and a modest one in secondary prevention. The effect is due to anti-inflammatory action and not lowering of cholesterol, (the effect is observable before cholesterol goes down). Also, for the cholesterol hypothesis to work, multiple ad hoc side hypothesis are necessary which does not reflect well on the central one !!! Very bad science indeed...Dr Malcolm Kendricks has proposed a simple and biologically plausible mechanism that can explain why rate of hearth disease goes up in various diseases and contexts that do not have any connexion between them . He has a blog and has published many books, namely The plot tickens. He has a very deep knowledge and respect of the scientific method. It's a must and fun read for every cardiologist.
Nice article. What amazes me is that in all the articles on drugs and conditions, diet is rarely ever mentioned, and when it is, it's usually almost completely devoid of any studies or stats. The SAD (
Standard American Diet) is terrible. Full Stop. Eat that way and your chance of disease and a serious decline in life quality almost inevitably follow. Where is my "evidence"? --mainly watching people grow old and die for the last 76 years. Ive beaten back some deadly conditions with diet personally. Eating clean, fasting, very low fat diet, etc. have been known for a very long time all over the world to be far superior to snake oil, pharmaceuticals, and now the crap food commonly produced and marketed.
Do I think pharmaceuticals or allopathic medicine are useless? Not at all. My grandfather and father and several cousins were pharmacists, and I know at least my dad knew his stuff well. I'm probably alive today due to allopathic treatment and some limited drugs. But for a better outcome overall, diet must be considered.
My mother got off statins after she ended up with an issue with one of her eyes. Not convinced she needed them in the first place - her numbers were borderline. Is it possible that people get off statins when they realize that they didn't actually need the prescription in the first place and it's not worth the risk especially when they end up on additional meds that they really do need?
Psychosomatic effects could also be taken seriously rather than written off. Patients attach real value to not taking medication, especially if it's a lifetime prescription.
Edit: That SAMSON study had like 60 people, yet through statistics voodoo the authors extract tiny confidence intervals of a few percent for some measures. I propose that correlations were swept under the rug and the true uncertainties are much larger. Correct me if I'm wrong (my reading skills are modest), but it looks like each month of statin/placebo/nothing is treated as an independent test for the Howard et al. figure. Yet, patients with true statin side effects would experience correlation between and within statin months. Where do the confidence intervals come from?
Edit #2: Look at patient 43 on page 8 of the Supplementary Appendix. Four statin periods with quickly growing ill effects every time. Where is the equivalent placebo effect? If I were that patient, I would be totally peeved about the study conclusions.
Besides that, the placebo effect may reflect prior experience that statins cause misery. Existence of a strong placebo effect does not imply that statins cause no problems. It's like classical conditioning with punishment.
The study abstract is also wrong to claim "Stopping was no more frequent for statin than placebo (P = 0.173)". In fact stopping was more frequent for statin, even if statistical significance was not reached.
Your review matches my clinical experience since statins first introduced. One point, Pharma reps showing up in our offices with free lunches and "talking points." Please stop. Lunch isn't free and talking points are about sales not science whether from the rep or the paid "thought leader," the goal to influence prescribing habits not educate. EBM.
As a practicing Cardiologist I am amazed at the difference between the number of my patients that claim to have statin intolerance and what is actually seen in clinical trials. Even if most of it is a nocebo effect it is very difficult to get patients to stay on their statins if they’re convinced they’re having side effects. There is also a tremendous amount of anti-statin misinformation online, which is put out by the alternative medicine industry, trying to get patients to take ineffective supplements to lower the cholesterol. It’s not unusual for a new patient to come to the office for a consultation and one of the first things they communicate to me is no matter what they will not take a statin. I welcome Bempedoic acid as an alternative but so far most of my patients don’t want to take it because it is very expensive and has not generally been covered by insurance but perhaps with this new trial that will change.
I've been an RN for 40 years, bedside to management, still work full time at a healthy 70 yrs old. I started on Lipitor 10 yrs ago and my liver just went nuts. No muscle pain, but routine labs done for another reason showed really concerning liver function. Good bye Lipitor, started PSK9 and Ezetimibe, and my lipid panels are now the envy of my doctors... Just as an aside, looks like I have a familial hypercholesterolemia, not figured out until my mother moved near me as she got older and went to the same cardiologist. No heart attack history in my family, my numbers were previously attributed to needing to eat a different diet/exercise more/modify stress/etc etc over the years which I could not convince male PCP's I actually WAS doing.
Even assuming someone has statin intolerance on one statin, shouldn’t they first try at least two other statins plus other dosing schedules before giving up on statins? Ezetimibe is available as a generic so I don’t know why you would take it as a combo pill with BA 🤔. There are also PCSK9 inhibitors for those who can meet the insurance requirements to get one and they seem to have a good side effect profile. Anyway I’m puzzled/bemused by this story line of finally having a drug for statin intolerance when we already had some options.
I'm a career medical writer who specialized in cardiology CME produced by Big Pharma. When my cardiologist put me on Crestor, I developed miserable, weird muscle pains all over my body unlike anything I'd ever felt. I can be a somatizer (it's an occupational hazard with any topic except male urology), but this sure was miserable, and kept me from exercising. It wasn't much better on (cheaper) generic simvastatin 20 mg, so I switched myself to alternate-day dosing based on an obscure trial out of India. Aha! No more muscle pain. After some months I went back to 20 mg/day, no problem. And now I'm up to 40. So: start low, go slow, and be willing to switch agents! Even if muscle pain is in fact "nocebo," it still hurts!
N.B. My doc is a paid speaker for Crestor (I call him the "Crest-Whore" to his face). He says he likes the mortality data vs other agents. I'm willing to try it again--at the lowest dose, on alternate days.
Fair point that it’s approval will lead to needless $$$.
On the other hand, the path to something being cheap and generic requires that it go thru a brand name phase. So it is. Will be better to have this tool in the arsenal down the road.
Also it may be nocebo butttt also nocebo is a real experiential thing like all functional neurological disorders. And it’s not realistic to expect you can get everyone on board that it’s basically a psychogenic response.
I personally find that KM curve pretty exciting, especially when you’re working with a chronic process and we’re seeing outcomes at only 40 weeks.
Olive leaf, high potency cayenne tincture, nattokanise, hawthorn berry and vitamin D work just as well for heart distress. But then you are cutting big pharma out of the process and no cardiologist has the balls to buck them.
This is all assuming that lowering cholesterol actually reduces heart attacks. As I understand it, having looked at some of the studies myself, it really only helps men over a certain age who have already had a heart attack, and even then the benefit is very slight.
Several years ago I fell ill in mid Autumn. I say “ill” because I developed all the nasty symptoms of fever including joint and muscle aches and a general lethargy – without actually having an elevated temperature. About three months into this, having been told by my PCP that it was likely a virus and that I should just wait for it to clear, I decided to investigate myself. I looked at all aspects of my life that might have been different enough to precipitate this illness. Among my various considerations was a new medication I’d started not long before this started. At that time, I simply did what my doctor suggested. After all, he knows best. I decided to quit that atorvastatin for a while just to see. Less than ten days later the “illness” lifted. To be certain, I waited a week longer and, still feeling fine, decided to re-challenge myself with atorvastatin. In less than a week I had my “fever” and “illness” back.
Now, you can tell me that my initially quitting the statin set me up for The Placebo Effect and that re-challenging myself set me up for The Nocebo Effect. OK. But you’ll not be able to tell me definitively that my initial “illness” was caused by Nocebo. I’d been innocently naive of side effect reporting at that time. I’m much more circumspect across the board now. Yes, ripe for all sorts of ‘cebos – with my eyes open.
https://www.mayoclinic.org/diseases-conditions/high-blood-cholesterol/expert-answers/rhabdomyolysis/faq-20057817
Randomized Controlled Trials can tell researchers a great deal about the group-in-general that they have singled out for researching. They are not necessarily decisively informative concerning the unique issue(s) of any particular individual.
Having done further research and seeing that, for my niche, the absolute risk reduction is between 1% and 2%, and considering my “illness”, I forego any statins. Further, I forego other forms of cholesterol reduction.
Try looking at it with different perspective
BA + HIS + EZE together can give as much reduction at lesser cost ( sp in India) than the hyped PCSK9i
So why not promote this combine in statin tolerant patients
John, Instead of measuring subjective side effects of statins has anyone measured markers of muscle damage? If those patients who cannot tolerate statins show more consistent indications of muscle damage, then it seems there is a proper pathophysiologic basis for statin intolerance.
I imagine there will be some pts where bempedoic acid will be required (+/- actually necessary). Those people are currently likely on ezetimibe. So I think at best it will be an add on drug, esp given it will likely be much more expensive than ezetrol.
I don’t mind that this becomes available. Even though statin “intolerance” rarely seems “real”, it feels real enough to pts, and if they refuse statin, there’s not much you can do.
I am toying with the idea of reproducing the trial procedure….of having pt to acknowledge in writing that they are foregoing a drug with greater benefit, in order to take a med with less.
Hello, I am deeply shaken by this post. It has been established that statins have close to no effect for primary prevention (vast majority of thise who are prescribed statins,) and a modest one in secondary prevention. The effect is due to anti-inflammatory action and not lowering of cholesterol, (the effect is observable before cholesterol goes down). Also, for the cholesterol hypothesis to work, multiple ad hoc side hypothesis are necessary which does not reflect well on the central one !!! Very bad science indeed...Dr Malcolm Kendricks has proposed a simple and biologically plausible mechanism that can explain why rate of hearth disease goes up in various diseases and contexts that do not have any connexion between them . He has a blog and has published many books, namely The plot tickens. He has a very deep knowledge and respect of the scientific method. It's a must and fun read for every cardiologist.
Nice article. What amazes me is that in all the articles on drugs and conditions, diet is rarely ever mentioned, and when it is, it's usually almost completely devoid of any studies or stats. The SAD (
Standard American Diet) is terrible. Full Stop. Eat that way and your chance of disease and a serious decline in life quality almost inevitably follow. Where is my "evidence"? --mainly watching people grow old and die for the last 76 years. Ive beaten back some deadly conditions with diet personally. Eating clean, fasting, very low fat diet, etc. have been known for a very long time all over the world to be far superior to snake oil, pharmaceuticals, and now the crap food commonly produced and marketed.
Do I think pharmaceuticals or allopathic medicine are useless? Not at all. My grandfather and father and several cousins were pharmacists, and I know at least my dad knew his stuff well. I'm probably alive today due to allopathic treatment and some limited drugs. But for a better outcome overall, diet must be considered.
My mother got off statins after she ended up with an issue with one of her eyes. Not convinced she needed them in the first place - her numbers were borderline. Is it possible that people get off statins when they realize that they didn't actually need the prescription in the first place and it's not worth the risk especially when they end up on additional meds that they really do need?
Psychosomatic effects could also be taken seriously rather than written off. Patients attach real value to not taking medication, especially if it's a lifetime prescription.
Edit: That SAMSON study had like 60 people, yet through statistics voodoo the authors extract tiny confidence intervals of a few percent for some measures. I propose that correlations were swept under the rug and the true uncertainties are much larger. Correct me if I'm wrong (my reading skills are modest), but it looks like each month of statin/placebo/nothing is treated as an independent test for the Howard et al. figure. Yet, patients with true statin side effects would experience correlation between and within statin months. Where do the confidence intervals come from?
Edit #2: Look at patient 43 on page 8 of the Supplementary Appendix. Four statin periods with quickly growing ill effects every time. Where is the equivalent placebo effect? If I were that patient, I would be totally peeved about the study conclusions.
Besides that, the placebo effect may reflect prior experience that statins cause misery. Existence of a strong placebo effect does not imply that statins cause no problems. It's like classical conditioning with punishment.
The study abstract is also wrong to claim "Stopping was no more frequent for statin than placebo (P = 0.173)". In fact stopping was more frequent for statin, even if statistical significance was not reached.
Your review matches my clinical experience since statins first introduced. One point, Pharma reps showing up in our offices with free lunches and "talking points." Please stop. Lunch isn't free and talking points are about sales not science whether from the rep or the paid "thought leader," the goal to influence prescribing habits not educate. EBM.
As a practicing Cardiologist I am amazed at the difference between the number of my patients that claim to have statin intolerance and what is actually seen in clinical trials. Even if most of it is a nocebo effect it is very difficult to get patients to stay on their statins if they’re convinced they’re having side effects. There is also a tremendous amount of anti-statin misinformation online, which is put out by the alternative medicine industry, trying to get patients to take ineffective supplements to lower the cholesterol. It’s not unusual for a new patient to come to the office for a consultation and one of the first things they communicate to me is no matter what they will not take a statin. I welcome Bempedoic acid as an alternative but so far most of my patients don’t want to take it because it is very expensive and has not generally been covered by insurance but perhaps with this new trial that will change.
I've been an RN for 40 years, bedside to management, still work full time at a healthy 70 yrs old. I started on Lipitor 10 yrs ago and my liver just went nuts. No muscle pain, but routine labs done for another reason showed really concerning liver function. Good bye Lipitor, started PSK9 and Ezetimibe, and my lipid panels are now the envy of my doctors... Just as an aside, looks like I have a familial hypercholesterolemia, not figured out until my mother moved near me as she got older and went to the same cardiologist. No heart attack history in my family, my numbers were previously attributed to needing to eat a different diet/exercise more/modify stress/etc etc over the years which I could not convince male PCP's I actually WAS doing.
Even assuming someone has statin intolerance on one statin, shouldn’t they first try at least two other statins plus other dosing schedules before giving up on statins? Ezetimibe is available as a generic so I don’t know why you would take it as a combo pill with BA 🤔. There are also PCSK9 inhibitors for those who can meet the insurance requirements to get one and they seem to have a good side effect profile. Anyway I’m puzzled/bemused by this story line of finally having a drug for statin intolerance when we already had some options.
I'm a career medical writer who specialized in cardiology CME produced by Big Pharma. When my cardiologist put me on Crestor, I developed miserable, weird muscle pains all over my body unlike anything I'd ever felt. I can be a somatizer (it's an occupational hazard with any topic except male urology), but this sure was miserable, and kept me from exercising. It wasn't much better on (cheaper) generic simvastatin 20 mg, so I switched myself to alternate-day dosing based on an obscure trial out of India. Aha! No more muscle pain. After some months I went back to 20 mg/day, no problem. And now I'm up to 40. So: start low, go slow, and be willing to switch agents! Even if muscle pain is in fact "nocebo," it still hurts!
N.B. My doc is a paid speaker for Crestor (I call him the "Crest-Whore" to his face). He says he likes the mortality data vs other agents. I'm willing to try it again--at the lowest dose, on alternate days.
Fair point that it’s approval will lead to needless $$$.
On the other hand, the path to something being cheap and generic requires that it go thru a brand name phase. So it is. Will be better to have this tool in the arsenal down the road.
Also it may be nocebo butttt also nocebo is a real experiential thing like all functional neurological disorders. And it’s not realistic to expect you can get everyone on board that it’s basically a psychogenic response.
I personally find that KM curve pretty exciting, especially when you’re working with a chronic process and we’re seeing outcomes at only 40 weeks.
Olive leaf, high potency cayenne tincture, nattokanise, hawthorn berry and vitamin D work just as well for heart distress. But then you are cutting big pharma out of the process and no cardiologist has the balls to buck them.