I agree this study is a confusing mishmash and the authors likely spent a lot of time trying to create something significant from it.
Oddly, the reviewers (one of which is a consultant for CLEERLY, the CCTA AI) seem quite enthusiastic about it.
One critique of your critique... Your wrote: So the conclusion that “patients without CAD have no benefit from statins” goes against more than 20 trials of statin therapy as primary prevention. When you make big conclusions, you should have strong data. "
The statin trials define patients without CAD as those without clinical ASCVD, such as MI, stent, CABG. They haven't used subclinical coronary atherosclerosis which can be quite advanced in patients without clinical events.
Patients with advanced subclinical CAD are often at higher risk than those patients who have had events but are being treated optimally with medical therapy.
This trial (I presume) is using CCTA data to say that patients have no CAD.
This defines an entirely different population who truly are at a very very low risk of clinical CAD events.
Mark Twain was right. 1982. I was up all night in the seven bed CCU. Two deaths. Still in their rooms. EKG paper strewn everywhere. The rest of the people with Swan-Ganz catheter's getting IV nitroglycerin and morphine. A few got TPA as part of a study. No stents. Commonality men, 50 to 60 years of large STEMI. Fast forward 2025. How many ruptures of the ventricle, ventricular septal defects and blown papillary muscles are in the ICU every night?? Now mortality is down what 30 to 40%..Average age of admit?
Social media would make you think it was Magic, and that statins are another example of big pharma trying to steal from the population. I hope we don't go back to the future. My LDL was 200- now very low. I say thank you
As I’ve said before, where have the decent editors gone? That even a sub-journal of JACC would allow the type of conclusion language as was used with this paper, given the methodology of this paper, is gobsmacking.
Always appreciate you digging into the weeds (and supplements) of papers. It makes no sense when “any” use of X (including a very low prevalence) would exert a larger clinical effect than a higher prevalence of use. It flies in the face of the basic pharmacology principle of dose response.
Their “10% increase in use” is simply based on filled prescription days. We know nothing about dose (or even mean dosage prescribed). We know nothing about delta LDL. For all we know, this simply reflects the effect of very poor compliance with homeopathic statin doses.
All in all, this paper is a gong show that serves no purpose other than to feed the confirmation biases of those who are given to those sorts of proclivities.
I can’t imagine an instance when I would take a statin, or recommend someone else take a statin.
The odd thing is, that when you take statins, you have side effects. They are very, very common in a sizable percentage of people taking them, just an empirical guess 5 - 15%.
But when you look at the studies, side effects are very rare. There is so much bias, so much.
“Importantly, despite the small reductions in nonfatal heart attacks and strokes, statins were not associated with a reduction in serious illness overall (relative risk = 0.99; 95% confidence interval, 0.94 to 1.04).4 Adverse events from statin use include myalgia and new-onset diabetes at a rate of 4.8% (number needed to harm [NNH] = 21) and 0.49% over five years (NNH = 204), respectively.5,6 Other adverse events, although often reported, have not been well studied.”
Your link is about patients at low risk for CV disease. This is not the same as “no CAD”. For example, one could have no CAD yet be at high risk due to age, hypertension, diabetes and smoking. This person benefits from a statin to lower risk of MACE.
SAMSON enrolled only people who had reported symptoms within two weeks of starting statins, which excluded longer-term or delayed adverse effects. This design bias made the study more convenient logistically but less representative of the general population of statin users, where side effects may appear months after initiation.
Single drug and dose:
The trial tested only atorvastatin 20 mg daily, which limits generalizability. Responses might differ for other statins (e.g., simvastatin, rosuvastatin) or for higher doses often used in secondary prevention.
Short treatment periods:
Each trial phase lasted only one month. Muscle or fatigue-related side effects could develop over longer durations, meaning subacute or cumulative effects weren’t captured.
Limited sample size:
The study involved only 60 participants, which restricts statistical strength and makes it difficult to detect small differences between statin and placebo periods.
Interpretive Concerns:
The nocebo framing—though likely valid for some participants—may have encouraged overgeneralization that statin side effects are mostly psychological. Some clinicians argue that downplaying genuine
Interesting how people who have no argument simply attack me because I'm not a doctor. I'm glad I'm not a doctor. I can think for myself once in awhile, and very few doctors can.
Slow your roll with the whining, bud. Where was the attack? Merely pointing out facts.
If you don’t want a statin, that’s your choice.
You shouldn’t be recommending any treatment of anything to anybody, since you’re not a doctor. Statin, or otherwise. Assuming you actually recognize your limitations.
As always, erudite and well written, thank you. But, respectfully disagree, Dr. M. First, too much causal language: “the 10% increase in statins resulted in a 5% lower rate of events.” As you know, virtually all changes in the study are likely healthy user bias, and definitely associations. Second, I beg you to reassess statin data through the lens of true benefit. The great majority of ‘benefit’ is in ‘revascularization’, something you have rightly pointed out is not a benefit at all. At primary prevention control rates mortality—the real reason patients take the drug—is totally unchanged. Meanwhile, non-fatal MI is a false and often misleading surrogate, and statin harms are very real and virtually always omitted from such discussions. Looking forward to your next piece, but fear your statin advocacy is misled by clever CTT (i.e. industry) hand-waving.
Statistical reanalysis of this study is illuminating. Sensible Medicine is doing a fine job.
The bottom line in the current conclusions about statin use for asymptomatic patients is that most accrue a mild ARR of MACE Of 3-5% over 10 years. Meaning that 95-97% of those patients receive no benefit. A fair unbiased presentation of this to patients is required to arrive at “shared decision making “.
I agree this study is a confusing mishmash and the authors likely spent a lot of time trying to create something significant from it.
Oddly, the reviewers (one of which is a consultant for CLEERLY, the CCTA AI) seem quite enthusiastic about it.
One critique of your critique... Your wrote: So the conclusion that “patients without CAD have no benefit from statins” goes against more than 20 trials of statin therapy as primary prevention. When you make big conclusions, you should have strong data. "
The statin trials define patients without CAD as those without clinical ASCVD, such as MI, stent, CABG. They haven't used subclinical coronary atherosclerosis which can be quite advanced in patients without clinical events.
Patients with advanced subclinical CAD are often at higher risk than those patients who have had events but are being treated optimally with medical therapy.
This trial (I presume) is using CCTA data to say that patients have no CAD.
This defines an entirely different population who truly are at a very very low risk of clinical CAD events.
Mark Twain was right. 1982. I was up all night in the seven bed CCU. Two deaths. Still in their rooms. EKG paper strewn everywhere. The rest of the people with Swan-Ganz catheter's getting IV nitroglycerin and morphine. A few got TPA as part of a study. No stents. Commonality men, 50 to 60 years of large STEMI. Fast forward 2025. How many ruptures of the ventricle, ventricular septal defects and blown papillary muscles are in the ICU every night?? Now mortality is down what 30 to 40%..Average age of admit?
Social media would make you think it was Magic, and that statins are another example of big pharma trying to steal from the population. I hope we don't go back to the future. My LDL was 200- now very low. I say thank you
As I’ve said before, where have the decent editors gone? That even a sub-journal of JACC would allow the type of conclusion language as was used with this paper, given the methodology of this paper, is gobsmacking.
Always appreciate you digging into the weeds (and supplements) of papers. It makes no sense when “any” use of X (including a very low prevalence) would exert a larger clinical effect than a higher prevalence of use. It flies in the face of the basic pharmacology principle of dose response.
Their “10% increase in use” is simply based on filled prescription days. We know nothing about dose (or even mean dosage prescribed). We know nothing about delta LDL. For all we know, this simply reflects the effect of very poor compliance with homeopathic statin doses.
All in all, this paper is a gong show that serves no purpose other than to feed the confirmation biases of those who are given to those sorts of proclivities.
I can’t imagine an instance when I would take a statin, or recommend someone else take a statin.
The odd thing is, that when you take statins, you have side effects. They are very, very common in a sizable percentage of people taking them, just an empirical guess 5 - 15%.
But when you look at the studies, side effects are very rare. There is so much bias, so much.
“Importantly, despite the small reductions in nonfatal heart attacks and strokes, statins were not associated with a reduction in serious illness overall (relative risk = 0.99; 95% confidence interval, 0.94 to 1.04).4 Adverse events from statin use include myalgia and new-onset diabetes at a rate of 4.8% (number needed to harm [NNH] = 21) and 0.49% over five years (NNH = 204), respectively.5,6 Other adverse events, although often reported, have not been well studied.”
Source: https://thennt.com/nnt/statins-persons-low-risk-cardiovascular-disease/
Your link is about patients at low risk for CV disease. This is not the same as “no CAD”. For example, one could have no CAD yet be at high risk due to age, hypertension, diabetes and smoking. This person benefits from a statin to lower risk of MACE.
The linked website does try at multiple points to make a distinction btw people who are high risk/FRS >20%, and those who are not.
However, I’m not sure if the commentator who linked to it would be discerning enough to perceive that distinction.
Good thing you’re not a doctor then.
Look up SAMSON trial.
Key Limitations of SAMSON
Selective participant pool:
SAMSON enrolled only people who had reported symptoms within two weeks of starting statins, which excluded longer-term or delayed adverse effects. This design bias made the study more convenient logistically but less representative of the general population of statin users, where side effects may appear months after initiation.
Single drug and dose:
The trial tested only atorvastatin 20 mg daily, which limits generalizability. Responses might differ for other statins (e.g., simvastatin, rosuvastatin) or for higher doses often used in secondary prevention.
Short treatment periods:
Each trial phase lasted only one month. Muscle or fatigue-related side effects could develop over longer durations, meaning subacute or cumulative effects weren’t captured.
Limited sample size:
The study involved only 60 participants, which restricts statistical strength and makes it difficult to detect small differences between statin and placebo periods.
Interpretive Concerns:
The nocebo framing—though likely valid for some participants—may have encouraged overgeneralization that statin side effects are mostly psychological. Some clinicians argue that downplaying genuine
Fair summary of the limitations. This is the only RCT on the question, to my knowledge.
yes I have reviewed it extensively. So what?
Interesting how people who have no argument simply attack me because I'm not a doctor. I'm glad I'm not a doctor. I can think for myself once in awhile, and very few doctors can.
Slow your roll with the whining, bud. Where was the attack? Merely pointing out facts.
If you don’t want a statin, that’s your choice.
You shouldn’t be recommending any treatment of anything to anybody, since you’re not a doctor. Statin, or otherwise. Assuming you actually recognize your limitations.
As always, erudite and well written, thank you. But, respectfully disagree, Dr. M. First, too much causal language: “the 10% increase in statins resulted in a 5% lower rate of events.” As you know, virtually all changes in the study are likely healthy user bias, and definitely associations. Second, I beg you to reassess statin data through the lens of true benefit. The great majority of ‘benefit’ is in ‘revascularization’, something you have rightly pointed out is not a benefit at all. At primary prevention control rates mortality—the real reason patients take the drug—is totally unchanged. Meanwhile, non-fatal MI is a false and often misleading surrogate, and statin harms are very real and virtually always omitted from such discussions. Looking forward to your next piece, but fear your statin advocacy is misled by clever CTT (i.e. industry) hand-waving.
Statistical reanalysis of this study is illuminating. Sensible Medicine is doing a fine job.
The bottom line in the current conclusions about statin use for asymptomatic patients is that most accrue a mild ARR of MACE Of 3-5% over 10 years. Meaning that 95-97% of those patients receive no benefit. A fair unbiased presentation of this to patients is required to arrive at “shared decision making “.