I don't mind medical reversals but do find it quite disruptive for patient care when we readily create guidelines which become not just guidelines, but the gold standard of care.
And just as we don't release marijuana users from jail after legalizing marijuana use, we don't reverse malpractice cases which were based on pre-reversal data.
Great review, John; thanks! I used to do CEAs routinely, until cardiologists started stenting aggressively. And though I had good results (no deaths or strokes), and enjoyed doing CEAs (they're a fun little procedure), I'm really not surprised by the null findings.
I'm curious whether any effects are seen if the data are limited to patients who met lifestyle benchmarks, e.g., the 50% of the patients with diabetes whose HbA1c level was in the target range. Not suggesting p-hacking, but wondering if there is evidence in the data that "treatment" via lifestyle modifications alone is more effective than either IMM and CAS/CEA, or how much more effective lifestyle modifications + IMM might be than IMM alone.
I am probably overly enamored with the potential benefits of imaging as a radiologist, but I think it would now be reasonable to attempt to further stratify risk of asymptomatic carotid artery disease from imaging correlates of plaque composition, i.e. ‘hard’ vs ‘soft’ plaque proportions and presence of intraplaque hemorrhage or ulceration.
No surprise that stenting carotid atherosclerotic lesions in asymptomatic patients provides the same benefit (none) as stenting coronary stenoses in patients with no symptoms or stable angina. But some of the recommendations that the authors give border on horrific. Specifically, they recommend "aggressive management of BP, lipids, and glucose". The great majority of these patients are going to be elderly. Risk of inducing hypotension or hypoglycemia should be enough contraindication but I can't even begin to express my bewilderment that any physician would recommend targeting lipid levels in the elderly.
After a stent or ectomy is there anticoagulant required? Warfarin or oral? If anticoagulant is necessary, how many adverse effects? What are the patients' lives like 1yr later or 5yr later for IMM vs procedure? With high dose stations, what are the complications and is compliance related to adverse effects? Do the IMM people eventually need a stent or ectomy?
Sonographer here. The threshold for stenting or endart is typically a stenosis of greater than 70%. Up until that point medical therapy and lifestyle changes are recommended. If a side is occluded the pt needs patent vertebral arts and a complete circle of Willis to encourage vascular flow through out the brain, otherwise infarction will occur. Pts are monitored for carotid art disease once it is found to ensure treatment is effective.
Stroke rates are low. But CAS (in experienced high volume centers) does seem to provide a real benefit, with a decent NNT, albeit statistically fragile.
I wonder about ASA use in IMM arm. Text mentioned antiplatelet use was comparable in all treatment arms, but details are in supplement which I haven’t looked at yet.
I’m curious about the poor target attainment for risk factor control in IMM arm. On one hand, there’s more bang to be had there. OTOH, if a diligent research team could not cajole people to take their meds sufficiently, that bodes less well in a real world setting. But I’d also like to see attained doses of various therapies.
In the end, it requires a discussion with the patient. Starting from asymptomatic state, are they willing to accept a real upfront stroke risk with CAS, in exchange for a real downstream benefit of reduced stroke?
155 centers, 600 patients in each intervention arm( CEA and CAS) average of 4 interventions per procedure per center.
All intervention patients received at least ASA long term, not clear that IMM patients had the same anti-platelet treatment.
20 % of the IMM only patients had either CES or CEA during the follow up period, listed as due to symptoms, progression of stenosis or patient preference. Reviewers were blinded, patients and clinicians were not.
Two separate IMM only control groups had dissimilar event rates that are not addressed, if control group rate was the same in each intervention arm the advantage of stenting would be minimal.
The immediate consequences of intervention of either type produced 17 adverse outcomes in asymptomatic patients.
No cost comparison offered or attempted. What is the optimal use of resources for society vs individual?
It's nice to see my biases confirmed. One of the biggest issues that I see is case finding in asymptomatic patient that go to screening clinics and expensive "life extension" centers that do Carotid ultrasound along with tests such as total body MRI. It should be pointed out that screening for asymptomatic carotid lesions has been discouraged for a long time but still gets done. Where it gets messier however is the patient with a lot of risk factors who might have had a symptomatic event. In my community endarterectomy is a very infrequent procedure so if I needed one I would like to have a surgeon who has a lot of experience
And of course, unsaid is in a midsize city that has a very good medical population because the spouses like to live here. I know someone who knows for a fact there's a wide variation in outcome with stenting. If I'm getting any procedure, I'm going to ask if they're enrolled in the registry and what their data is.
How were event rates so high? We consider these low risk lesions (1% event rates) but the trial showed 4 year event rates of 5.3-6% on medical therapy. Is that generalizable or was there some characteristic of the patient population that made them higher risk?
He didn’t write the risk of a stroke due to asymptomatic carotid stenosis was 1%, asymptomatic carotid stenosis cause 1% of all strokes from what he wrote.
There will be modest effect size(at most) in studies involving vascular issues where competing causes of disease are so prominent. They are isolating here the effect of intervening locally on a specific vascular territory when the macroscopic view tells you that the real issue is that the patient is generally at risk of any type of vascular insult. That is the power of focusing more on the medical intervention front where the goal is to intervene in a more comprehensive way.
Yes that is why it would be important to know if the stroke endpoint was limited to an ipsilateral territorial infarction to the carotid lesion as opposed to any regions and lacunar infarcts
One of my favorite books on this topic by Prasad & Cifu is a great primer on this topic.
https://www.goodreads.com/book/show/27207880-ending-medical-reversal
I don't mind medical reversals but do find it quite disruptive for patient care when we readily create guidelines which become not just guidelines, but the gold standard of care.
And just as we don't release marijuana users from jail after legalizing marijuana use, we don't reverse malpractice cases which were based on pre-reversal data.
So should I stop listening for a bruit on physical exam if the patient is not complaining of TIA?
Would seem so.
Great review, John; thanks! I used to do CEAs routinely, until cardiologists started stenting aggressively. And though I had good results (no deaths or strokes), and enjoyed doing CEAs (they're a fun little procedure), I'm really not surprised by the null findings.
I'm curious whether any effects are seen if the data are limited to patients who met lifestyle benchmarks, e.g., the 50% of the patients with diabetes whose HbA1c level was in the target range. Not suggesting p-hacking, but wondering if there is evidence in the data that "treatment" via lifestyle modifications alone is more effective than either IMM and CAS/CEA, or how much more effective lifestyle modifications + IMM might be than IMM alone.
I am probably overly enamored with the potential benefits of imaging as a radiologist, but I think it would now be reasonable to attempt to further stratify risk of asymptomatic carotid artery disease from imaging correlates of plaque composition, i.e. ‘hard’ vs ‘soft’ plaque proportions and presence of intraplaque hemorrhage or ulceration.
No surprise that stenting carotid atherosclerotic lesions in asymptomatic patients provides the same benefit (none) as stenting coronary stenoses in patients with no symptoms or stable angina. But some of the recommendations that the authors give border on horrific. Specifically, they recommend "aggressive management of BP, lipids, and glucose". The great majority of these patients are going to be elderly. Risk of inducing hypotension or hypoglycemia should be enough contraindication but I can't even begin to express my bewilderment that any physician would recommend targeting lipid levels in the elderly.
After a stent or ectomy is there anticoagulant required? Warfarin or oral? If anticoagulant is necessary, how many adverse effects? What are the patients' lives like 1yr later or 5yr later for IMM vs procedure? With high dose stations, what are the complications and is compliance related to adverse effects? Do the IMM people eventually need a stent or ectomy?
Sonographer here. The threshold for stenting or endart is typically a stenosis of greater than 70%. Up until that point medical therapy and lifestyle changes are recommended. If a side is occluded the pt needs patent vertebral arts and a complete circle of Willis to encourage vascular flow through out the brain, otherwise infarction will occur. Pts are monitored for carotid art disease once it is found to ensure treatment is effective.
amen
This is a challenging one.
Stroke rates are low. But CAS (in experienced high volume centers) does seem to provide a real benefit, with a decent NNT, albeit statistically fragile.
I wonder about ASA use in IMM arm. Text mentioned antiplatelet use was comparable in all treatment arms, but details are in supplement which I haven’t looked at yet.
I’m curious about the poor target attainment for risk factor control in IMM arm. On one hand, there’s more bang to be had there. OTOH, if a diligent research team could not cajole people to take their meds sufficiently, that bodes less well in a real world setting. But I’d also like to see attained doses of various therapies.
In the end, it requires a discussion with the patient. Starting from asymptomatic state, are they willing to accept a real upfront stroke risk with CAS, in exchange for a real downstream benefit of reduced stroke?
Fantastic review! Great application of evidence-based principles! Appreciate the time and effort taken to put this post together. Thank you🙏
Observations from the study data:
155 centers, 600 patients in each intervention arm( CEA and CAS) average of 4 interventions per procedure per center.
All intervention patients received at least ASA long term, not clear that IMM patients had the same anti-platelet treatment.
20 % of the IMM only patients had either CES or CEA during the follow up period, listed as due to symptoms, progression of stenosis or patient preference. Reviewers were blinded, patients and clinicians were not.
Two separate IMM only control groups had dissimilar event rates that are not addressed, if control group rate was the same in each intervention arm the advantage of stenting would be minimal.
The immediate consequences of intervention of either type produced 17 adverse outcomes in asymptomatic patients.
No cost comparison offered or attempted. What is the optimal use of resources for society vs individual?
Great study. Questions remain.
It's nice to see my biases confirmed. One of the biggest issues that I see is case finding in asymptomatic patient that go to screening clinics and expensive "life extension" centers that do Carotid ultrasound along with tests such as total body MRI. It should be pointed out that screening for asymptomatic carotid lesions has been discouraged for a long time but still gets done. Where it gets messier however is the patient with a lot of risk factors who might have had a symptomatic event. In my community endarterectomy is a very infrequent procedure so if I needed one I would like to have a surgeon who has a lot of experience
And of course, unsaid is in a midsize city that has a very good medical population because the spouses like to live here. I know someone who knows for a fact there's a wide variation in outcome with stenting. If I'm getting any procedure, I'm going to ask if they're enrolled in the registry and what their data is.
How were event rates so high? We consider these low risk lesions (1% event rates) but the trial showed 4 year event rates of 5.3-6% on medical therapy. Is that generalizable or was there some characteristic of the patient population that made them higher risk?
He didn’t write the risk of a stroke due to asymptomatic carotid stenosis was 1%, asymptomatic carotid stenosis cause 1% of all strokes from what he wrote.
There will be modest effect size(at most) in studies involving vascular issues where competing causes of disease are so prominent. They are isolating here the effect of intervening locally on a specific vascular territory when the macroscopic view tells you that the real issue is that the patient is generally at risk of any type of vascular insult. That is the power of focusing more on the medical intervention front where the goal is to intervene in a more comprehensive way.
Yes that is why it would be important to know if the stroke endpoint was limited to an ipsilateral territorial infarction to the carotid lesion as opposed to any regions and lacunar infarcts