Your thought on IMS III: Endovascular Therapy after IV t-PA vs tPA Alone

soulofmpatel · Feb 15, 2013

If you have not read it already, please check out the following article in NEJM:

"Endovascular Therapy after Intravenous t-PA versus t-PA Alone for Stroke"

http://www.nejm.org/doi/full/10.1056/NEJMoa1214300#t=article

Here are some summary points:

1) thrombectomy procedure start time </= 5 hours after last known normal
2) NIHSS >/= 10 for part of the trial and >/= 8 for the remainder
3) Large vessel thrombus
4) primary outcome = modified rankin scale </= 2 at 3 months
5) Devices used were penumbra and mercy. only 4 solitaire cases in the trial.
6) Trial stopped due to futility; no significant benefit of modified rankin or mortality
7) Weak nonsignificant trend toward greater benefit if shorter embolectomy time
8) Discussion notes IV tPA recanalization rate of 40% for M1 thrombus based on modern data with angiography
9) Two groups had similar hemorrhage rate (embolectomy does not seem to increase hemorrhage rate)

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Some questions for you guys:

1) What kind of subjective experiences do you have with embolectomy?
2) Are you surprised about the relatively high recanalization rates with IV tPA compared to historical data?
3) How does this change your views toward embolectomy and how we should practice stroke neurology?

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My quick point:

I think this is a reasonably well done controlled negative trial which significantly dampens my enthusiasm for embolectomy. I have many negative subjective experiences and few positive experiences, so I am not surprised by the results.

I think that we should go forward as follows:

We should only do embolectomy in the setting of a clinical trial with the following criteria

a) With or without IV tPA beforehand
b) groin puncture time </= 4 hours from last known normal time. Recanalization time </= 4.5 hours (procedure to be aborted otherwise)
c) NHSS >/= 8
d) noncontrast CT without significant ischemic injury (could use ASPECT score?)
e) Do not waste time doing multimodal imaging
f) Improve our CT to groin puncture time with dedicated experienced staff and protocolized transport and prepping.

I believe that there is a good chance to show benefit of these procedures in highly selected patients using the solitaire and other new devices, and after a positive trial, we could consider expanding the patient population

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Please note that I am a neurology resident, and I am not an expert in stroke neurology.

Please disclose any financial or research incentives if you post in this thread

typhoonegator · Feb 15, 2013

All about recanalization time. Getting groin puncture means nothing if you screw around with the Penumbra device for another 2 hours trying to get the shuttle into the neck before you get the clot out.

Agree though, that multimodal imaging seems to be falling by the wayside and shouldn't be used given the time constraints.

We do a lot of cases, and the time to recan we are seeing with Trevo and Solitaire are far superior. Not that this means we ultimately are doing the right thing for everyone, but I think we are at least on a better track than we had been previously.

The high recan rate with tPA alone flies in the face of what a lot of stroke docs expected. Given that the trial was stopped early, not clear if this could be a statistical vagary or if we should expect better recan rates with IV tPA alone than we commonly think we should.

Disclosure: intensivist, acute stroke doc, not endovascular, don't get money from their procedures.

neglect · Feb 17, 2013

soulofmpatel said:
If you have not read it already, please check out the following article in NEJM:

This is sort of like asking a physicist to read some Einstein. If anyone here other than med students with a passing interest in neurology hasn't read this, then you don't do stroke.

1) What kind of subjective experiences do you have with embolectomy?
2) Are you surprised about the relatively high recanalization rates with IV tPA compared to historical data?
3) How does this change your views toward embolectomy and how we should practice stroke neurology?

1. Like everyone's. Sometimes good. Sometimes amazing. Sometimes bad. Sometimes amazingly bad. Sometimes nothing.
2. No. 1/5 by the time they get to the cath lab? No way. I'm surprised there were not more re-canalizations. I didn't know that 8 mm was the cut-off between a clot size that would respond to re-canalization and one that would not, that's valuable data.

Still, this is a major problem for endovascular-stroke. As stroke has progressed, I've personally seen door to needle times go down and outcomes have directly changed as a result. When your "placebo" group does better, then it is harder to demonstrate efficacy.

3. This changes everything. In the past, we operated with no data. And best wishes, device maker money, biases of all kinds filled in the gaps in our knowledge. Some did not keep a mind filled with healthy skepticism. That's over. I would say that we can no longer ethically and responsibly offer patients with anterior circulation these interventions unless they are part of a clinical trial. Period.

One could make the argument that because if you limit the trial to the very early, within 2 hours of onset say, with a demonstrated anterior clot on CTA (and nevermind about the perfusion scan, that's always been hocus pocus to me and now it's been demonstrated, thanks to the failed MR rescue trial) to go to endovasc suite. I would say this is a mistake though, with only a shred of supporting evidence. Much better to put them into a trial, any trial.

In short, endovascular is in a very bad place.

I have nothing to disclose. I'm a neurologist, no money comes to me from these device makers or from the procedures.

omarsaleh66 · Feb 18, 2013

I think they should not have suspended the trial
So many changes were made during the trial
- 256 participants were randomized even before CTA was heavily being used and NIHSS scores of 8 and 9 were being included
- Initially the IA group was getting 2/3 dose of tPA until July 2011 compared to the standard dose of tPA of the tPA only group
-Solitaire (stent retriever) was just starting to get used and the trial was suspended

Future trials can focus on
- IA therapy for large arterial thrombus (8mm or greater) and more severe strokes which the IMS III trial showed some promise but no statisical significance however this could be a subset of patients for future study
- Better devices such as stent retrieval devices + tPA vs tPA alone
- More focus on recanlization time. The IMS III trial had a delay of 32 minutes compared to the IMS I trial.

Disclosures:
None. IR fellow with no plans to do neurointerventions in the future. However very interesting topic in the IR/NIR community

neglect · Feb 19, 2013

omarsaleh66 said:
I think they should not have suspended the trial
So many changes were made during the trial
- 256 participants were randomized even before CTA was heavily being used and NIHSS scores of 8 and 9 were being included
- Initially the IA group was getting 2/3 dose of tPA until July 2011 compared to the standard dose of tPA of the tPA only group
-Solitaire (stent retriever) was just starting to get used and the trial was suspended

Future trials can focus on
- IA therapy for large arterial thrombus (8mm or greater) and more severe strokes which the IMS III trial showed some promise but no statisical significance however this could be a subset of patients for future study
- Better devices such as stent retrieval devices + tPA vs tPA alone
- More focus on recanlization time. The IMS III trial had a delay of 32 minutes compared to the IMS I trial.

Disclosures:
None. IR fellow with no plans to do neurointerventions in the future. However very interesting topic in the IR/NIR community

I know some of the people on the DSMC and they did not make the decision lightly. The trial was futile and had no chance of showing benefit. That's reason enough to stop it.

Changes were made during the trial so that the "latest adn greatest" device could be used. This was done to give endovascular therapies every possible advantage in showing efficacy. The trial bent over backwards so that endovasc could show benefit. But it didn't.

Future trials will be restricted to very select cases, as you say. This will limit enrollment. Eventually we will likely find small subpopulations of patients who should go to endovascular for acute stroke. But at this point, it is impossible to say who. Personally I'd speculate that basilars and those with NIHSS >20 who have a clot, who can be on the table in 2 hours from onset. But in the past most people's speculation was dead wrong - which is the biggest lesson of all.

The future of stroke is not going the way of MI.

soulofmpatel · Feb 19, 2013

Thank you for your replies.

I would like to think that neurologists are different from cardiologists in certain fundamental ways. We are not cowboys. We did not enter this field for the high procedure reimbursements.

In my opinion, the history of interventional cardiology is marred by proliferation of procedures in the face of negative trials (COURAGE, etc)

So presuming that the majority of you are in agreement with me and NEGLECT [that future embolectomy should be limited to highly selective clinical trials], was it immoral to do embolectomy with an 8 hour time window outside of clinical trials based on safety data alone? Did we "put the cart before the horse"? [to quote one of the residents here on SDN].

I must admit that my experience with embolectomy has contributed to my increasing skepticism and cynicism of stroke neurology and allopathic medicine in general.

donesoon · Feb 20, 2013

As a resident going into Stroke/INR, I chose the field not for its high reimbursement but for the potential of taking stroke patients destined for severe disability or death, treating their disease, and watching them walk out of the hospital. I think my experience with embolectomy has been the opposite of yours, soulofmpatel-- while there have been plenty of patients who haven't improved despite complete recanalization, I've also seen more than a handful of IV TPA-treated patients that come in with persistent large vessel, M1/2 occlusion and NIH >12 who are recanalized with 1 pass of SOLITAIRE and literally walk out the door a few days later with no deficits. One could argue based on the present evidence that an equal proportion of only IV treated patients would do the same. Perhaps, but I am not completely soured on the future of endovascular treatment yet. Good thing, I guess, or I should be looking for another fellowship.

The results of IMS-3 (and, to a lesser extent, SYNTHESIS) are certainly disappointing, but it reminds me of the back and forth with PCI after acute MI over the past 30 years. While early PCI and door-to-balloon times are the focus today, in the 80s thrombolytics were the primary treatment and RCTs performed in the late 80s did not show benefit of early PCI after thrombolytic therapy. This discrepancy was confusing to cardiologists then, as the supposed benefits of endovascular clot retrieval are to us now. Of course, in the early 90s a plethora of new RCTs came out showing benefits of PCI over thrombolytics, and now most would agree early reperfusion with PCI is preferable over thrombolytic treatment.

I don't say this to dispute the validity of IMS results or to directly compare interventional treatment of stroke with MI. I agree that the clinical trend should swing back to the side of endovascular treatment in the setting of trials, to identify the patients who will benefit from interventional therapy. I have no idea what my practice will look like in 10 years and accept the possibility that stroke treatment may not be part of it. On the other hand, I'm not buying into the "end of endovascular treatment as we know it" just yet. I'll need a few more years and futile trials before my enthusiasm is completely extinguished.

neglect · Feb 21, 2013

soulofmpatel said:
I would like to think that neurologists are different from cardiologists in certain fundamental ways. We are not cowboys. We did not enter this field for the high procedure reimbursements.

In my opinion, the history of interventional cardiology is marred by proliferation of procedures in the face of negative trials (COURAGE, etc)

I'd say that most are not cowboys. Most did not enter the profession for high procedure reimbursements. But some did. And despite these characteristics, they found themselves fish out of water until their endovasc fellowships. I agree with you about cardiology.

soulofmpatel said:
So presuming that the majority of you are in agreement with me and NEGLECT [that future embolectomy should be limited to highly selective clinical trials], was it immoral to do embolectomy with an 8 hour time window outside of clinical trials based on safety data alone? Did we "put the cart before the horse"? [to quote one of the residents here on SDN].

We were operating from a level of profound ignorance, all the deeper for us not realizing how ignorant we were. Hard and not useful to look backwards.

soulofmpatel said:
I must admit that my experience with embolectomy has contributed to my increasing skepticism and cynicism of stroke neurology and allopathic medicine in general.

The dignity of our profession hinges on our response to the data.

donesoon said:
As a resident going into Stroke/INR, I chose the field not for its high reimbursement but for the potential of taking stroke patients destined for severe disability or death, treating their disease, and watching them walk out of the hospital. I think my experience with embolectomy has been the opposite of yours, soulofmpatel-- while there have been plenty of patients who haven't improved despite complete recanalization, I've also seen more than a handful of IV TPA-treated patients that come in with persistent large vessel, M1/2 occlusion and NIH >12 who are recanalized with 1 pass of SOLITAIRE and literally walk out the door a few days later with no deficits. One could argue based on the present evidence that an equal proportion of only IV treated patients would do the same. Perhaps, but I am not completely soured on the future of endovascular treatment yet. Good thing, I guess, or I should be looking for another fellowship.

The results of IMS-3 (and, to a lesser extent, SYNTHESIS) are certainly disappointing, but it reminds me of the back and forth with PCI after acute MI over the past 30 years. While early PCI and door-to-balloon times are the focus today, in the 80s thrombolytics were the primary treatment and RCTs performed in the late 80s did not show benefit of early PCI after thrombolytic therapy. This discrepancy was confusing to cardiologists then, as the supposed benefits of endovascular clot retrieval are to us now. Of course, in the early 90s a plethora of new RCTs came out showing benefits of PCI over thrombolytics, and now most would agree early reperfusion with PCI is preferable over thrombolytic treatment.

I don't say this to dispute the validity of IMS results or to directly compare interventional treatment of stroke with MI. I agree that the clinical trend should swing back to the side of endovascular treatment in the setting of trials, to identify the patients who will benefit from interventional therapy. I have no idea what my practice will look like in 10 years and accept the possibility that stroke treatment may not be part of it. On the other hand, I'm not buying into the "end of endovascular treatment as we know it" just yet. I'll need a few more years and futile trials before my enthusiasm is completely extinguished.

1. Anecdotes ("more than a handful" indeed!) do not trump data. To even suggest this implies the most primitive sort of mind. Grow up. Fast. Medicine needs informed and mature minds.
2. The brain is not the heart. The differences lie in the tissue beds and their response to ischemia and the vessels that feed them. While you say you don't want to "directly compare" stroke and MI, that's exactly what you did. Better to omit the entire section.
3. Run and do not walk away from endovascular fellowship. The field was already glutted before we knew about the failure of interventions in acute stroke. At this point, at best, only a very few stroke cases will go to endovasc (how many basilars, MCA >8 mm come in < 2 hours in a month?). I say at best, because even here there was a trend but not significance. You need to reflect on this yourself, because your fellowship director will be eager to have you take call and do scut for a few years. They don't care about you adn your future career as much as you do.
4. Regardless of your choices, the writing is on the wall. Don't forsake the rest of neurology. Training in this subspecialty will make you a stroke neurologist and perhaps OK at critical care, but I doubt you will be able to reside purely in the subspecialty. Stay OK at the remainder of neurology.

Strokeguy · Mar 9, 2013

Disclaimer - I am a vascular neurologist who was actively involved in both IMS3 and MRRESCUE.
It is a complete misperception to equate the brain and the heart. More than anything else, the fact that time windows to treat ischemia in the brain is much shorter than the heart makes a significant difference in care delivery. So anyone giving examples of 'how acute coronary care evolved from thrombolytics to endovascular' is the road map for stroke essentially needs to consider practical issues in acute stroke care.
Cardiologists were able to proceed in this direction because of many different reasons - ECG which is done at site by EMS (whereas we need a CT head which can be done only in the ER - CT equipped ambulances as in some parts of europe are not practical economically). If we call INR for every pt with acute neuro deficit picked up by EMS prior to doing a CT, interventionists will spend their life on the road !! Even with best available resources the logistics of being able to open the artery much earlier than envisioned in IMS3 and MRRESCUE are challenging. These trials show that overall the number of pts who (in real practical situations) would benefit from IAT (if at all) is much less than prior perceptions.
On the other hand the results of CLEAR-ER is encouraging. This is still a phase-2 trial, but the potential of other numerous medical therapies that can be initiated quickly in the ER as well as via telemedicine is much more than IAT. As mentioned by another keyspeaker (from the UK) at ISC and in the editorial by Dr Chimowitz in NEJM - IAT is not the only potential therapy - desmoteplase, TNK, sonothrombolysis, CLEAR are all very promising therapies that can be applied practically; we have to see what the trials show though.
Any neurologist planning a career on INR alone is making a huge mistake. At least stroke medicine has changed significantly and permanently after these trials. It is not the end of INR in stroke, but certainly highlights the limited potential role it will play in stroke care (since future INR stroke trials will have an even more selective pt population).

neglect · Mar 12, 2013

Strokeguy said:
Disclaimer - I am a vascular neurologist who was actively involved in both IMS3 and MRRESCUE.
It is a complete misperception to equate the brain and the heart. More than anything else, the fact that time windows to treat ischemia in the brain is much shorter than the heart makes a significant difference in care delivery. So anyone giving examples of 'how acute coronary care evolved from thrombolytics to endovascular' is the road map for stroke essentially needs to consider practical issues in acute stroke care.
Cardiologists were able to proceed in this direction because of many different reasons - ECG which is done at site by EMS (whereas we need a CT head which can be done only in the ER - CT equipped ambulances as in some parts of europe are not practical economically). If we call INR for every pt with acute neuro deficit picked up by EMS prior to doing a CT, interventionists will spend their life on the road !! Even with best available resources the logistics of being able to open the artery much earlier than envisioned in IMS3 and MRRESCUE are challenging. These trials show that overall the number of pts who (in real practical situations) would benefit from IAT (if at all) is much less than prior perceptions.
On the other hand the results of CLEAR-ER is encouraging. This is still a phase-2 trial, but the potential of other numerous medical therapies that can be initiated quickly in the ER as well as via telemedicine is much more than IAT. As mentioned by another keyspeaker (from the UK) at ISC and in the editorial by Dr Chimowitz in NEJM - IAT is not the only potential therapy - desmoteplase, TNK, sonothrombolysis, CLEAR are all very promising therapies that can be applied practically; we have to see what the trials show though.
Any neurologist planning a career on INR alone is making a huge mistake. At least stroke medicine has changed significantly and permanently after these trials. It is not the end of INR in stroke, but certainly highlights the limited potential role it will play in stroke care (since future INR stroke trials will have an even more selective pt population).

I'm in full agreement, I just wanted to add a few minor things:

There are two ways in which people compare endovascular to cardiology. The first is the stupid way, which reveals the one making it as either a simpleton or in the grip of delusion: stroke is an MI of a brain vessel. Of course this is stupid. Nothing more needs to be said. The second is the smart way: stroke therapy is evolving like MI. This also seems stupid at first blush, but if you realize how tenuous PCI's grip on evidence based medicine is, then you must take a closer look. Perhaps this says more about how terrible interventional cardiology is than any sort of model for stroke care. That said, I think what this means is that stroke might end up like interventional cards: initial negative studies followed by marginally positive studies that supported an entrenched confirmatory bias and financial incentives.

I think a few things will make that idea fail. First of all, doctors are no longer in the driver seats. Insurance carriers are. We've lost power in part because of these excesses and the external costs we produce: if doctors charge 500 bucks to put in a 10,000 dollar device, they aren't going to worry about the societal problems, they're going to try to live up the patients to insert the device into. Second, medicine is hugely more data driven than it was even 10 years ago. Thirdly, I don't see that the brain will follow the heart. There are tons of logistical problems that just makes getting thrombolysis for stroke difficult >>>>> MI as pointed out above. Not just the logistical issues but differences in tissue sensitivity and vessel histology/anatomy/disease and clots.

I have my own bias, which I struggle with. I never thought these interventions would work and I thought these interventions were being done under futile circumstances nearly all the time. I just didn't know how right I was. But to take IMSIII as the final support to my nihilism would be just as foolish as it was to root into the IMSIII data to find a sliver of benefit in a sub-sub-sub group analysis to feed a preconceived notion that needs feeding. There might be patients for whom endovascular is appropriate. But it isn't for all, not even for most, nor for a plurality.

What do you guys think about what the future holds?

Strokeguy · Mar 13, 2013

I think when a lot of trials are complete over the next few years - including the new endovasc trials as well as trials on new thrombolytic agents - DIAS in particular and then the planned new tenecteplase trials (see NEJM), we will move towards a more algorithm based approach on acute stroke management. Finally we will be able to have fewer pts who could/would benefit from mech thrombectomy. This is after CLEAR, sonothrombolysis ... etc are done. End result is likely to be faster recanalization and fewer pts needing endovasc therapy (though there will be pts who would and certainly benefit from it).
Again, this will all be driven by the shorter time windows to reperfuse the ischemic brain.

DD214 · Mar 15, 2013

Looks like we'll have a few more decades of trying to find slightly better ways to try iceskating uphill.

Strokeguy · Mar 15, 2013

Not several decades. Some of these are done with phase2 and well into phase3. Again - why is the process so slow - people are resorting to off-label endovasc therapies than enrolling. Things are different in europe though since there is no financial incentive. This has certainly helped many trials.

soulofmpatel · Apr 2, 2013

Excellent replies, especially strokeguy and neglect.

Stroke guy: It seems to me that off-label endovascular therapy actually contributes to slowing down the development of the science. If I were a stroke attending, I would make it my policy to only do an intervention in the setting of a clinical trial (with possible rare exceptions of say a person with LKN time 1 hour ago, not a candidate for IV tPA, daytime hours with interventionalists present, no early ischemic signs on CT, and large vessel thrombus with NIHSS > 14)

Neglect: would you say that doctor have deservingly lost their power due to abuse of the system and failure to take into account cost

typhoonegator · Apr 2, 2013

When asked at AAN last week, only a handful of people in an audience of about 3,000 said they would offer endovascular therapy outside of a trial, as long as trials were readily available. So you're in good company.

The issue many have is that SWIFT-prime has very stringent inclusion criteria, and there is not a lot else out there right this minute. However, individual centers can still put together inclusion criteria and informed consent for these subjects and rigorously compile the data for meta-analysis, which I would argue still constitutes trials work. As the user above posted, having willy-nilly out-of-trial use really does hamper the field, and we want to capture as much as we can while maintaining equipoise.

I would still offer compassionate use treatment in individual exceptional cases, however, but this should be an increasingly small percentage of the patients treated. Think M1 occlusion LSW 20 minutes ago in a young endocarditis patient who is already on the medicine service in house. And MERCI/PENUMBRA are basically off the table now, if the lesion can't be reached and treated with the Solitaire or Trevo devices, then I don't think I would offer anything.

neglect · Apr 3, 2013

soulofmpatel said:
Excellent replies, especially strokeguy and neglect.

Stroke guy: It seems to me that off-label endovascular therapy actually contributes to slowing down the development of the science. If I were a stroke attending, I would make it my policy to only do an intervention in the setting of a clinical trial (with possible rare exceptions of say a person with LKN time 1 hour ago, not a candidate for IV tPA, daytime hours with interventionalists present, no early ischemic signs on CT, and large vessel thrombus with NIHSS > 14)

Neglect: would you say that doctor have deservingly lost their power due to abuse of the system and failure to take into account cost

I think it is reasonable to use ia procedures if someone can't get iv tpa for whatever reason. No trials im aware of have shown is procedures to be inferior to iv, yet. Your criteria for someone to be taken to the cath lab are as reasonable as any. Which is to say that no one really knows, and some only pretend to know.

And I do think that the sins of past doctors are being visited upon the field now. Doctors can no longer declare by fiat that they know it works. Surgeries are being evaluated like medicines. Some of this is for the best, because the moment Medicare stops paying for these things, stroke has a chance to actually advance.

typhoonegator said:
When asked at AAN last week, only a handful of people in an audience of about 3,000 said they would offer endovascular therapy outside of a trial, as long as trials were readily available. So you're in good company.

More properly, only a handful had the balls to raise their hands. Many others have inertia. And so doctors are going to get crushed by payers yet again. We can't clean our own messes (and can anyone argue that things didn't get off the hook? Or that stroke isn't a mess?), so someone is going to have to do it for us. Pathetic.

typhoonegator said:
The issue many have is that SWIFT-prime has very stringent inclusion criteria, and there is not a lot else out there right this minute. However, individual centers can still put together inclusion criteria and informed consent for these subjects and rigorously compile the data for meta-analysis, which I would argue still constitutes trials work. As the user above posted, having willy-nilly out-of-trial use really does hamper the field, and we want to capture as much as we can while maintaining equipoise.

The lesson we have to learn is that case series lie. Non-blinded raters have biases. Non-placebo-controlled trials are lesser forms of evidence. Just "capturing" data is just as bad as willy-nilly use because it is willy nilly itself.

typhoonegator said:
I would still offer compassionate use treatment in individual exceptional cases, however, but this should be an increasingly small percentage of the patients treated. Think M1 occlusion LSW 20 minutes ago in a young endocarditis patient who is already on the medicine service in house. And MERCI/PENUMBRA are basically off the table now, if the lesion can't be reached and treated with the Solitaire or Trevo devices, then I don't think I would offer anything.

Yeah, we're still going to be called for these cases. They are hard and rare.

soulofmpatel · Apr 8, 2013

typhoonegator said:
When asked at AAN last week, only a handful of people in an audience of about 3,000 said they would offer endovascular therapy outside of a trial, as long as trials were readily available. So you're in good company.

I was at that debate as well, but here is the problem...

I spoke to many stroke attendings at AAN regarding their feelings about the trial, and none of them stated that they would change their style of practice and do less thrombectomies.

It's the non-stroke neurologists who are conservative. The stroke neurologists are and always have been cowboys. They want to take action. They want to intervene. They convince themselves that they are saving neurons. They think that their institution is different-that their cases are more successful and not represented by trials. They think that their interventionalists are superheros with few complications. They remember every successful case like it was their opus magnus.

I know that the average patient in that trial was a better candidate for thrombectomy than the average patient getting a thrombectomy outside of a trial.

I am so cynical at this point. I honestly feel that financial incentives and psychology motivate medical practice rather than evidence and experience.

If the trial were even weakly positive, it would have been a huge news story and the field would have exploded.

Even IV thrombolytics are way overrated. Out of 12 clinical trials, only 4 have been positive (NINDS 2, ECASS III, PROACT, IST III), and only one has shown statistically significant benefit in the 3-4.5 hour subgroup of patients.

I'm not saying that we shouldn't give IV tPA to qualified patients, but it doesn't crack my top ten list for innovations in the history of stroke (which I would list as follows: aspirin, exercise programs, physical therapy, nutrition science/diets, warfarin, heparin, plavix, statins, echocardiography, telemetry; carotid endarterectomy/stenting is close to the top 10).

neglect · Apr 10, 2013

soulofmpatel said:
I was at that debate as well, but here is the problem...

I spoke to many stroke attendings at AAN regarding their feelings about the trial, and none of them stated that they would change their style of practice and do less thrombectomies.

It's the non-stroke neurologists who are conservative. The stroke neurologists are and always have been cowboys. They want to take action. They want to intervene. They convince themselves that they are saving neurons. They think that their institution is different-that their cases are more successful and not represented by trials. They think that their interventionalists are superheros with few complications. They remember every successful case like it was their opus magnus.

I'm not like that. I'm plenty aggressive, but I do not think we know better than trials.

Neurologists and endovascular docs are not cleaning up the house. Someone else will do it and it will be ugly. At this point, personally, I don't care. I've seen so much damn abuse of the system by endovasc, even after IMSIII and the rest, that I'm actually looking forward to the day when these procedures no longer get compensated outside trial conditions.

I share your cynicism. But IV tPA is the best stroke treatment ever. I've seen huge strokes melt with tPA. And this is backed up with the numbers. NNT 3 for small benefit. NNT 8 for huge benefit. Treat 20 cases, expecially early, and you'll regret ever saying that tPA is anything less than a wonder drug.

soulofmpatel · Apr 11, 2013

So...a 13% absolute benefit in terms of increasing the probability of a modified rankin of 0-1 in about 5% of stroke patients accounting for a <1% absolute benefit for all stroke patients qualifies as a "miracle drug."

Virtually any other intervention is going to be better than 1%. Quitting smoking for instance, starting a moderate exercise program, low glycemic index diet for a diabetic, starting ASA or a statin in a high risk patient-all of these destroy tPA.

Just because a drug is expensive and sexy does not mean it is a bonanza to society. I guarantee you that if the FDA pulls alteplase off the market, the nursing homes and rehab facilities won't notice the difference. Why not? Because no one will notice a 1% difference.

I've had plenty of success stories too, but the typical case is not NIHSS 20 > 0. Those cases are only occasional. Also, some strokes will improve spontaneously without tPA, but you would take full credit if you had administered the drug. The symptomatic intracranial hemorrhages also negate some of the successful cases. Clinicians are biased by ego, but blinded modified rankin evaluators at 3 months are not, which is why the data in clinical studies reveals only modest benefit of tPA in selected patients.

Lets not kid ourselves. We are not changing the face of stroke. A lot of our stroke patients do poorly. I'm not saying that care for stroke patients is futile, but in my view, acute interventions make up only a very small minority of the benefit we provide.

soulofmpatel · Apr 18, 2013

Wow...I can't believe I posted something so biting and controversial and got no replies

typhoonegator · Apr 18, 2013

soulofmpatel said:
Wow...I can't believe I posted something so biting and controversial and got no replies

I don't find your argument either biting or controversial. I'm fairly certain that Story Landis is not operating under the assumption that tPA is the last and best solution for the management of stroke and that we can stop NINDS funding for stroke research. And I've never met a cardiologist who said aspirin is not important because we have PCI. Even Ben Franklin said "an ounce of prevention is worth a pound of cure."

TPA is not great, but it's the best we have right now. Are you arguing we should just forget about it? Perhaps there is some other nuanced point you were making that I missed?

neglect · Apr 18, 2013

I took your comment in the same way I take Stalin's quote: "what do you call a single death? A tragedy. What do you call one million? A statistic."

tPA is sadly underused and when it is given it is too often wrongly given. Is it a panacea on a population wide level? Clearly not and I agree with you: at that level secondary and even primary stroke prevention makes more of a difference. But can it make a huge difference in a single someone's life? Yes.

soulofmpatel · Apr 19, 2013

typhoonegator said:
IAre you arguing we should just forget about it?

No

soulofmpatel · Apr 19, 2013

neglect said:
Clearly not and I agree with you: at that level secondary and even primary stroke prevention makes more of a difference. But can it make a huge difference in a single someone's life? Yes.

Of course I agree with you that it can make a huge difference in a single person's life. Of course, I've had such cases.

The point I'm making is that we're not changing the face of the disease. tPA is not comparable to other medical advances such as modern treatment of breast cancer where one can genuinely say, "wow...patients with this condition are doing overall much better than they were in the past!"

Your thought on IMS III: Endovascular Therapy after IV t-PA vs tPA Alone

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