I’m having a little trouble understanding the need for the extensive selection criteria. If the Impella device is meant for those with cardiac shock due to coronary artery occlusion, then it certainly will benefit some patients over others. This is par for the course in medicine. But why not just throw the gates open to those who might need it and then use subgroup analysis post hoc to determine which groups benefitted and which didn’t? Unless there is good reason to conclude that the device will harm someone or that it will not help them, why select the subject base so stringently? What am I missing?
Not having enough column inches to publish a properly concocted academic letter seems bizarre in 2024….especially when pixels are pretty cheap in the online version of a forum.
I don’t think any of the criticisms here necessarily invalidate the trial results. It does seem like the control arm event rate was higher here than with comparable MCS studies, and it would be interesting to look up what the authors had assumed the event rate would be. It could be that this trial simply studied a sicker population, as the study authors had intended. The letter authors noted the long study recruitment, which has also been mentioned by Drs. Mandrola and Prasad. This is certainly a very narrowly construed study population, but I think that goes to the external validity of the study without necessarily impugning its internal validity.
I wasn’t aware of the transplant angle. If more impella pts were alive at 180 days due to having had transplants, that definitely tempers any perceived benefit from the impella itself. However, the median age was 67, so it seems fewer than half of the cohort would’ve been transplant-eligible based on age alone.
I don’t see an issue with the protocol -specified “rescue” options for the control arm. No modality (drugs, IABP, or ECMO) has shown benefit. It doesn’t seem to me that the control arm was destined to inferior therapy, since nothing had been previously shown to be superior. However, Dr. Prasad’s point (in his video) about the differential results of the ITT vs per-protocol analysis does seem very curious. Per protocol is the lower bar, and there is something weird about a study clearing a higher bar while failing a lower one.
It would be wonderful if this study result could be replicated. But as it stands, I can live with these results as long as their application remains confined to the post STEMI shock population, without any creep into post arrest shock, or worse yet, “high risk PCI”. That would truly be egregious.
Dr Cheung, have you used this device before? What is your experience with it or that of your colleagues, if any? I’d love to know a “user’s” opinion on the matter.
Despite the snarky comment that NEJM has more readers than Substack (not true overall, but surely against this Substack, sadly) it is a marvelous idea to do this. There cannot be too many carefully considered opinions out there -- just too few. Thank you.
NEJM has become omniscient. But they could use a little help from comments by independent thinkers. I’ve stopped
Reading the editorials years ago because they just vomit back, but the article said. In the old day, Dr. Inglefinger would really tear up the articles.
Love that you are publishing thoughtful criticisms like this. I have seen several worthwhile rebuttals sent to journals to be rejected for reasons I don't think are in the public good. You can really provide a service to humanity here. Thank you
NEJM rejects the vast majority of letters submitted to it. It wasn't until the 5th letter on the subject of radiation from mammograms that they finally published. But, although the results of the study that we published in the NEJM are clear, Vinay Prasad continues to ignore them and still speaks of overdiagnosis of breast cancer where there are cancers caused by mammograms. Think what you will, but it's better to be published in NEJM than in Substack.
I’m having a little trouble understanding the need for the extensive selection criteria. If the Impella device is meant for those with cardiac shock due to coronary artery occlusion, then it certainly will benefit some patients over others. This is par for the course in medicine. But why not just throw the gates open to those who might need it and then use subgroup analysis post hoc to determine which groups benefitted and which didn’t? Unless there is good reason to conclude that the device will harm someone or that it will not help them, why select the subject base so stringently? What am I missing?
Thoughtful!
Not having enough column inches to publish a properly concocted academic letter seems bizarre in 2024….especially when pixels are pretty cheap in the online version of a forum.
I don’t think any of the criticisms here necessarily invalidate the trial results. It does seem like the control arm event rate was higher here than with comparable MCS studies, and it would be interesting to look up what the authors had assumed the event rate would be. It could be that this trial simply studied a sicker population, as the study authors had intended. The letter authors noted the long study recruitment, which has also been mentioned by Drs. Mandrola and Prasad. This is certainly a very narrowly construed study population, but I think that goes to the external validity of the study without necessarily impugning its internal validity.
I wasn’t aware of the transplant angle. If more impella pts were alive at 180 days due to having had transplants, that definitely tempers any perceived benefit from the impella itself. However, the median age was 67, so it seems fewer than half of the cohort would’ve been transplant-eligible based on age alone.
I don’t see an issue with the protocol -specified “rescue” options for the control arm. No modality (drugs, IABP, or ECMO) has shown benefit. It doesn’t seem to me that the control arm was destined to inferior therapy, since nothing had been previously shown to be superior. However, Dr. Prasad’s point (in his video) about the differential results of the ITT vs per-protocol analysis does seem very curious. Per protocol is the lower bar, and there is something weird about a study clearing a higher bar while failing a lower one.
It would be wonderful if this study result could be replicated. But as it stands, I can live with these results as long as their application remains confined to the post STEMI shock population, without any creep into post arrest shock, or worse yet, “high risk PCI”. That would truly be egregious.
Dr Cheung, have you used this device before? What is your experience with it or that of your colleagues, if any? I’d love to know a “user’s” opinion on the matter.
Despite the snarky comment that NEJM has more readers than Substack (not true overall, but surely against this Substack, sadly) it is a marvelous idea to do this. There cannot be too many carefully considered opinions out there -- just too few. Thank you.
NEJM has become omniscient. But they could use a little help from comments by independent thinkers. I’ve stopped
Reading the editorials years ago because they just vomit back, but the article said. In the old day, Dr. Inglefinger would really tear up the articles.
Relevant questions!
Keep them coming - sunlight is the greatest deodorant to the obfuscation within medicine
Love that you are publishing thoughtful criticisms like this. I have seen several worthwhile rebuttals sent to journals to be rejected for reasons I don't think are in the public good. You can really provide a service to humanity here. Thank you
“Not enough space” is weird - have an online supplement!
NEJM rejects the vast majority of letters submitted to it. It wasn't until the 5th letter on the subject of radiation from mammograms that they finally published. But, although the results of the study that we published in the NEJM are clear, Vinay Prasad continues to ignore them and still speaks of overdiagnosis of breast cancer where there are cancers caused by mammograms. Think what you will, but it's better to be published in NEJM than in Substack.