Funny, I did think this was practice-changing. I knew flu infection was associated with increased risk of MI, so when an RCT showed decreased risk of MI with vaccine I thought, "Aha!" I tend to think we over-vaccinate young/healthy folks, but I do encourage people with other risk factors to vaccinate in order to reduce ASCVD events. In fact, this year I sent a mass message to patients at my practice discussing this study and recommending they walk in to get their flu shot if they are considered to be at high risk. I'm in America, I hate that we push the vaccine on the young and healthy folks, and that quality metrics are tied to the uptake of the flu vaccine - i really don't want to talk about it with a healthy young person. But I thought this data was compelling enough to move forward. If others disagree and want to do a follow-up study, I think that's reasonable. If the follow-up study contradicted this study, I would temper my enthusiasm.
Who thought this one up? Is there any biologically plausible mechanism by which influenza vaccine might benefit victims of MI? I suspect one can find a 2% difference in endpoints between groups investigating all kinds of irrational factors or "treatments".
Fascinating post. I vaguely remember this when it was published but wasn’t really on my radar (perhaps because it was obscured by Covid at the time).
The authors and editorialists make a strong case for flu vaccination in the post ACS population during flu season (September - February based on the protocol for northern hemisphere).
I do wonder about the stated caveat re: early stopping and exaggeration of effect size. I also wonder about the fragility index for the primary composite endpoint given it barely met statistical significance.
Considering Cochrane has stabilized flu vaccine studies because, see below, why is this even a thing?
“Currently, massive worldwide machinery is needed to produce new vaccines every year to address viral antigenic changes, and to address the poor persistence of the antibody response in individuals. However, the vaccination selection and production programmes are based on aetiological assumptions which are neither explanatory nor predictive, as shown in our reviews. Overall the largest dataset to have accumulated to date is from trials conducted in the population least likely to benefit from vaccines but most likely to produce immunity: healthy adults. In healthy adult trials a high serological response is matched by a very small clinical effect (71 healthy adults need to be vaccinated to prevent one of them experiencing influenza). This weak effect cannot be explained simply by the mismatch of vaccine antigens with wild virus ones. A larger effect is observed in children over the age of two (five children need to be vaccinated to prevent one case of influenza, although there is huge uncertainty around these estimates). There is little evidence on prevention of complications, transmission, or time off work. Other reviews have drawn similar conclusions.5”
I agree with the author that we need to break free from Camp 3.
More work is undoubtedly useful. I get angry when people say "at this point it would be unethical to do any more studies." I think people who say that must be approaching this from a religious perspective instead of from a scientific perspective.
The truth is that uptake is already quite low so a study that randomized half into vaccination would not decrease vaccination uptake. So how would such a study be unethical?
It is also possible that there is a seasonal benefit / detriment to vaccinating post-MI patients. Perhaps vaccination in October through February provides benefit but vaccinating in May through July provides harm? Probably not but how could we figure it out without more studies?
Are a lot of people getting vaccinated in May & June right now? Probably not, so how does running this study harm anyone?
No no no no no no no. We need to stop pushing all this stuff it's so irritating! We don't NEED to live to 100 !!
There is zero justification for this obsession with living longer and longer and longer. It is better to focus on better fewer years than more crappier years!!!!
We practice medicine for only 2 reasons: to help people live longer, and/or feel better. That’s it. If we are not doing at least one of those 2 things, we are doing it wrong. This study shows one of those things….with the statistical caveat of having been stopped early.
Also, these are 59 year-olds on average. I think “living longer” is a fairly relevant goal to such a cohort.
Disagree. Life is worth living. Even a suffering life has value. You are not God, you do not know what that 100 year old will be able to enjoy in their last days. Could be one more grandkid’s birthday, and that is enough.
But I do agree that flu shots should be a choice. I refuse flu shots right now, but I could see myself being 99 and willing to risk acute reactions for the 35% chance of reduced flu severity.
Do you really think the findings are plausible and real?
This year according to CDC the flu shot was 35% effective in southern hemisphere which by the time we had our flu season in the North, its efficacy was probably further down due to rapidly mutating strains..
Also are you suggesting we should vaccinate a patient having a STEMI in June? For what reason? By Nov, that is the flu season the antibodies have likely completely vanished past their half life.
This incomplete study needs to be replicated before any further conclusions are driven.
Hi, I read and enjoy Roger McFillin, Radically Genuine, not as evidence based as here so might not be what you are searching. He is certainly full of good questions and (norm) challenges I find.
Maybe not what you are looking for, but try Astral Codex Ten (and the old blog Slate Star Codex.) interesting psychiatric info, lots of other stuff mixed in. There is another blog called Polypharmacy that may be closer to what you want.
Camp Two seems the more nuanced and sensible approach to me.
- The trial wasn't powered for all-cause deaths (not even to the primary outcome due to the early stop) and barely reaches the statistical significant bar.
- There are some imbalances between groups (such as the placebo group having ~2% more STEMI) and <50% of the screened population was randomized, which is concerning for selection bias.
- It's not entirely biologic plausible to me that an influenza vaccine, which we already know that lacks efficiency because its influenza strain choices are kind of based on guessing (https://escholarship.org/uc/item/21v7x12q), would cause such a magnitude of lowering all-cause mortality.
- Related to the previous: Why didn't the authors report influenza confirmed infection and deaths related to influenza confirmed infection? It's one of the major outcomes I would like to know but wasn't reported. Since the Swedish and Danish registries are known for its data quality, I find it even more bizarre that they couldn't evaluate it.
I am not saying it is impossible that this results are true, but since it's a trial with some concerning issues, I would strongly like to see a replication of the trial.
Until then (maybe never), post-MI patients are a population where I am more inclined to favour influenza vaccines, but I won't push it very hard.
Especially in light of a supposed DEADLY NEW DISEASE RAPIDLY SPREADING (all lies or exaggeration) it’s questionable that ALL CAUSE deaths dropped. More proof Covid wasn’t as deadly nor to be feared like the PANICdemic pushed to disrupt and HARM peoples lives and livelihoods.
Whilst influenza vaccination doesn’t have a clear benefit in terms of hospitalization/mortality among elderly/young adults, this specific population seems to get benefit.
Perhaps a more nuanced effort to encourage its use in this specific population would be best given it’s not clear it’s warranted elsewhere, and blanket recommendations (rightly) drive distrust
Both Cochrane reviews looking at influenza vaccination in either healthy children or adults find no benefit for hospitalization or mortality. There is likely a benefit for preventing influenza, however this is potentially uncertain given differences in methods for determining infection. There also less effective for preventing influenza like illness (so getting ill with flu regardless of its cause) which is the most relevant measure given the uncertainty on actual influenza infection
"Whilst influenza vaccination doesn’t have a clear benefit in terms of hospitalization/mortality among elderly/young adults" I don't see this conclusion as drawn from the study you highlight. Is that a generally accepted proposition and can you point to indicative links?
Since flu vaccination spikes at age 65, you can do a regression discontinuity study. One exists. It finds no mortality benefit and trends towards increased mortality especially in males. I believe this more than any RCT. I fall into the camp of "this is not a plausible benefit". Intentially giving people an experience of acute inflammation after a heart attack sounds like a way to kill some people, IMO.
Meta-analyses of RCTs on this subjects seem conflicting.
But my question here is what happens if vaccination causes events in an acute window. That would automatically make SCCS studies report spurious benefit. (Nothing beats detecting harm and calling it benefit...) Also super weird is their sensitivity analysis which in one case excludes people who had acute CV events. This is the analysis where they reported the *most* benefit. The sensitivity analysis also says the benefit was driven only by particular flu seasons, even though their supplementary tables - at least to me - do not suggest those years had especially better concordance of vaccine strain. They also did no variation in their baseline defintion, which is probably the most important variable. Hard to believe any studies anymore..
One question I have in general is what followup windows do RCTs use? Are they at risk of censoring acute harm from vaccination?
Conclusion: The evidence favors the conclusion that the evidence favors no conclusion.
This is a jumble, and people will Rorschach the heck out of anything they want to.
Also, isn't there now some evidence that getting a flu vaccine every year actually reduces efficacy, and that it's only going to have its maximal (a dismal 40% or so?) effectiveness if it's administered only once every 3 - 5 years? If that's the case, and it were actually true that it was beneficial as hoped for in the IAMI study, what would you do with the patient that had their flu vaccine in the previous few years and an MI the next?
In my nonprofessional opinion flu vaccines are garbage products that no one should get in any scenario. There is definitely a lot of literature on the deleterious nonspecific effects of flu vaccines. In other words, they may increase your risk of getting other kinds of infections. I believe that - and possibly some other uncertain harms - are equalling out or outweighing any specific benefit flu vaccines have for the flu. And there is very little evidence on what happens if you get vaccinated multiple season in a row, but what is out there suggests you may be at increased risk even of the flu...
Funny, I did think this was practice-changing. I knew flu infection was associated with increased risk of MI, so when an RCT showed decreased risk of MI with vaccine I thought, "Aha!" I tend to think we over-vaccinate young/healthy folks, but I do encourage people with other risk factors to vaccinate in order to reduce ASCVD events. In fact, this year I sent a mass message to patients at my practice discussing this study and recommending they walk in to get their flu shot if they are considered to be at high risk. I'm in America, I hate that we push the vaccine on the young and healthy folks, and that quality metrics are tied to the uptake of the flu vaccine - i really don't want to talk about it with a healthy young person. But I thought this data was compelling enough to move forward. If others disagree and want to do a follow-up study, I think that's reasonable. If the follow-up study contradicted this study, I would temper my enthusiasm.
What was used as the placebo?
I am wary of a possible subtle switch to mRNA based flu shots that are in the plans.
Who thought this one up? Is there any biologically plausible mechanism by which influenza vaccine might benefit victims of MI? I suspect one can find a 2% difference in endpoints between groups investigating all kinds of irrational factors or "treatments".
I would happily volunteer for the unvaccinated cohort.:)
Fascinating post. I vaguely remember this when it was published but wasn’t really on my radar (perhaps because it was obscured by Covid at the time).
The authors and editorialists make a strong case for flu vaccination in the post ACS population during flu season (September - February based on the protocol for northern hemisphere).
I do wonder about the stated caveat re: early stopping and exaggeration of effect size. I also wonder about the fragility index for the primary composite endpoint given it barely met statistical significance.
Considering Cochrane has stabilized flu vaccine studies because, see below, why is this even a thing?
“Currently, massive worldwide machinery is needed to produce new vaccines every year to address viral antigenic changes, and to address the poor persistence of the antibody response in individuals. However, the vaccination selection and production programmes are based on aetiological assumptions which are neither explanatory nor predictive, as shown in our reviews. Overall the largest dataset to have accumulated to date is from trials conducted in the population least likely to benefit from vaccines but most likely to produce immunity: healthy adults. In healthy adult trials a high serological response is matched by a very small clinical effect (71 healthy adults need to be vaccinated to prevent one of them experiencing influenza). This weak effect cannot be explained simply by the mismatch of vaccine antigens with wild virus ones. A larger effect is observed in children over the age of two (five children need to be vaccinated to prevent one case of influenza, although there is huge uncertainty around these estimates). There is little evidence on prevention of complications, transmission, or time off work. Other reviews have drawn similar conclusions.5”
https://community.cochrane.org/news/why-have-three-long-running-cochrane-reviews-influenza-vaccines-been-stabilised
I agree with the author that we need to break free from Camp 3.
More work is undoubtedly useful. I get angry when people say "at this point it would be unethical to do any more studies." I think people who say that must be approaching this from a religious perspective instead of from a scientific perspective.
The truth is that uptake is already quite low so a study that randomized half into vaccination would not decrease vaccination uptake. So how would such a study be unethical?
It is also possible that there is a seasonal benefit / detriment to vaccinating post-MI patients. Perhaps vaccination in October through February provides benefit but vaccinating in May through July provides harm? Probably not but how could we figure it out without more studies?
Are a lot of people getting vaccinated in May & June right now? Probably not, so how does running this study harm anyone?
No no no no no no no. We need to stop pushing all this stuff it's so irritating! We don't NEED to live to 100 !!
There is zero justification for this obsession with living longer and longer and longer. It is better to focus on better fewer years than more crappier years!!!!
The mindset here is completely flawed.
Wait what?!?
We practice medicine for only 2 reasons: to help people live longer, and/or feel better. That’s it. If we are not doing at least one of those 2 things, we are doing it wrong. This study shows one of those things….with the statistical caveat of having been stopped early.
Also, these are 59 year-olds on average. I think “living longer” is a fairly relevant goal to such a cohort.
Disagree. Life is worth living. Even a suffering life has value. You are not God, you do not know what that 100 year old will be able to enjoy in their last days. Could be one more grandkid’s birthday, and that is enough.
But I do agree that flu shots should be a choice. I refuse flu shots right now, but I could see myself being 99 and willing to risk acute reactions for the 35% chance of reduced flu severity.
Do you really think the findings are plausible and real?
This year according to CDC the flu shot was 35% effective in southern hemisphere which by the time we had our flu season in the North, its efficacy was probably further down due to rapidly mutating strains..
Also are you suggesting we should vaccinate a patient having a STEMI in June? For what reason? By Nov, that is the flu season the antibodies have likely completely vanished past their half life.
This incomplete study needs to be replicated before any further conclusions are driven.
Why would we assume everyone will benefit from routine vaccination? This seems highly population specific. Not a logical conclusion.
Not on topic with the article, but I’m wondering if anyone has Substack recommendations for something similar to sensible medicine but for psychiatry?
Hi, I read and enjoy Roger McFillin, Radically Genuine, not as evidence based as here so might not be what you are searching. He is certainly full of good questions and (norm) challenges I find.
Psychiatry at the margins. By Awais Aftab who also has a column in Psychiatric Times
Mad in America
I concur
Maybe not what you are looking for, but try Astral Codex Ten (and the old blog Slate Star Codex.) interesting psychiatric info, lots of other stuff mixed in. There is another blog called Polypharmacy that may be closer to what you want.
Camp Two seems the more nuanced and sensible approach to me.
- The trial wasn't powered for all-cause deaths (not even to the primary outcome due to the early stop) and barely reaches the statistical significant bar.
- There are some imbalances between groups (such as the placebo group having ~2% more STEMI) and <50% of the screened population was randomized, which is concerning for selection bias.
- It's not entirely biologic plausible to me that an influenza vaccine, which we already know that lacks efficiency because its influenza strain choices are kind of based on guessing (https://escholarship.org/uc/item/21v7x12q), would cause such a magnitude of lowering all-cause mortality.
- Related to the previous: Why didn't the authors report influenza confirmed infection and deaths related to influenza confirmed infection? It's one of the major outcomes I would like to know but wasn't reported. Since the Swedish and Danish registries are known for its data quality, I find it even more bizarre that they couldn't evaluate it.
I am not saying it is impossible that this results are true, but since it's a trial with some concerning issues, I would strongly like to see a replication of the trial.
Until then (maybe never), post-MI patients are a population where I am more inclined to favour influenza vaccines, but I won't push it very hard.
Especially in light of a supposed DEADLY NEW DISEASE RAPIDLY SPREADING (all lies or exaggeration) it’s questionable that ALL CAUSE deaths dropped. More proof Covid wasn’t as deadly nor to be feared like the PANICdemic pushed to disrupt and HARM peoples lives and livelihoods.
This finding would align with the Cochrane review of a similar investigation (CVD Patients)
https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD005050.pub3/full?highlightAbstract=influenza%7Cinfluenz
Whilst influenza vaccination doesn’t have a clear benefit in terms of hospitalization/mortality among elderly/young adults, this specific population seems to get benefit.
Perhaps a more nuanced effort to encourage its use in this specific population would be best given it’s not clear it’s warranted elsewhere, and blanket recommendations (rightly) drive distrust
https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD004879.pub5/full?highlightAbstract=influenza%7Cinfluenz
https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD001269.pub6/full?highlightAbstract=influenza%7Cinfluenz
Both Cochrane reviews looking at influenza vaccination in either healthy children or adults find no benefit for hospitalization or mortality. There is likely a benefit for preventing influenza, however this is potentially uncertain given differences in methods for determining infection. There also less effective for preventing influenza like illness (so getting ill with flu regardless of its cause) which is the most relevant measure given the uncertainty on actual influenza infection
"Whilst influenza vaccination doesn’t have a clear benefit in terms of hospitalization/mortality among elderly/young adults" I don't see this conclusion as drawn from the study you highlight. Is that a generally accepted proposition and can you point to indicative links?
Since flu vaccination spikes at age 65, you can do a regression discontinuity study. One exists. It finds no mortality benefit and trends towards increased mortality especially in males. I believe this more than any RCT. I fall into the camp of "this is not a plausible benefit". Intentially giving people an experience of acute inflammation after a heart attack sounds like a way to kill some people, IMO.
Meta-analyses of RCTs on this subjects seem conflicting.
https://www.sciencedirect.com/science/article/pii/S0264410X24000537
https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD005050.pub3/full
https://www.ahajournals.org/doi/10.1161/JAHA.120.019636
Self-controlled case series claims benefit:
https://www.nature.com/articles/s41541-024-00969-y
But my question here is what happens if vaccination causes events in an acute window. That would automatically make SCCS studies report spurious benefit. (Nothing beats detecting harm and calling it benefit...) Also super weird is their sensitivity analysis which in one case excludes people who had acute CV events. This is the analysis where they reported the *most* benefit. The sensitivity analysis also says the benefit was driven only by particular flu seasons, even though their supplementary tables - at least to me - do not suggest those years had especially better concordance of vaccine strain. They also did no variation in their baseline defintion, which is probably the most important variable. Hard to believe any studies anymore..
One question I have in general is what followup windows do RCTs use? Are they at risk of censoring acute harm from vaccination?
Conclusion: The evidence favors the conclusion that the evidence favors no conclusion.
This is a jumble, and people will Rorschach the heck out of anything they want to.
Also, isn't there now some evidence that getting a flu vaccine every year actually reduces efficacy, and that it's only going to have its maximal (a dismal 40% or so?) effectiveness if it's administered only once every 3 - 5 years? If that's the case, and it were actually true that it was beneficial as hoped for in the IAMI study, what would you do with the patient that had their flu vaccine in the previous few years and an MI the next?
In my nonprofessional opinion flu vaccines are garbage products that no one should get in any scenario. There is definitely a lot of literature on the deleterious nonspecific effects of flu vaccines. In other words, they may increase your risk of getting other kinds of infections. I believe that - and possibly some other uncertain harms - are equalling out or outweighing any specific benefit flu vaccines have for the flu. And there is very little evidence on what happens if you get vaccinated multiple season in a row, but what is out there suggests you may be at increased risk even of the flu...