There are few more accepted practices in cardiology than giving beta-blockers after myocardial infarction. The supporting evidence, however, made me stop and think.
I really2 hope that you will do one articles addressing coapt trial vis a vis TEER. I know you write about these awhile ago but it was brief and I still cant convince my cost constrained hospital to be wary about the effectiveness.
the main reason for the popularity of metoprolol (in particular) early in acute MI was a large Swedish study done in the late seventies, I believe, and not ISIS or BATH. I remember the presentation at one of the big cardiology meetings then, but I cannot remember the authors or the publication.
Did a journal club on this meta-analyses of beta blockers trials pre/post reperfusion era back in 2016. Not sure why this didn't get more attention back then. https://pubmed.ncbi.nlm.nih.gov/24927909/
Entrenched policies and recommendations create positive feedback. In many cases, the best remaining "evidence" for many questionable policies is "That's how it's always been done!"
In many cases, the longer any policy goes unquestioned because "the science has long since been settled," the more that policy should be questioned.
I have never been a big fan of the term "statistically significant" and I think the two studies listed in this article justify that skepticism. The second one showed incidences of 3.9% and 4.6% for the drug and control groups respectively. This was followed by a statement that "the 0.7% absolute risk reduction met statistical significance". The first one showed incidences of 7% and 10.5% followed by "the 3% ARR after 2 years was highly statistically significant". This one included a graph that showed what looked like a large gap between the two lines that measured incidence of death over time. But the graph had a y axis of only zero to 14%. If placed on a graph with the y axis from zero to 100%, the two lines would appear to be almost identical. This method of deception was described in the classic text How to Lie with Statistics many years ago. The use of statistical significance certainly serves the needs of pharmaceutical companies and manufacturers of medical devices to justify the use of their products. And I am sure that researchers in need of published articles in order to advance their careers find it useful. But as a criterion for clinical decision making, it is of little, if any, use.
Beyond the specifics of the beta blocker story, this challenges the concept of “settled science” altogether. Maybe we should re-examine all sacred cows to see what may no longer apply, or be relevant to current practice.
In particular, recent trials (esp in HF) always “add on” to background therapy, which contributes to the continual March towards polypharmacy. Perhaps we also need to consider when we can reduce regimens, esp those that involve routine or multi drug combos.
My dad was put on statins and beta blockers after a stroke and about five years later developed lymphodema in the feet and a marked slowdown in his strength and movement ability. Been wondering if it was the medicine? His doctor just cut both down but stopped short of saying it was the cause.
Very good topic. The “open artery theory” emerged in the late 80’ proposing the dominant cause of death and morbidity in acute myocardial infarction was the persistent occlusion of the culprit artery. It was tested and confirmed by the early thrombolysis studies (ISIS-2, etc). Once a patient has the artery opened, all other treatments became marginal interventions, with little effect on mortality. Hence, B-blockers value as an additional therapy has to be tested again in the reperfusion era. (I think they were!)
I too appreciate this concise critical analysis. A propos of the comment regarding trials in psychiatry, our academic group at the University of British Columbia has analyzed over the years many trials at www.ti.ubc.ca. Some of our conclusions have been published in open access Therapeutics Letters at the same website (search by drug name). Very few are run independently of industry, and many are obviously "ghost-authored." Although this can seldom be proven, it's easy to get a quick idea by looking carefully at the acknowledgements, just above the reference sections of publications of trial "results." Outright fraudulent reporting may be more common than we know. (See artlcles about Study 329 of paroxetine). A key issue is how the outcomes typically measured in psychiatric trials compare with those sought by patients with mental illness or by clinicians - let alone how long to treat, long-term beneficial or adverse effects of drug treatment, or % achieving "meaningful" improvement. Selection of patients for trials and adjudication of outcomes are also important issues.
Actually we are looking again at whether there is any evidence to favour escitalopram (single enantiomer) over citalopram (racemic mixture). If any readers of Sensible Medicine have specialized knowledge in this area, I would welcome contact and/or references (DOI) via the UBC Therapeutics Initiative website (see "Send us a message" under Contact at www.ti.ubc.ca).
Tom Perry MD, FRCPC (UBC Therapeutics Initiative, Vancouver, Canada)
These new trials will be hard to be compared with the old ones due to diference in protocols, patients characteristics and the way patients are treated after acute MI. The results of betablocker therapy may not apply after the reperfusion era. The results of BHAT and Isis were very interesting in an era when knowledge of pathophysiology of MI was less than we know today. For sure, many trial results have to be rechalenged today.
It is not just heart disease. Beta blockers are also a poor choice in hypertension. There is little evidence that they lower the risk of heart attack or stroke in that setting. If you compare a year of treatment of high blood pressure with atenolol vs losartan, the artery becomes more normal with losartan and does not change with atenolol. Beta blocker treatment may be associate with weight gain, increased insulin resistance and diabetes. Not a good choice unless there is an indication for rate control etc.
I really2 hope that you will do one articles addressing coapt trial vis a vis TEER. I know you write about these awhile ago but it was brief and I still cant convince my cost constrained hospital to be wary about the effectiveness.
the main reason for the popularity of metoprolol (in particular) early in acute MI was a large Swedish study done in the late seventies, I believe, and not ISIS or BATH. I remember the presentation at one of the big cardiology meetings then, but I cannot remember the authors or the publication.
Did a journal club on this meta-analyses of beta blockers trials pre/post reperfusion era back in 2016. Not sure why this didn't get more attention back then. https://pubmed.ncbi.nlm.nih.gov/24927909/
Entrenched policies and recommendations create positive feedback. In many cases, the best remaining "evidence" for many questionable policies is "That's how it's always been done!"
In many cases, the longer any policy goes unquestioned because "the science has long since been settled," the more that policy should be questioned.
I have never been a big fan of the term "statistically significant" and I think the two studies listed in this article justify that skepticism. The second one showed incidences of 3.9% and 4.6% for the drug and control groups respectively. This was followed by a statement that "the 0.7% absolute risk reduction met statistical significance". The first one showed incidences of 7% and 10.5% followed by "the 3% ARR after 2 years was highly statistically significant". This one included a graph that showed what looked like a large gap between the two lines that measured incidence of death over time. But the graph had a y axis of only zero to 14%. If placed on a graph with the y axis from zero to 100%, the two lines would appear to be almost identical. This method of deception was described in the classic text How to Lie with Statistics many years ago. The use of statistical significance certainly serves the needs of pharmaceutical companies and manufacturers of medical devices to justify the use of their products. And I am sure that researchers in need of published articles in order to advance their careers find it useful. But as a criterion for clinical decision making, it is of little, if any, use.
Having hypertension and an ascending aortic aneurysm I have been prescribed two beta blockers.
As far as I knew there was no direct evidence that beta blockers help with aneurysms. Is that still the case?
Beyond the specifics of the beta blocker story, this challenges the concept of “settled science” altogether. Maybe we should re-examine all sacred cows to see what may no longer apply, or be relevant to current practice.
In particular, recent trials (esp in HF) always “add on” to background therapy, which contributes to the continual March towards polypharmacy. Perhaps we also need to consider when we can reduce regimens, esp those that involve routine or multi drug combos.
My dad was put on statins and beta blockers after a stroke and about five years later developed lymphodema in the feet and a marked slowdown in his strength and movement ability. Been wondering if it was the medicine? His doctor just cut both down but stopped short of saying it was the cause.
Very good topic. The “open artery theory” emerged in the late 80’ proposing the dominant cause of death and morbidity in acute myocardial infarction was the persistent occlusion of the culprit artery. It was tested and confirmed by the early thrombolysis studies (ISIS-2, etc). Once a patient has the artery opened, all other treatments became marginal interventions, with little effect on mortality. Hence, B-blockers value as an additional therapy has to be tested again in the reperfusion era. (I think they were!)
On marginalism:
https://doi.org/10.17267/2675-021Xevidence.2022.e4722
Thank you.
I mean the story is incomplete.
The story in complete without mentioning the studies of IV Metoprolol in STEMI. Please analyze them critically and write them.
I too appreciate this concise critical analysis. A propos of the comment regarding trials in psychiatry, our academic group at the University of British Columbia has analyzed over the years many trials at www.ti.ubc.ca. Some of our conclusions have been published in open access Therapeutics Letters at the same website (search by drug name). Very few are run independently of industry, and many are obviously "ghost-authored." Although this can seldom be proven, it's easy to get a quick idea by looking carefully at the acknowledgements, just above the reference sections of publications of trial "results." Outright fraudulent reporting may be more common than we know. (See artlcles about Study 329 of paroxetine). A key issue is how the outcomes typically measured in psychiatric trials compare with those sought by patients with mental illness or by clinicians - let alone how long to treat, long-term beneficial or adverse effects of drug treatment, or % achieving "meaningful" improvement. Selection of patients for trials and adjudication of outcomes are also important issues.
Actually we are looking again at whether there is any evidence to favour escitalopram (single enantiomer) over citalopram (racemic mixture). If any readers of Sensible Medicine have specialized knowledge in this area, I would welcome contact and/or references (DOI) via the UBC Therapeutics Initiative website (see "Send us a message" under Contact at www.ti.ubc.ca).
Tom Perry MD, FRCPC (UBC Therapeutics Initiative, Vancouver, Canada)
These new trials will be hard to be compared with the old ones due to diference in protocols, patients characteristics and the way patients are treated after acute MI. The results of betablocker therapy may not apply after the reperfusion era. The results of BHAT and Isis were very interesting in an era when knowledge of pathophysiology of MI was less than we know today. For sure, many trial results have to be rechalenged today.
It is not just heart disease. Beta blockers are also a poor choice in hypertension. There is little evidence that they lower the risk of heart attack or stroke in that setting. If you compare a year of treatment of high blood pressure with atenolol vs losartan, the artery becomes more normal with losartan and does not change with atenolol. Beta blocker treatment may be associate with weight gain, increased insulin resistance and diabetes. Not a good choice unless there is an indication for rate control etc.
https://pubmed.ncbi.nlm.nih.gov/14553968/
Is anyone doing what you are doing with seminal trials in psychiatry?