Thank you Dr Prasad You are the only physician to confirm what I have done for years only to be told by I am wrong by my overseers I have for years just up titrated ACE inhibitors in CHF (most actually improved EF on that) before Entresto
I have also made myself persona non grata at lectures by asking these kinds of patient-centered, real-world questions. The big (not so big?) Entresto trial showed an NNT of 24 for the primary (combined) outcome and 36 for all cause mortality over the course of the (prematurely stopped) trial of this extremely expensive new drug. But a further look into the numbers showed that around 50% of the cohort was not on spironolactone, a very cheap guideline-recommended drug that has a NNT of around 9. How can anyone claim victory for any long-term outcomes with these kinds of issues (not to mention several others).
A followup study, btw, reinterpreted (and extrapolated) the data to get a "years needed to treat": patients could gain 1 year for every 12 years of treatment. Of course, they didn't mention that the life expectancy of a patient with stage 3 heart failure was only 5 years....
The hypothesis of early usage of “4 drugs for everyone with a pulse in HF” was tested in DAPA-ACT…and it failed to show a difference (80% + on beta blocker, 70%+ on RAAS blocker, and about 50% on MRA, to which Dapa 10 vs placebo was trialed).
Now, wait….of course there was a meta analysis to try to salvage the train wreck….in which it was combined with EMPULSE (very small trial, very short follow up, “win ratio” to obfuscate hard clinical endpoints, and difference driven by the softer stuff) and SOLOIST WHF(stopped early from loss of funding, change in primary endpoint, only diabetic pts enrolled, different class of agent SGLT 1 + SGLT2).
It is pathetic stuff that the “thought leaders” push without seemingly much thought, and probably without too much more integrity than that.
But hey, somebody has to keep the lights on at the big meetings.
I've had a problem with "guideline directed therapy" since the relatively early, heavily conflicted guidelines promoted multi-antibiotic treatment of pneumonia, based on antimicrobial sensitivities (observed somewhere, probably in Baltimore or Boston, USA). Strangely enough, the USA is not all of planet Earth. More important, those guidelines were not based on clinical results, and have since been repudiated.
About the same time, diabetes guidelines promoted drugs based on surrogate outcomes only - and those with little or no proven connection to clinically important outcomes (e.g. to blindness, amputation, kidney failure, vascular events). Looking back, is it possible that those guidelines harmed far more people than they helped?
About the time I left hospital medicine, the "sepsis guidelines" came along, advocating "goal directed therapy." I think I made a number of enemies in medical grand rounds by asking aloud why the official "goals" (central venous pressure measured invasively, mixed venous pO2, venous lactate, specific volumes of intravenous fluid replacement) were substituted for obvious goals such as mortality, length of hospital stay, complications of sepsis, etc. From what I read of clinical trials comparing the sepsis campaign guidelines with prior standard therapy, the results were no better, or possibly worse than what was done before (overresuscitation with fluid causing acute pulmonary edema, etc.)
Even less conflicted, more carefully constructive guidelines sometimes seem to rely on what the authors concede is "weak" evidence.
But an important flaw everywhere is the lack of consideration to what comes after survival. If one were able to avoid all strokes, myocardial infarctions, episodes of heart failure, or deaths from sepsis or cancer, what would come next? Who will provide the long-term care and other services to people whose deaths are delayed significantly, and who will pay for that care?
Even more important, how will such a trend compare with the lives of 6-7 billion younger people (or more) who do not presently enjoy any similar advantages, and whose lives and livelihoods are increasingly threatened by global climate change?
Reports of clinical trials that apparently succeeded in reducing total mortality during the period of study or follow-up typically speak of "preventing death." If this is indeed possible, I've yet to run across it during 75 years of life. Should any reader of Sensible Medicine know of an academic medical journal article that even mentions this conundrum, I'd be most interested to see the reference posted n a response here at Sensible Medicine.
Tom Perry MD, FRCPC (retired Canadian general internist)
The patient isn't even convinced they need to be on meds. Their 10-minute appt left them with more questions than answers. Suddenly they're looking at themselves in the mirror popping 4 unknown pills, wondering why they feel terrible, have a headache, and an upset stomach. This is not the way to gain their trust. It's trying to be perfect out of the gate instead of gradually escalating the treatment, titrating to the patient's faith in getting better.
"If patients had skin in the game and had to use their own money, we would have a slew of third parties evaluating this evidence, skeptically and making prudent recommendations." So this should be a testable hypothesis, how would you design a study to test this? Because there will always be people selling snake oil, and there is a vast assymetry of information. Would prudent recommendations be followed? And you know how conflicted are many of those making these "prudent" recommendations.
In an analagous situation, how many people rely on guides such as consumer reports for their "skin in the game" consumer purchases?
In the real world, people go bankrupt dealing with their copay, let alone the whole amount, so they already do have some skin in the game.
Thank you Dr Prasad You are the only physician to confirm what I have done for years only to be told by I am wrong by my overseers I have for years just up titrated ACE inhibitors in CHF (most actually improved EF on that) before Entresto
I have also made myself persona non grata at lectures by asking these kinds of patient-centered, real-world questions. The big (not so big?) Entresto trial showed an NNT of 24 for the primary (combined) outcome and 36 for all cause mortality over the course of the (prematurely stopped) trial of this extremely expensive new drug. But a further look into the numbers showed that around 50% of the cohort was not on spironolactone, a very cheap guideline-recommended drug that has a NNT of around 9. How can anyone claim victory for any long-term outcomes with these kinds of issues (not to mention several others).
A followup study, btw, reinterpreted (and extrapolated) the data to get a "years needed to treat": patients could gain 1 year for every 12 years of treatment. Of course, they didn't mention that the life expectancy of a patient with stage 3 heart failure was only 5 years....
The hypothesis of early usage of “4 drugs for everyone with a pulse in HF” was tested in DAPA-ACT…and it failed to show a difference (80% + on beta blocker, 70%+ on RAAS blocker, and about 50% on MRA, to which Dapa 10 vs placebo was trialed).
Now, wait….of course there was a meta analysis to try to salvage the train wreck….in which it was combined with EMPULSE (very small trial, very short follow up, “win ratio” to obfuscate hard clinical endpoints, and difference driven by the softer stuff) and SOLOIST WHF(stopped early from loss of funding, change in primary endpoint, only diabetic pts enrolled, different class of agent SGLT 1 + SGLT2).
It is pathetic stuff that the “thought leaders” push without seemingly much thought, and probably without too much more integrity than that.
But hey, somebody has to keep the lights on at the big meetings.
I've had a problem with "guideline directed therapy" since the relatively early, heavily conflicted guidelines promoted multi-antibiotic treatment of pneumonia, based on antimicrobial sensitivities (observed somewhere, probably in Baltimore or Boston, USA). Strangely enough, the USA is not all of planet Earth. More important, those guidelines were not based on clinical results, and have since been repudiated.
About the same time, diabetes guidelines promoted drugs based on surrogate outcomes only - and those with little or no proven connection to clinically important outcomes (e.g. to blindness, amputation, kidney failure, vascular events). Looking back, is it possible that those guidelines harmed far more people than they helped?
About the time I left hospital medicine, the "sepsis guidelines" came along, advocating "goal directed therapy." I think I made a number of enemies in medical grand rounds by asking aloud why the official "goals" (central venous pressure measured invasively, mixed venous pO2, venous lactate, specific volumes of intravenous fluid replacement) were substituted for obvious goals such as mortality, length of hospital stay, complications of sepsis, etc. From what I read of clinical trials comparing the sepsis campaign guidelines with prior standard therapy, the results were no better, or possibly worse than what was done before (overresuscitation with fluid causing acute pulmonary edema, etc.)
Even less conflicted, more carefully constructive guidelines sometimes seem to rely on what the authors concede is "weak" evidence.
But an important flaw everywhere is the lack of consideration to what comes after survival. If one were able to avoid all strokes, myocardial infarctions, episodes of heart failure, or deaths from sepsis or cancer, what would come next? Who will provide the long-term care and other services to people whose deaths are delayed significantly, and who will pay for that care?
Even more important, how will such a trend compare with the lives of 6-7 billion younger people (or more) who do not presently enjoy any similar advantages, and whose lives and livelihoods are increasingly threatened by global climate change?
Reports of clinical trials that apparently succeeded in reducing total mortality during the period of study or follow-up typically speak of "preventing death." If this is indeed possible, I've yet to run across it during 75 years of life. Should any reader of Sensible Medicine know of an academic medical journal article that even mentions this conundrum, I'd be most interested to see the reference posted n a response here at Sensible Medicine.
Tom Perry MD, FRCPC (retired Canadian general internist)
"Bizarre idea" indeed. Sounds like something generated at cocktail hour by pharmaceutical salesmen.
The patient isn't even convinced they need to be on meds. Their 10-minute appt left them with more questions than answers. Suddenly they're looking at themselves in the mirror popping 4 unknown pills, wondering why they feel terrible, have a headache, and an upset stomach. This is not the way to gain their trust. It's trying to be perfect out of the gate instead of gradually escalating the treatment, titrating to the patient's faith in getting better.
More like 7-8 new pills: aspirin/ potassium/diuretic/probably GERD med??
So true - this piece speaks to 'sensible medicine', & indeed, illustrates the necessity for 'personalised' (for this patient at this time) medicine
I'm totally with you on most of this. Except:
"If patients had skin in the game and had to use their own money, we would have a slew of third parties evaluating this evidence, skeptically and making prudent recommendations." So this should be a testable hypothesis, how would you design a study to test this? Because there will always be people selling snake oil, and there is a vast assymetry of information. Would prudent recommendations be followed? And you know how conflicted are many of those making these "prudent" recommendations.
In an analagous situation, how many people rely on guides such as consumer reports for their "skin in the game" consumer purchases?
In the real world, people go bankrupt dealing with their copay, let alone the whole amount, so they already do have some skin in the game.