Cardiology PA… what an amazing breakdown! Makes you really question the current orthodoxy in the field of Cardiology. Wouldn’t be the first time and certainly won’t be the last.
Thank you so much for this videos Dr. Prasad, they are extremely interesting and useful for the medical community, if possible I think it would be of great interest to a much wider audience to hear your take on some landmark trials on internal medicine topics, such as this one. Keep up the great work on this TH-cam channel!
My dad was taking standard meds for his class I CHF but a recent episode of peripheral edema (due to him stopping his meds since he said he felt very well) they changed him to Entresto thinking this med was the long awaited ‘game changer’. I didn’t have a problem with this but wasn’t sure if his class I (asymptomatic) CHF warranted it since he was doing fine (walking 3 miles a day and all normal activities). If he moves to Class 2-5 CHF then maybe it might be warranted. However with the Entresto his kidneys immediately took a hit plus the constant worry of Hyperkalemia. Yesterday I’ve convinced his doctor to go back to his old meds and I’m praying they work as well as they did before and his kidneys can recover. This is a brilliant video Dr Prasad.
@@westfield90 Save for naturetic peptide, there isn't much difference between trusto and valsartan. The comparison group (IMT) also included people on ACEi (WTF??) so who knows if it was only people on valsartan they might have shown much better than trusto. I mean, these are people they've found don't tolerate ACEi aren't they? look at it and tell me if I'm wrong, more people bought the farm on trusto it looks like. Then there's the LIFE study, which shows no diff in a direct comparison to valsartan.
Really interesting, in my cardio block last year in Med school, we were told ARNIs were the best first line treatment based on this trial, I should have looked closer into it.
it's a marketing gimmick, there are no other ARNIs as in plural, etc etc, only one. in fact, who else is neprilysin inhibiting? please, other companies are all over these things with mee toos if there's anything to it. check out the PARALLAX trial
thank you so much for your do diligence with genuine care. I was prescribed Entresto after my EF went from 42 down to 38. I have the med. on hand but am most sceptical based on the review of the literature and pt's. experience who are 50% (-) and 39% (+). Way to go and Thanks again.
It's important to understand the problem is this thing they've added to an ARB, that doesn't really do anything, which makes it silly to pay so much. ARB are still a valid HF med, there are 8 of them, losartan is on the WHO essential meds list.
I am a Hospitalist trying to get more facile in understanding trial design and this discussion is very helpful. What a convoluted unnecessary design! Why? You gotta wonder🤔
look at Dr Poses blog post about it, then check out the trial where LCZ696 is compared to generic valsartan, they tainted the pool with people who took enalapril and valsartaan still beat out enesto. Why are doctors so easily deceived by the marketing?
Always love your videos Vinay! Also enjoyed your back and forth with Milton packer years back, we need more thoughtful critics like yourself in academia. I totally agree with most of the major limitations you point out, especially the ridiculous run-in period. Would like to see a confirmatory study as well, but I hope to provide some answers to the questions you ask in the video. Enalapril dosing: I believe Entresto 97/103 BID did in-fact outperform the standard of care (enalapril 10mg BID). I agree that those who were on higher enalapril dose should've been allowed to continue, esp since some pts in practice have underlying HTN and require the higher dosing. But the only HF trial to ever use the FDA max of 20mg BID was CONSENSUS back in 1987 and studied a completely different population than paradigm (class IV, only on digoxin and diuretic as background). The subsequent trials such as SOLVD and CARMEN utilized 10 mg BID as their target dose which became the standard. This was also reflected in the average doses in future HF trials like VAL-HEFT and MERIT-HF. The LIFE trial with entresto on the other hand probably should have used 20mg enalapril as the comparator A+B vs C design: The FDA required bidil to have the confirmatory AHEFT study not because it was A+B vs C, but because they were asked to approve the indication for black patients from post hoc analyses of V-HeFT I and II (whether there’s even any benefit Entresto in black patients is a whole separate issue on it’s own) . So yes A+B vs C is unique, but if they didn't have a crazy run-in period, this design would've been ok. I think a trial today if they compared a new patented low dose GDMT polypill (A+B+C+D) vs max dose A would be helpful Data for sacubitril monotherapy: I don’t think studying the independent contribution of sacubitril is necessary before prescribing entresto. Bactrim comes to mind as we don’t need to know the sulfamethoxazole monotherapy contribution data before it. Entresto is also a separate co-crystal compound which is the patent extender, not Sacubitril alone, since entresto isn't a traditional combined formulation.
who cares about ARB to ACEi comparisons? what is this? a public service announcement? Are doctors really that clueless they could give out ARB instead of ACEi for HF? the real question is answered in the PARALLAX trial, it's nonsense, go home, prescribe a generic ARB and stop wasting people's money.
Congratulations! Completely agree with your thoughts! In the last weeks I´ve been doing a celebrity dead match between ACEi (Veheft II, Consensus I, Solvd Treatment, Solvd Prevention, Save, Aire, Trace, Smile, Isis 4, Gissi 3, CCS 1, Cibis 3) and the ARNi wrestlers (PARADIGM, PARAGON, PARADISE, PARAGLIDE, PIONEER, STRONG HF), BUT only a few want to listen. Sadly evidence based medicine is used very often as a domination tool rahter than a knowledge one. A huge difference with other sciences (Physics, Chemestry). Why the medical community is so soft and the analysis is so weak ? Why don´t we study scientific method?, and philosophy? I´m still using ACEi in Hf patients.
Because the FDA called it a breakthru, they're a poorly funded gov agency but people believe they have magical powers to see through pharma crafty scientists and high paid lawyers. I first made that nonsense when I worked on the third floor at 100 tech square. Their labs were backwards and behind the times. I had to report them to OSHA for making us dispense our fume hood reaction waste OUTSIDE the fume hood
Why did they include people taking an ACEi in the parallax trial? Didn't they already know people who didn't tolerate ACEi would not do as well, it's just tainting the data, why didn't they compare to just valsartan? huh?
These researchers have sold their souls for money. Sometimes I wonder how they live with themselves especially when their own family members have health issues that potentially could have been helped with good research.
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Cardiology PA… what an amazing breakdown! Makes you really question the current orthodoxy in the field of Cardiology. Wouldn’t be the first time and certainly won’t be the last.
Thank you so much for this videos Dr. Prasad, they are extremely interesting and useful for the medical community, if possible I think it would be of great interest to a much wider audience to hear your take on some landmark trials on internal medicine topics, such as this one. Keep up the great work on this TH-cam channel!
My dad was taking standard meds for his class I CHF but a recent episode of peripheral edema (due to him stopping his meds since he said he felt very well) they changed him to Entresto thinking this med was the long awaited ‘game changer’. I didn’t have a problem with this but wasn’t sure if his class I (asymptomatic) CHF warranted it since he was doing fine (walking 3 miles a day and all normal activities). If he moves to Class 2-5 CHF then maybe it might be warranted. However with the Entresto his kidneys immediately took a hit plus the constant worry of Hyperkalemia. Yesterday I’ve convinced his doctor to go back to his old meds and I’m praying they work as well as they did before and his kidneys can recover. This is a brilliant video Dr Prasad.
take a look at the recent PARALLAX trial
@@FourthWayRanch can you summarize it
@@westfield90 Save for naturetic peptide, there isn't much difference between trusto and valsartan. The comparison group (IMT) also included people on ACEi (WTF??) so who knows if it was only people on valsartan they might have shown much better than trusto. I mean, these are people they've found don't tolerate ACEi aren't they?
look at it and tell me if I'm wrong, more people bought the farm on trusto it looks like.
Then there's the LIFE study, which shows no diff in a direct comparison to valsartan.
Really interesting, in my cardio block last year in Med school, we were told ARNIs were the best first line treatment based on this trial, I should have looked closer into it.
it's a marketing gimmick, there are no other ARNIs as in plural, etc etc, only one. in fact, who else is neprilysin inhibiting? please, other companies are all over these things with mee toos if there's anything to it.
check out the PARALLAX trial
thank you so much for your do diligence with genuine care. I was prescribed Entresto after my EF went from 42 down to 38. I have the med. on hand but am most sceptical based on the review of the literature and pt's. experience who are 50% (-) and 39% (+). Way to go and Thanks again.
It's important to understand the problem is this thing they've added to an ARB, that doesn't really do anything, which makes it silly to pay so much.
ARB are still a valid HF med, there are 8 of them, losartan is on the WHO essential meds list.
VP, you have a higher purpose. Someday we'll talk about this.
beautiful.
-jc
I am a Hospitalist trying to get more facile in understanding trial design and this discussion is very helpful. What a convoluted unnecessary design! Why? You gotta wonder🤔
look at Dr Poses blog post about it, then check out the trial where LCZ696 is compared to generic valsartan, they tainted the pool with people who took enalapril and valsartaan still beat out enesto. Why are doctors so easily deceived by the marketing?
Always love your videos Vinay! Also enjoyed your back and forth with Milton packer years back, we need more thoughtful critics like yourself in academia. I totally agree with most of the major limitations you point out, especially the ridiculous run-in period. Would like to see a confirmatory study as well, but I hope to provide some answers to the questions you ask in the video.
Enalapril dosing:
I believe Entresto 97/103 BID did in-fact outperform the standard of care (enalapril 10mg BID). I agree that those who were on higher enalapril dose should've been allowed to continue, esp since some pts in practice have underlying HTN and require the higher dosing. But the only HF trial to ever use the FDA max of 20mg BID was CONSENSUS back in 1987 and studied a completely different population than paradigm (class IV, only on digoxin and diuretic as background). The subsequent trials such as SOLVD and CARMEN utilized 10 mg BID as their target dose which became the standard. This was also reflected in the average doses in future HF trials like VAL-HEFT and MERIT-HF. The LIFE trial with entresto on the other hand probably should have used 20mg enalapril as the comparator
A+B vs C design:
The FDA required bidil to have the confirmatory AHEFT study not because it was A+B vs C, but because they were asked to approve the indication for black patients from post hoc analyses of V-HeFT I and II (whether there’s even any benefit Entresto in black patients is a whole separate issue on it’s own) . So yes A+B vs C is unique, but if they didn't have a crazy run-in period, this design would've been ok. I think a trial today if they compared a new patented low dose GDMT polypill (A+B+C+D) vs max dose A would be helpful
Data for sacubitril monotherapy:
I don’t think studying the independent contribution of sacubitril is necessary before prescribing entresto. Bactrim comes to mind as we don’t need to know the sulfamethoxazole monotherapy contribution data before it. Entresto is also a separate co-crystal compound which is the patent extender, not Sacubitril alone, since entresto isn't a traditional combined formulation.
who cares about ARB to ACEi comparisons? what is this? a public service announcement? Are doctors really that clueless they could give out ARB instead of ACEi for HF?
the real question is answered in the PARALLAX trial, it's nonsense, go home, prescribe a generic ARB and stop wasting people's money.
look at the HFN-LIFE study.
thank you for the honest scrutiny
Excellent talk. Thanks. I do not prescribe entresto.
Congratulations! Completely agree with your thoughts! In the last weeks I´ve been doing a celebrity dead match between ACEi (Veheft II, Consensus I, Solvd Treatment, Solvd Prevention, Save, Aire, Trace, Smile, Isis 4, Gissi 3, CCS 1, Cibis 3) and the ARNi wrestlers (PARADIGM, PARAGON, PARADISE, PARAGLIDE, PIONEER, STRONG HF), BUT only a few want to listen. Sadly evidence based medicine is used very often as a domination tool rahter than a knowledge one.
A huge difference with other sciences (Physics, Chemestry).
Why the medical community is so soft and the analysis is so weak ?
Why don´t we study scientific method?, and philosophy?
I´m still using ACEi in Hf patients.
WHY DO YOU TALK SO FUCKING FAST?
Because the FDA called it a breakthru, they're a poorly funded gov agency but people believe they have magical powers to see through pharma crafty scientists and high paid lawyers. I first made that nonsense when I worked on the third floor at 100 tech square. Their labs were backwards and behind the times. I had to report them to OSHA for making us dispense our fume hood reaction waste OUTSIDE the fume hood
I had to stop. I was feeling better, but my psycho, Dr. Decided to change my meds. BP crashed and pulse raced.
Why did they include people taking an ACEi in the parallax trial? Didn't they already know people who didn't tolerate ACEi would not do as well, it's just tainting the data, why didn't they compare to just valsartan? huh?
Ya man do more IM videos
You are a smart guy with a lot to share! HOWEVER, YOU TALK TOO FAST, WAY TOO FAST!!
You can slow the speed down in the settings (gear lower right corner).
These researchers have sold their souls for money. Sometimes I wonder how they live with themselves especially when their own family members have health issues that potentially could have been helped with good research.