The polypill consideration is interesting. I don't quite understand why we'd compare "polypill" to "placebo". In all honesty, I did not understand the point of the paper or really, the review here. "placebo" being "standard care" - which includes antihypertensive treatment (?) So, whatever else they were doing to control BP and adding the "triple pill". Or why we are interested in how Sri Lankans do after ICH? This entire discussion is oddly niche.
What I'm interested in: does combo therapy get us to goal more rapidly or more effectively than single agent therapy and I can tell you from experience that it does. Is polypill therapy better for compliance than comparable combo therapy all in separate pills? That I don't know, but would think that it is.
It pained me when my BIL with a BP of 200/95 was started on Losartan 50 mg and the process started there. I don't think this is uncommon. How much more efficient and effective is combo pill therapy - starting olmesartan-amlodipine combo? Absolutely.
Seeing a new patient on a list of 5 antihypertensives (including minoxidil) and recognizing that he was not taken many or most of those was helpful. Hearing from him that he doesn't want to "take pills all day long" led to finding the best combo pill available (combo 2 antihypertensives and a statin) - compliance (and blood pressure!) drastically improved. Not asking your patient what he's really doing and what things are creating obstacles and just throwing pill after pill into the mix - useless. Knowing your patient and discussing what issues might limit their compliance - priceless.
It was known early on that Paxlovid was not indicated for vaccinated people - that there was no benefit for Paxlovid and there were side effects, rebound, and drug-drug interactions (I guess I paid attention to Prasad's analysis and review). Along with the basic data, any of us in the practice of medicine at this time saw that Covid had morphed into a lower risk illness and that those taking Paxlovid vs not were all doing as well.
The interesting things that happened: quite early on during Covid pandemic, I received a letter from CMS encouraging me to accept boxes of Paxlovid to keep in my office and hand out to patients - which I declined. But was interesting that US healthcare wanted me to have it (could it have been the government had paid for many many boxes of Paxlovid and needed something to do with it?)
The main issue that played a role in the entire Paxlovid issue: human nature wanting to "do something" when sick. Patients with that mindset want to take something when ill - that mindset is not highly interested in "data". Many doctors have similar mindset. That drove a significant degree of paxlovid prescribing (and still does). Very similar to the Tamiflu predicament.
I’m happy to have the results of the Paxlovid study, however belated. I’ve been in a slight minority amongst my colleagues unwilling to prescribe it for vaccinated patients (so many drug interactions and rebound symptoms) primarily because we haven’t really had a good study on that patient population. I’m so glad it’s done.
Another brilliant and important discussion, thank you. I would add that the use of observational data, particularly bad, retrospective data, as Dr. Cifu points out, was rampant in mass media outlets that wanted the drug to work. They consistently ignored trials, and deferred to bad observational data, often on the say so or advice of ‘experts’. This reveals how medical and anatomic expertise is so often divorced from evidence expertise. An unfortunate chapter. Let’s hope you shining a light on this will make that much more difficult in the future. Wonderful work!
The first time I saw a paxlovid, commercial and realized the name was designed to rhyme with COVID, I cringed and immediately assumed it was probably useless just based on the commercial 😁
Generic polypill question: A polypill is more convenient than taking three separate drugs and as Dr. Foy pointed out, there may be some benefit synergistically in having them all together. however, how do you titrate a polypill sincec, going up, or down affects all 3 drugs and you can't just tweak one or two? Also, how do you know which drug is causing the potential unpleasant side effects and is there an increased risk when the drugs are together instead of separate?
This is the problem w polypills. There are a few meds we commonly get in combo and it's a nuisance to titrate. The most annoying is lisinopril/hctz (2 blood pressure meds). The combo pill does not come in a dose that maxes out the lisinopril component so one ends up doing stuff like having patients take the combo pill plus lisinopril 20mg. It's not confusing at all...
Thanks, this was a great discussion. I had many friends take Paxlovid. I gave them the information about its ineffectiveness. Many experienced the "Rebound". The response to COVID was so hard to watch and experience. The 30 day follow-up answered their primary endpoint question. Could there have been side effects from the drug that arose after 30 days?
The polypill consideration is interesting. I don't quite understand why we'd compare "polypill" to "placebo". In all honesty, I did not understand the point of the paper or really, the review here. "placebo" being "standard care" - which includes antihypertensive treatment (?) So, whatever else they were doing to control BP and adding the "triple pill". Or why we are interested in how Sri Lankans do after ICH? This entire discussion is oddly niche.
What I'm interested in: does combo therapy get us to goal more rapidly or more effectively than single agent therapy and I can tell you from experience that it does. Is polypill therapy better for compliance than comparable combo therapy all in separate pills? That I don't know, but would think that it is.
It pained me when my BIL with a BP of 200/95 was started on Losartan 50 mg and the process started there. I don't think this is uncommon. How much more efficient and effective is combo pill therapy - starting olmesartan-amlodipine combo? Absolutely.
Seeing a new patient on a list of 5 antihypertensives (including minoxidil) and recognizing that he was not taken many or most of those was helpful. Hearing from him that he doesn't want to "take pills all day long" led to finding the best combo pill available (combo 2 antihypertensives and a statin) - compliance (and blood pressure!) drastically improved. Not asking your patient what he's really doing and what things are creating obstacles and just throwing pill after pill into the mix - useless. Knowing your patient and discussing what issues might limit their compliance - priceless.
It was known early on that Paxlovid was not indicated for vaccinated people - that there was no benefit for Paxlovid and there were side effects, rebound, and drug-drug interactions (I guess I paid attention to Prasad's analysis and review). Along with the basic data, any of us in the practice of medicine at this time saw that Covid had morphed into a lower risk illness and that those taking Paxlovid vs not were all doing as well.
The interesting things that happened: quite early on during Covid pandemic, I received a letter from CMS encouraging me to accept boxes of Paxlovid to keep in my office and hand out to patients - which I declined. But was interesting that US healthcare wanted me to have it (could it have been the government had paid for many many boxes of Paxlovid and needed something to do with it?)
The main issue that played a role in the entire Paxlovid issue: human nature wanting to "do something" when sick. Patients with that mindset want to take something when ill - that mindset is not highly interested in "data". Many doctors have similar mindset. That drove a significant degree of paxlovid prescribing (and still does). Very similar to the Tamiflu predicament.
I’m happy to have the results of the Paxlovid study, however belated. I’ve been in a slight minority amongst my colleagues unwilling to prescribe it for vaccinated patients (so many drug interactions and rebound symptoms) primarily because we haven’t really had a good study on that patient population. I’m so glad it’s done.
Another brilliant and important discussion, thank you. I would add that the use of observational data, particularly bad, retrospective data, as Dr. Cifu points out, was rampant in mass media outlets that wanted the drug to work. They consistently ignored trials, and deferred to bad observational data, often on the say so or advice of ‘experts’. This reveals how medical and anatomic expertise is so often divorced from evidence expertise. An unfortunate chapter. Let’s hope you shining a light on this will make that much more difficult in the future. Wonderful work!
The first time I saw a paxlovid, commercial and realized the name was designed to rhyme with COVID, I cringed and immediately assumed it was probably useless just based on the commercial 😁
Generic polypill question: A polypill is more convenient than taking three separate drugs and as Dr. Foy pointed out, there may be some benefit synergistically in having them all together. however, how do you titrate a polypill sincec, going up, or down affects all 3 drugs and you can't just tweak one or two? Also, how do you know which drug is causing the potential unpleasant side effects and is there an increased risk when the drugs are together instead of separate?
This is the problem w polypills. There are a few meds we commonly get in combo and it's a nuisance to titrate. The most annoying is lisinopril/hctz (2 blood pressure meds). The combo pill does not come in a dose that maxes out the lisinopril component so one ends up doing stuff like having patients take the combo pill plus lisinopril 20mg. It's not confusing at all...
Thanks, this was a great discussion. I had many friends take Paxlovid. I gave them the information about its ineffectiveness. Many experienced the "Rebound". The response to COVID was so hard to watch and experience. The 30 day follow-up answered their primary endpoint question. Could there have been side effects from the drug that arose after 30 days?
Thanks for another helpful discussion. Was the positive result from the Paxlovid observational trials likely a placebo effect then?
Probably residual confounding.