De-intensify anti-hypertensives for nursing home residents with dementia? Athanase Benetos and Mike Steinman

Eric 00:00

Welcome to the GeriPal Podcast. This is Eric Widera.

Alex 00:03

This is Alex Smith.

Eric 00:04

And Alex, who do we have on the podcast with us today from Europe?

Alex 00:08

From France, we are delighted to welcome Athanase Benetos, who is a geriatrician researcher at the University Hospital of Nancy Lorraine and senior researcher at the National Institute of Biomedical Research in cern. Welcome to the GeriPal Podcast. Athanase.

Athanase 00:29

Hello. I’m very pleased to be with you today.

Alex 00:32

And we’re delighted to welcome back Mike Steinman, who’s a geriatrician researcher at UCSF in the Division of Geriatrics and Co PI of the US Deprescribing Research Network. Mike, welcome back to GeriPal.

Mike 00:47

Always a pleasure. Thanks.

Eric 00:48

So we’re going to be talking about one of our favorite subjects here on GeriPal, deep prescribing this time talking about deprescribing antihyd hypertensives in older adults and nursing home patients. Really important study that came out this last year was a New England journal study headed by Athanase on deprescribing antihypertensive in nursing home patients. We’re going to be talking about that and so much more. But before we do, we always have a song request. Athanase, do you have a song request for Alex?

Athanase 01:18

Yes, I propose a song that I like very much, which is Hymne A L’amour.

Eric 01:24

Why’d you pick this song?

Athanase 01:26

I think it’s very known song actually, not only in France. And while I like this song, I like very much the singer Edith Piaf, which was a great, great person and great singer and she, she wrote the lyrics.

Eric 01:47

Well, Alex likes this because he likes talking in a French accent. So we’ll see how he does.

Alex 01:53

Yeah, I don’t understand a word of this, but I love singing in French and I like trying to speak in French. So apologies to those of you who speak French. Here’s a little bit.

Alex 03:09

(singing)

Eric 03:24

Alex, it’s like I’m sitting in a cafe in the Marais.

Eric 03:29

Well done. Can you describe what’s the lyric is saying briefly?

Athanase 03:34

Well, the lyrics are very, very nice, actually. And they say globally that even if the, everything disappears, even everything is. I mean, it’s broken down is. I mean, the worst things can happen. I can accept everything City mem if you love me so. And this is a very. Yes, it’s. And what I mean was really something that extremely powerful. I mean, her voice, you know, it’s Little like that. And what. One thing, very, very important detail, this song.

I mean, she first sang this song in 1949, in September. She was, you know, in a cabaret at that time. And one month later, something like, I think, October. Her big love was a boxer, you know, Marcel Cerdon, a very known French boxer. He was her man. And he died in an accident, in a plane accident. And the night she was completely destroyed, she was. And the night she. Just one hour after she learned he died, she came out because she has to sing. And she came out and she sang this song.

Eric 05:01

Oh, wow.

Athanase 05:02

So this is something, a detail, just

Eric 05:05

the added weight to the song.

Athanase 05:07

Yeah, yeah. Marcel Serdon was, I think, a world champion in boxing.

Mike 05:14

Yeah.

Eric 05:15

Well, let’s dive into the topic at hand, deprescribing in nursing home patients. Athanase, I’d like to turn to you, like, we’ve had Mike on. On deep prescribing. I’d love to hear from you, like, what drove you to this topic of deprescribing as part of kind of the research that you’re currently doing? What was your origin story in deprescribing?

Athanase 05:38

Yeah, yeah, It’s a clinical. It’s a completely, let’s say, clinical question. Actually, I work. I mean, initially I’m cardiologist.

Mike 05:48

I.

Athanase 05:48

And then geriatrician. Okay. I mean, all the time. And I, for the moment, I have arrived in France 45 years ago. I started working mainly on hypertension and other cardiovascular diseases and other cardiovascular risk factors in Paris for many years. And at that time, you know, in. Back in the 80s, the older people were people over 60 or 65. So progressively we understood that we had to treat older people for hypertension. I mean, those with 60, 65, 70, and so on. And then progressively we had more and more older patients in our department.

And then the question was in a people with a lot of comorbidities, frailty, a lot of other medication, the question was, I was seeing the patients, and you could understand really, if it was the same thing son were doing with the other younger patients or even older patients, but not with all these problems. So the question is, and the thing is that we realized always that in the clinical research, all these people, the very old and especially the frail people with a profile of nursing homes and other frail people, were always excluded from the studies.

They were those who had the most, the biggest number of medications, cardiovascular medications, maybe cardiohypertensive medication, a lot of medication. But we’re always excluded from the clinical studies to see which are the benefits and the risk. And at the same time we start working in observational studies and we observed that those people with treated hypertension with at least more than one medication and with low systolic blood pressure less than 130 had an overmortality. But this was an observational study. We don’t know what was the cause and the consequences and, and the, and the reasons for that.

So he said there is one reason to answer these questions is to do a randomized study, which means that it’s not just I observe what happens, but I say I tried to do an intervention and to see if I can change things. Yeah. So our approach was to ask this question that nobody had, let’s say, I mean, nobody. Yeah, nobody had tried to answer in a randomized long term clinical trial. What happens in these patients if I decrease then the hypertensive treatment. Yeah. So this is the initial, and there is another point here, a more detailed let’s say, but an important detail that these kind of medication, which is cardiovascular medication, it’s very difficult for a gp, for instance, to stop, to interrupt the medication because we believe that it’s true.

Many, very often it’s true that if you stop a medication, I mean, there will be a lot of problems. So, and in this case, so instead of trying every time to understand the balance between the benefits and the risk of the treatment, to make a decision, the decision is made only saying, okay, but if I stop a medication, there will be maybe problems. So if I stop it, if there is a problem, it’s my error physician. If I don’t stop it and there is a problem, if is the disease or the medication, it’s not. See, you see, this is, it’s not a criticism I make for the other physicians. I say it’s, it’s natural in the thinking of a physician. And this is why we decided to do this interventional study. Yeah.

Eric 09:39

And Mike, I’m going to turn to you. I mean, I can think of a lot of study, I mean, Sprint’s a great, great example of a study that excluded nursing home patients. But there’s a bunch of other hypertension studies starting people on increasing lower, you know, systolic blood pressures, on blood pressure, which seems to benefit a large portion of people.

There’s not a lot of deep prescribing studies out there. How important do you think there are to do these deep prescribing studies versus just looking at the prescribing studies and saying, oh, you know what, they excluded These people, we don’t know if they benefit. Maybe we should just trial to see what happens to their blood pressure if we stop them.

Mike 10:19

So it’s actually a great question and it’s something I think about a fair amount. I think it is important. And there’s a few reasons why. You know, first of all, this is not really a scientific reason, but it’s more of a dissemination reason, is that changing clinician and patient behavior, you need studies that actually are targeted at the research question that their people are facing. And the translation that people have from taking a prescribing studies to a deprescribing context doesn’t necessarily always happen. So providing more direct evidence is useful.

But from a scientific perspective, there are actually important differences that can be useful to consider. And there is, you know, the data are limited, but there are some suggestions from other cardiovascular drugs, particularly aspirin and statins, that there are differences in clinical outcomes compared to starting the drug versus stopping the same drug. So if you take aspirin, for example, there’s been a bunch of trials that were published several years ago that showed primary prevention. Using aspirin for primary prevention of cardiovascular disease in older adults yields net harms. People are harmed more than they benefit. So a lot of guidelines basically say don’t do that.

But then they looked at those studies that inform those guidelines. And a small number of people in those studies were people who had baseline, were taking aspirin, and then they were randomized to stopping or continuing, whereas most people were not taking it. They were randomized to keep not taking it or starting. So they kind of did this really innovative thing where they looked at these people who were already taking it baseline and deprescribed it, and their outcomes were different than the people who weren’t taking it and were started it. And in fact, there was a suggestion of net benefit. If you are already taking aspirin, there’s a net benefit to continuing it in terms of the cardiovascular reduction in the bleeding risk compared to stopping it. So why could this be?

And there’s a few potential explanations. One is that once you’re already taking a drug, you’ve changed the physiologic milieu. You’ve already like up and sort of downregulated your physiologic systems. And when you stop that drug, you can change that and that can change your adverse effect outcomes. And then there’s probably also healthy survivor effects as well. Like if you start a drug and you have a bad effect, you’re going to stop it. Most likely, hopefully.

Eric 12:29

Yeah.

Mike 12:29

But the people who are, who have been taking the drug for years, they’re kind of like the healthy survivors and they are de enriched for the risk of adverse events, so. And these principles also have been suggested to play to statins as well. How they apply to antihypertensives and pretty much every other drug, we don’t know. But at least there’s some suggestion that, that there could be differences. So we do need to evaluate it empirically.

Alex 12:54

And why is it that there aren’t more deprescribing studies?

Mike 12:58

Well, deprescribing ain’t pharma.

Athanase 13:03

It’s hard.

Mike 13:03

It takes a lot of money.

Athanase 13:04

It takes a lot of money, right?

Mike 13:06

It takes a lot of money and a lot of people, and who’s gonna pay for it? So I think that’s a big, you know, plus. It’s also just been less on people’s consciousness, so hopefully that’s changing. There’s been a major uptick in deprescribing studies, but if you look at the number of prescribing studies to deprescribing studies, deeper driving is a minuscule fraction. And so it’s gonna take a while to get there.

Eric 13:29

Yeah, so we had some observational studies, you know, looking at this. So I think we alluded to the. Was a partage study which looked at people 80 years and old in a nursing home. What happens if their blood pressure’s below 130? They were on least one hypertensive medicine, and it looks like they actually did. Did worse. And there’s also, I think there’s a, a thought that. And a. Some study showing that blood pressure actually decreases. Like if you look at decedents, those who’ve died, blood pressure actually decreases in the last decade before death in older adults. Are these also the. It sounds like these are the things that kind of pushed you towards doing this study. Athanos.

Athanase 14:14

Yeah, you’re right. This is what I was saying. I mean, when we observed this over mortality in the Partash study we have, I mean, done about 10, 15 years ago, it’s impossible to answer the question why these patients have an overmotality is related to the fact that the blood pressure was very low with the medication or these people had, let’s say, other problems. And these problems needed more medications. And I mean, they have an overmortality.

And the overmortality was not the consequence of the low blood pressure, but low blood pressure was the problem, the consequence of many problems. So this is difficult to, to. To. I mean, to answer these questions, if you have only observational studies and you

Eric 15:13

decided to do a randomized control study

Athanase 15:15

in a. I mean, this did not, of course, this is not the only way to answer the question. But you, I mean, there is not only the randomized control size, there are others possibilities. But the, the, the advantage of a randomized control study is that you say, okay, I will try to keep the same conditions for the rest because I randomized these patients. And the only difference is that I remove or not the medication. I mean, this is the only difference because the follow up was exactly the same except the, the management of the anti hypertensive treatment. Yeah.

Eric 15:52

Can you briefly describe what you did in this study?

Alex 15:56

Yeah.

Athanase 15:56

So we said we will include in this study this profile of old, very old people over 80 having at least two antihypertensive medication and having also a low systolic blood pressure. As I said, just to remind that this is not only our partage study that showed, let’s say, problematic, let’s say profile of these patients, but several others observational studies. There are at least 10, 20 other observational studies. They’ve shown that people under antihypertensive medication with low systolic blood pressure, low blood pressure generally have higher morbidity and mortality. So it’s not, it was not the only one anyway. So we took this population, this.

Eric 16:48

Your low blood pressure is less than 130systolic.

Athanase 16:51

130, yes. And why nursing homes? Because we had decided to take, let’s say in the place where we have the most important percentage of frail and very frail people, which means all those people who had systematically excluded from the clinical trial so far. And so we randomize, of course people had to consent for that. This is very important. And since we decided not to exclude the most fray, we obtained from the ethical committee the authorization to have.

When a patient was not able to consent to sign the consent to have this consent from another person of, I mean, his or her family or a person of confidence, a confidence person, confident person, and so on. So under these conditions, this study had no, any exclusion, almost any exclusion criterion, when I mean any exclusion criterion means that the only exclusion criterion was if none of the antihypertensive drugs for this for a given patient, if none of these medications could be stopped due to compelling other indications, which means other concomitant diseases that for this patient needed absolutely to have this medication, for instance, a patient with a severe heart failure and who had problems of, let’s say, salpia retention and so on. And he had a diuretic for hypertension.

And for this other disease, we could not stop the diuretic in this patient. This is an example. So if none of the drugs this patient had could be stopped, he was not, she was not excreted. Okay?

Alex 18:55

Otherwise, patients who had a life expectancy of three months or less, which I think is important because our audience are people, clinicians who care for older adults and people with serious life limiting illness. So their prognosis of less than three months, they were excluded from the trial, is that right?

Athanase 19:14

Yes, but only that, I mean, because we said that, I mean, it is not for the patient doesn’t have any interest to be included in such a study. But patients with severe, let’s say dementia, patients with other severe problems, since the objective was to see reducing the treatment, deprescribing, I mean, was beneficial or had no harms, these patients were included. And this was a very important point for us. So we included, and these patients were randomized, as I said, after that, the one group, the, the interventional group, we set the physicians, the GPs of these patients, that we are going to manage the antihypertensive drugs, as I said, without other compelling indication. And for the rest of the treatment, the GPs continue to do as usually.

And in the control group, the physician could, I mean, continue to treat patients also for hypertension, as usual. And then. So one important thing is that of course we said we manage in the intervention group treatment, antihypertensive treatment. But if you as a physician, when you see your patient, you think that you have to reintroduce the treatment for any reason, you can do it, but you have to record that so we can have this information during the next visit.

Eric 20:55

So let me ask you what you actually did for the deprescribing part, because it sounds like you had a general order of deprescribing that you kind of followed, which you stop the central antihypertensive drugs first, then the loop diuretics, which all makes sense, right? Probably the least helpful from a blood pressure standpoint. Then the non dihydromen calcium channel blockers and the beta blockers. And then there’s a group where I can consider them kind of roughly equivalent arbs, aces and thiazides. And then lastly the dihydro prydrinine calcium channel blockers. How did you pick that order?

Athanase 21:32

Well, I mean, the, the scientific committee decided to do this order. So again, from the beginning, for one person, one given person, there was those antihypertensive that could be Stopped. And those who know, I explained why. So among those. And then. So he said, for this, let’s say Madame Simon, she has three medications. Okay. And from the antihypertensive among those, one cannot be stopped. And she has the two other medications. Okay. So. And then we had an order, as you said. I will not repeat the order. Why you chose that? Okay, because in European guidelines, in national but also international guidelines, let’s say the calcium channel brokers, converting enzyme inhibitors and thiazides, the one part of diuretic methyzides, are considered as the most used medications.

The first line for the older people. There is a big debate for beta blockers. Most countries put those medication in second on third line for older people. And so we said. Which are. So we try to make based on the different guidelines throughout. I mean, this last, let’s say 20 years, the order we fixed was the kind of logical order. It’s not a guideline, but I think it’s something that it’s logical. For instance, the central medications, like old medication like methyl dopa or clonidine are not. Not very used in older people now, but there are still some and we know that the side effects are very important. So he said this would be the first we will stop and so on.

Eric 23:28

Mike, how you feeling about that order?

Mike 23:30

No, it totally makes sense to me. I mean, both because it adheres to guidelines about, you know, which suggests the evidence of effectiveness, but also in older adults, like, the main thing we’re trying to avoid is harms. Not the only thing, but a main thing. And certainly if I had a choice of giving someone a, you know, amlodipine or a non di. Non dihydropyridine calcium channel blocker or giving them a loop diuretic, which is more likely to cause side effects. Like I know which one I’m choosing. So the ones that have the best antihypertensive effect, but honestly, the ones that are least likely to cause harms are the ones that we should be keeping on preferentially.

Athanase 24:03

All right. Yes. And as you. As you have seen, the loop diuretics were very. One of the first after the central. And the alpha blockers, the loop diuretics, they made towards the third to stop. And since most of the very few patients has alpha blockers on or central, most of the time, the first medication was looked diuretic.

Alex 24:25

Yeah.

Eric 24:26

So maybe we’ll decrease the suspense for everybody. What did you find?

Athanase 24:31

Well, we found that there was no. In the. We put this as the main criterion, the total mortality yeah, big discussion on that because many people say, okay, but in older people the most important is not if you die or how you die and what’s the quality of life and so on. But we said for two reasons, we put the general total mortality as a first criterion. Because first, I mean, there is no discussion about if this endpoint is yes or no.

Eric 25:02

I mean this is like, you know, mortality.

Athanase 25:06

It’s a very hard criteria, it’s important criterion, whatever we say. I mean to die or not to die is a very important criteria. And also because so the, the methodologies said in order to calculate the number of persons, individuals per group, we need really criteria that are the most, I mean, easily identified with not, I mean, some doubts in this discussion. So this was. And also the other thing is that most of the studies and Patash studies and other studies have found this over mortality in this group. So the mortality was also the main criteria.

But at the same time we specified several secondary endpoints which are more, let’s say geriatric endpoints about function, about other, let’s say cognitive status, false fraction and so on. Globally we didn’t find differences between the two groups. The only difference we have found, I’m talking about pre specified endpoints. Okay. I mean, you know, what is the statistical analysis plan which very important to say that it’s not criteria. You add a postdoc analysis. We are talking about ad hoc analysis. And in those the only difference was the mortality from COVID because partially this study, I mean happened during the COVID pandemic, which was very important in France, as you know, and not only France, of course, but in France also before the vaccination.

And so this difference in mortality for Covid was the following. We had three times more deaths in the control group as compared to the deprescribing group. We don’t know exactly. We are trying to understand if this is related to the type of the medications who had been started or not. We are now there are analysis ongoing. This is the observation we have. And the difference. We didn’t have any other difference. The two groups have the same, let’s say, side effects, the same number of cardiovascular deaths or cardiovascular complications.

Eric 27:36

So no difference?

Athanase 27:38

No, no difference.

Eric 27:39

No difference Amongst most of the things you measured. Mike, did this surprise you?

Mike 27:45

No, it didn’t, No. I was hoping it would be positive but like I wasn’t surprised. And part of the reason is that like old people have a lot of stuff going on typically and it can be really hard to change these big picture outcomes. Like if we had a drug that I could prescribe tomorrow that decreased your overall risk of death by 25%. I mean, I’d have a nicer background right now. So. Not that it’s not nice already, but thank you. But you know, it’s. I think we like in the deprescribing world, we sometimes kind of handicap ourselves because the outcomes we tend to look at are these things which are really hard to change in older adults, like mortality, hospitalization, quality of life. These are really important.

But these are really hard to change from any intervention, pharmacologic, non pharmacologic, whatever. And because we sort of are forced to look at these more global interventions, we come up this, we have these studies which show we deprescribe, we don’t affect the outcome. We consider it a negative study. You know, but if you contrast that to prescribing studies, like I’ll use the case of Ezetimibe, this was like a multi billion dollar drug or at least, at least a billion dollars of sales. You know, how was it approved by the US fda because it reduced the thickness of the intima of your carotid artery.

This kind of very upstream clinical outcome, everybody said, oh, that’s a win. We think that’s gonna translate to better downstream outcomes. They can make billions off this drug. And in deprescribing we say, okay, our, our threshold is we have to prove you, you know, it makes you die less often. I mean, I put you on that,

Eric 29:25

Mike, because I was in agreement until I saw Sprint. That was like a 30% reduction in mortality in older adults.

Mike 29:33

Yeah.

Eric 29:34

And non nursing home patients. But that’s something not to sneed it at.

Mike 29:38

No, no it isn’t. Sometimes, I mean, sometimes we have these major successes, but you know, a lot of times we don’t. And it doesn’t mean that deep prescribing isn’t valuable. I think we’ll probably be talking about non inferiority. I mean the fact is like we can get these people on fewer meds and they have the same outcomes. Yeah. So they’re exposed to a fewer risk of adverse effects, less cost, less medication burden, less opportunity for drug, drug side effects, and you get the exact same outcomes. So like that’s a win. Even if people didn’t happen to die a lot less often after deprescribing.

Eric 30:12

Is that something we can say in our study that they’re equivalent? It’s not inferior, like.

Athanase 30:18

No, the study, the ARF hypothesis, initial hypothesis. Because in the observational studies who have this over Mortality was that if we reduce treatment and if we increase moderately systolic blood pressure. And this happened, I mean, in this study we have differences. We have lower number of medication in the interventional group and hypertensive medication. And we have actually a systolic blood pressure. It’s slightly significantly but slightly higher in the interventional group. So we obtained that and we believed initially that if this happen, we can have a lower mortality. So this is why we did a superiority study.

Now we have no difference. So when you see the results, of course our hypothesis initially was not confirmed. So now the question is, do these result with the absence of difference? Can we conclude really that there is no harm and this is not, I mean, detrimental to have to decrease the treatment? The answer is that since we have, you know, this is a very high mortality population, we had about. It’s three years follow up, more than three years follow up. It’s very, very long for this population. 60% of deaths in those two groups. Okay, 60%. And the analysis showed that what we call the hazard ratio, which is, it’s a mix of how many deaths and at what time death occur early or late. So the hazard ratio is 1.02, which means 2% difference, let’s say, okay, 2%.

And with narrow, they say, without entering the, let’s say, methodological and mathematical details, but the very narrow 95% confidence of limit of confidence. And all the methodologies, and the New England methodologies as well. And Art of Gold said, since we have this small, let’s say very small difference and very, very low error, let’s say limits, we can conclude that clinically there is no clinical difference in terms of the mortality between the two groups. And this, you know, the most strict journal, which is New England on that, accepted that. Okay, so what that means that the result is that I can have the same result in what we measured, except the COVID as I said, which is beneficial more for the prescribing.

But let’s forget that for the moment. I can have the same result with more, with less medication. Two strategies, which is the strategy I choose when I am in front of this situation, Do I have to choose the strategy with more medication, which is not more, only more expenses for health, but it’s anyway more, you said drug burden, which is more possible risk. Because we know that globally these patients, the most frail patients have more, I mean, much higher side effects, would use the medication. And I can tell you the other result that was the trend. But in my opinion, it’s a very important result. And this again was pre specified. We have decided from the beginning and it was in a statistical analysis plan to make the analysis of the benefits of each strategy according to the level of freight. As I said, globally this is a very frail population.

But in this population there was 10% of people that were fit according to the most usual and used scale, which is the clinical frailty scale. Okay, there were 10% of the population that were robust fit. There were about 20%, let’s say about vulnerable or mild frailty, about 25% people with moderate frailty and about 40% of severe frailty. And so it is in the paper, we have a clear trend which is not significantly the beats at the level of 00A, which means a little bit higher than the significance level. But you have a clear progressive, let’s say trend very progressive from one group to the other. The most fit patients get more benefits in terms of mortality. If you don’t stop the 10%, if you don’t stop the treatment and progressively you’re going to go from one, the first, the most fit to the most friend.

You have the opposite. In the most frayed patients we have non significant but very nice trend for having more benefits in mortality in those who deprescribe the treatment. And this the 008, it’s not because new England they don’t put any P after the main, but the trend you can see in the figures, it’s very clear. So what does it mean? Mean that what was our initial hypothesis, even if maybe the level of rate is a little bit more severe to say that. Which means that the thing is not age by itself, if I deprescribe or not, is the level of functionality, frailty and vulnerability to the problems, the medication related problems. And this again I repeat, it was not significant. But the trend is clear, is confirmed.

Eric 36:51

Okay, I got, I’m gonna ask Mike, what, what was your. Do you agree with all of that, Mike, when you’re, when you’re looking at these outcomes?

Mike 37:00

A hundred percent. And that was actually one of the key sort of take homes that I had from the studies that the overall result was negative. But there’s, you know, it didn’t reach the level of statistical significance. But there sure looked like there was a differential effect depending on how frail you are. And this makes the results more consistent with the Sprint study that you mentioned earlier because the fitter people seemed to. It wasn’t statistically significant, but they were trending towards benefiting from having their blood pressure lower.

And the frailer people were tending to benefit from having their blood pressure meds stopped. Now Sprint did some analysis where they also looked at frailty. But the distribution of frailty in Sprint I would anticipate would be very different than distribution of frailty here. Like what they called frail or sprint was probably closer to mildly frail in this study. So, so it’s apples to apples comparison.

Eric 37:53

Would you compare, would you say this is a negative study, Mike, but a positive deep prescribing study cuz you, you can either take less medications and get the same results or better depending on your frailty study, frailty status or yeah, frailty status.

Mike 38:11

I would almost hesitate to use the words like positive or negative here because like negative kind of implies that it failed. Like and there’s nothing here that failed. This provided us really useful information and the first is that globally for everyone, you know, keep the meds if people want, stop the meds if if that seems like it’s consistent with the patient’s values and goals and other stuff and you’ll probably end up rupp on it. Population average roughly in the same place. So that’s good to know. But then also this frailty thing, you know, so when I manage my patients differently based on their level of frailty.

Probably yeah. I mean it’s not definitive data but show me better data that is available. There isn’t any out there. And combined with all the other stuff that we do know and just general common sense, it does make sense that you know, thinking that people are frail are more likely to not tolerate having their blood pressures too low or being on polypharmacy. So all this kind of adds up to add to my pre study hypothesis that maybe letting people with frailty helping to reduce some of their med burden and allowing the blood pressure to ride a little higher, you know, probably benefits them. And if someone is more robust, I’ve also been convinced by Sprint that it probably makes sense to try to get their blood pressure down. It does seem to help. So I think those are my kind of key clinical takeaways.

Nothing is certain. There’s not like P value is less than 0.0001 here and the effect sizes aren’t huge. But in the absence of better evidence and we ain’t going to get better evidence for a very long time. This to me I think provides important insights to help drive our clinical care.

Eric 39:51

Athanase, I’m going to ask you if

Athanase 39:53

I can add something. Sorry. Both hybrid study and spring spring study, spring study have included patients older than 80 for IBAD for instance. But there were All. And if you see the exclusion criteria, it’s not any problem of dementia. No. Any problem of autonomy, no heart failure, no heart failure, needing diuretics, converting enzyme, Hebrews or ARBS in order to start hypotension. And the one, the final was you have to, not to include the patients that you estimate over 80, that you estimate that they will have a major medical problem during the five years follow up period.

I mean, if you are a geriatrician or if you are, I mean a physician or whatever you are, you can say that these are very selected. And I was member of the IBET study. I was a physician. Yes. And during three years of inclusion, I included one patient because there are so many exclusion criteria. So if after that you make you say these are frail, these are not frail. I mean, these were not frail, just. I mean they’re very robust and partially robust patients. And I think for these patients we have several end spring also. So we have data to say, yes, we have to treat them. But what about the others?

Eric 41:25

Let me ask you this, because we do have one other study, the Danton study, which was actually referenced in a previous podcast of ours. Which podcast was that, Alex?

Alex 41:34

That was with this podcast that came out today, the day we’re recording it, on Deprescribing near the End of Life with Simon Mujart, I think mentioned that study. And that was a. Patients who have had dementia residing in nursing homes.

Athanase 41:49

Right, the doctor study.

Eric 41:51

Yeah. And I think a blood pressure cut off at 160.

Mike 41:55

Right?

Alex 41:55

Yeah. And the, the deprescribing study was stopped early due to no changes in quality of life and worsening side effects. Serious side effects. So the Data Safety Monitoring Board ended that study early. So I was gonna say, I was about to say, hey, my conclusion is the most frail patients, you know, maybe we should be deprescribing. And we excluded, in, in this present study in the New England Journal excluded patients with a life expectancy of less than three months. Well, those. But then we have that other study and it makes me confused, right? Like these patients with dementia in nursing homes were probably on the very frail end of the spectrum here, Right. If we were to compare. And they had to stop it early.

Athanase 42:42

Yeah. Can I answer?

Alex 42:44

Yeah.

Athanase 42:45

What do we do? Yeah, I mean, I know, well, the study, I know the people who did the study, we had many discussions before the results, their results, our results. There are three main differences. First, in the Danton study, they included people feeling a pressure, as you said, up to 160. So what was not the case in US we start 130 and lower. First difference, second difference. If you see the protocol, they stop all treatments in six weeks into six weeks. In our protocol, the reduction of the treatment was every six months. It was at the beginning, actually. Then at three months if pressure was still lower than 130 and then six and every six months only. So which means it was much longer.

I think older people, we have to understand. Yes. And the last difference, and I will tell you what’s my opinion. And the last difference was that we have fixed a threshold of alert if after reducing treatment blood pressure was over 160 to follow up and immediate rate in production of the treatment. If it was more than 180. In Danton, the criterion of reproduction was 200. So they started much higher. They did the reduction very quickly and they hit a fixed and over and upper limit very high 200. And there are some other differences. For instance, if you read the paper, they say that during the COVID period they started follow up mostly and very few visits.

So I think there was these problems and what I say the prescribing for me it’s a prescribe. It’s like prescribing. You have to know very well your patient. You have to follow rules according to the status of the patient, comorbidities, level of frailty and whatever. And go as we say also for prescribing, start low, go slow. In geriatric patients, same thing for the prescription. I mean stopping, let’s say someone with three anti hypertensive stabbing 3n hypertensive in a very frail people. Yeah, it’s not good. So the prescribing is like prescribing. I know that pharmaceutical companies do not like this sentence, but for me it’s exactly the same.

Eric 45:27

I. I got my last same rules.

Athanase 45:29

And the people have to be followed after that. Not just I stop the mitigation. Okay, that’s it.

Eric 45:37

Yeah, I, I love this and I love thinking about like individualizing the patient above you. Thinking about like the benefits and the risk in particular individual taking the data, drilling it down. I wonder if we can drill it down to our audience. When we think about the benefits of continuing hypertension treatment in nursing home patients. Like which patients are most likely to see that benefit of continuing treatments versus which patient populations in nursing homes are most likely to see the benefit of tapering it off or at least not the harms which is a benefit if you’re just taking less medicines. Mike, how do you think about that? Do you have a sense of looking at all these studies.

Mike 46:15

Yeah, my, my simplistic kind of take home from all of this is that if someone’s blood pressure is really high, get it down because it’ll probably help them. And what’s really high? Hard to know exactly, but 150, 160. Yeah, I would certainly treat that. If someone is taking antihypertensives and their blood pressure is now 120 or 110 and they don’t have a reason to be on this amper tensive, they don’t have AFIB or heart failure or something else, that’s a reason. Would I lighten up on their blood pressure load? It would depend on the patient.

If they were frail, I would very strongly consider it. If they were not frail, then I would think it would be more of a shared decision making conversation as to what are the potential actual and potential adverse effects from those drugs as well as, you know, what their experiences with the medications and medication burden.

Eric 47:01

Athanase, would you agree with that or would you have stipulations?

Athanase 47:06

I fully agree and I repeat, the most important thing is to respect rules. But we showed for the first time in retreat frail that this is possible even in patients who were at very high cardiovascular risk and very frail. If you follow the rules, which are just clinical rules we respect for any prescription, deprescribing antihypertensive medication is possible and may be beneficial for the patients.

Eric 47:35

I love that. I think that’s a great transition to Alex playing a little bit more of Edith Paya.

Alex 47:46

I just had to say something in French. Here’s a little bit.

Alex 48:00

(singing)

Mike 48:27

Wonderful.

Eric 48:29

Thank you both for being on this podcast. That was wonderful and wonderful study upon us.

Mike 48:35

Merci.

Athanase 48:35

Thank you very much.

Eric 48:38

And to all of our listeners, thank you for your continued support.

This episode is not CME eligible.

For more info on the CME credit, go to https://geripal.org/cme/