Deprescribing antihypertensives in frail older adults

[Music] Welcome to the Australian Prescriber Podcast. An independent, no-nonsense podcast for busy health professionals.

I'm Dr Laura Beaton, your GP host for this episode. And, we are speaking with 2 authors of an excellent article on deprescribing antihypertensive drugs in frail older adults today. During my medical training, when to stop a medication was rarely the forefront of my mind, but it certainly is in many of my patients' minds. ‘Do I have to take this forever?’ is a question I'm often asked. And with it, comes the responsibility to explain why. And so, when it comes to something like treating high blood pressure, it's easy to explain that the risks are low and the absolute benefit of medication continues to increase with age. However, it's equally important to ensure that in older age we consider that that benefit-to-risk equation may change. Overtreating or aggressively lowering blood pressure might actually put an older frail person at other risks and it might be more appropriate to reduce or stop their blood pressure medication.

To discuss all the nuances of these decisions, I'm joined today on the Australian Prescriber Podcast by Dr Aili Langford, an NHMRC Emerging Leadership Fellow, Sydney Pharmacy School, and Professor Sarah Hilmer, the Head of Department of Clinical Pharmacology and a geriatrician at Royal North Shore Hospital in Sydney. Aili and Sarah, thank you for your article and welcome to the show.

SH: Thanks, Laura.

AL: Thank you, Laura.

So to start off with, let's look at the problem we're faced with. High blood pressure is really common. It's a major risk factor for cardiovascular disease that actually can be really effectively reduced with antihypertensive medication. Can you take us through why this benefit–risk equation for treating high blood pressure changes over the lifetime of a person?

SH: I think, as a person gets older, there is actually very good evidence that antihypertensives and lowering blood pressure still can confer benefit when it comes to preventing cardiovascular risk. However, as we get older, we also get more vulnerable to side effects. The other thing that changes particularly when we get frail and old and really in our last couple of years of life is that we have less time to benefit from prevention, and some people at the end of life may in fact find that preventing a cardiovascular event is not their main priority.

Aili, in this article, you introduced the concept of deprescribing and what it is, what it isn't. Could you define for us what deprescribing actually is, and what are the important principles that we need to consider?

AL: Deprescribing is the process of trialling a dose reduction or stopping a medication completely when the current risks of harm outweigh the benefits for that individual person. And it's usually done in a collaborative model between the patient and their healthcare professional. And as Sarah said, really weighing up what is important and what are the potential benefits of continuation for that individual, compared to the possible harms or the benefits of deprescribing the medication. And in the context of our particular review, withholding an antihypertensive due to an intercurrent illness, so for instance, if someone had low blood pressure because they were experiencing sepsis and the medication had been withheld for a short amount of time, that is not really what we would consider [as] deprescribing in this instance. It's more that long-term dose reduction or cessation.

So what's the current state of evidence for deprescribing antihypertensives in older adults?

AL: A Cochrane review was published a few years ago, which looked at randomised controlled trial evidence of the benefits and harms of deprescribing antihypertensives. There were 6 randomised controlled trials that were included in this review. And, it found that it is possible to deprescribe antihypertensives in frail older people. However, the evidence was limited in terms of the long-term data and the long-term outcomes of deprescribing trials, because the follow-up was found to be 4 to 56 weeks. So we didn't have long-term data. But in terms of some of the benefits and harms, it was found that quite a number of people were able to reduce their dose or stop their medication. But that group did have slightly higher systolic blood pressure, compared to the control group.

I guess, it remains to be seen how clinically important is that slightly increased systolic blood pressure for that person at that time. There is another trial that you mentioned which is the OPTIMISE trial, as well as an observational study. And as a prescriber or as a ‘deprescriber’, I wonder if you could talk me through these newer studies and how you think it might inform what I should do.

SH: Sure, Laura. One thing I'll just add to the Cochrane data that Aili summarised so beautifully, is that, in the Cochrane study up to a third of people in the deprescribing group, compared to about 15% of the continuation group, experienced raised blood pressure, or had other reasons to restart the therapy. But that means that two-thirds of people had no reason to restart. And while the follow-up was short, at a maximum of a year, a year is a long time in a person in their last year of life.

So since that review, the OPTIMISE trial was conducted in the UK. It was a randomised controlled deprescribing trial. And, it looked at 569 patients aged 80 years and over who had a blood pressure, when measured in the clinic, with a systolic [blood pressure] less than 150 mmHg and who were using 2 or more antihypertensive drugs. And, in the investigator's opinion, they could have benefited from medication reduction, because they had polypharmacy comorbidities, nonadherence, or frailty. Patients were randomised to either cease one of their antihypertensives using a deprescribing algorithm, which [was] weaned pretty slowly, or to standard care. And they found no difference between the groups in the proportion of patients who maintained their systolic blood pressure below 150 mmHg at 12 weeks of follow-up. And, really no difference in serious adverse events or health-related quality of life. Systolic blood pressure was about 3 mmHg higher in the deprescribing group than the continuation group. And, medication reduction was sustained in about two-thirds of patients, very similar to what we saw in the Cochrane review. So, the difference with that OPTIMISE study to the older studies in the Cochrane review is that patients were taking 2 or more antihypertensives in the first place and only stopped one.

And that probably maps what we see in clinical practice quite well, where a lot of older people are taking more than one antihypertensive. And what it really says is in that situation, if their blood pressure is less than 150 [mmHg], they're taking more than one [antihypertensive], they're frail, have polypharmacy, comorbidities, difficulty with adherence, you can safely stop one of their antihypertensives and just monitor their blood pressure.

The other data that we presented in the paper was an Australian observational study of 239 frail older people who had an unplanned hospital admission and were discharged to a nursing home. And in that study, of the 239 people, 44 patients, which is about 18%, had 52 antihypertensive drugs ceased in hospital. And those antihypertensives could have been prescribed for any reason. The patients who had their antihypertensive drugs deprescribed had an increased 90-day mortality, about double when you did the adjusted odds ratio, compared to those without deprescribing.

Now, it's really hard to know what this means. The people in whom you deprescribe antihypertensives during an unplanned admission in hospital are probably people who are hypotensive, which means they were pretty sick in the first place and had a bad prognosis. They're also potentially people who you see as being at the end of life, where the potential benefit of cardiovascular prevention is no longer there. It's hard to know what that odds ratio means. We certainly don't think it's causative. It just suggests that in people who we do routinely deprescribe antihypertensives in hospital as part of our routine care, that represents a group who are at high risk of death.

When do you think deprescribing does happen, and when should we be thinking about it?

AL: Perhaps it may be difficult for clinicians to determine exactly when to deprescribe antihypertensives, because in our current Australian and international guidelines there's not clear-cut cutoffs or data to inform when it may be appropriate. More recent 2023 European Society of Hypertension guidelines have made a recommendation that this can be considered in patients who are 80 years or older, if they have low systolic blood pressure, and they've defined that as less than 120 mmHg, or in the presence of severe orthostatic hypotension or high frailty.

SH: Thanks Aili. And I would say that, as a clinician, the strongest trigger to stop antihypertensives is when people are getting side effects. Either they're getting postural hypotension and having falls, or getting other side effects that might be specific to the drug class. Like, for example, they're getting incontinence from the diuretics, or they're getting gout from their thiazide diuretics, or they're getting low sodium and confusion related to that which is not transient but persistent.

The other side of the equation, when the person is no longer getting benefit, is also worth thinking about. And again, that's a good thing to think about when you're doing a comprehensive review. For us, it would be in a clinic. For a GP, it might be when you're doing your annual 75 plus review, or when a person comes back from a hospital admission, or a specialist with a new diagnosis that really does change their prognosis. And when you sit down and talk about the person's goals of care, and what their priorities are, it may well be that on balance the benefit side has come down.

Now that we've covered the when, let's go through the how. And in your article you present the very aptly named CEASE framework, which is summarised in a very helpful table. How does the CEASE framework guide how you deprescribe?

AL: The CEASE framework is a nice acronym where there is a corresponding step to each letter within the term CEASE. The first step of this framework, C, is Current drugs, and this step is really about ascertaining all drugs that the patient is currently taking and determining what the indication for each of these medications is. And in the specific context of antihypertensive drugs, I think it's important to consider why the antihypertensive has been prescribed. Is it for hypertension, or is there another indication such as heart failure or diabetic nephropathy? Is there evidence of target organ damage or a history of secondary or malignant hypertension? And it's really important to have thoughts about what the indication is, because this may either give more confidence in perhaps the appropriateness of deprescribing, or conversely, it might determine why a medication should be continued and not be eligible for deprescribing.

We move on to the E within the CEASE framework, Elevated risk. And this is considering if the patient is at elevated risk of, or experiencing harm from, any of their drugs. So this might be some of our antihypertensive adverse effects. Sarah mentioned some of the drug- or class-specific adverse effects that we may expect to see. For example, oedema with calcium channel blockers, or there may be symptoms related to the blood pressure lowering effects of the drugs. So, things like orthostatic hypotension.

The term prescribing cascades is one that I'm sure many of your listeners would be familiar with, where a drug is actually prescribed to manage the adverse effects of another drug. So, an example is antihypertensives that may be prescribed following the initiation of a nonsteroidal anti-inflammatory drug, which may lead to increased blood pressure and then the antihypertensive is obviously prescribed to mitigate that, but if for instance the nonsteroidal is stopped, then perhaps the antihypertensive may be able to be ceased as well.

SH: So, A stands for Assess. And the idea is to assess the current benefit-to-harm ratio for each drug. And that depends on the strength of the current indications or likely benefits for each drug for that person. Then, looking to see whether there are any existing side effects and how severe they are, and thinking about any risk of future harm associated continuing treatment.

Once you've done that for each of the antihypertensives, then you Sort and prioritise. And you prioritise drugs for deprescribing according to their benefit, how easy it is to stop them, and what the patient would prefer to stop. And, when a person is taking multiple antihypertensive drugs, then you prioritise the drugs that have the weakest indication or the highest risk of harm to stop first.

So, when I think about weakest indication, I think ‘Is this drug just being used for primary prevention of cardiovascular disease?’ Or is it something like an ACE inhibitor that’s also being used for their heart failure with reduced ejection fraction, or for prevention of their diabetic nephropathy, or ophthalmopathy. And, I'll choose the one with the least indication. And, when I think about the highest risk of harm, it's very much in that individual. So, is this person at risk of falls? Well, I'll stop the thing with the highest risk of postural hypotension.

Then when I get to E for Eliminate, the idea is to implement a discontinuation regimen and monitor the person closely for withdrawal syndromes or rebound symptoms that might require restarting treatment. And usually, particularly in primary care, you would stop one drug at a time, and you would try to slowly taper it if you could, and that is because it would allow you to see which drug was contributing to the side effects, and even if you couldn't stop the drug completely, you might be able to at least use it at a lower dose. However, sometimes, you have to stop drugs more quickly, because the person is having really bad side effects. And in some settings, it's easier to stop drugs more quickly. In hospital, people talk about the red pen as the geriatrician’s scalpel. We can stop 2 or 3 drugs at once, because we can monitor patients really closely, and if they run into trouble we can jump in and restart. When you're doing something in primary care, clearly, it's not as safe to do that, and you have to move more slowly.

The other thing to think about under Eliminate is some drugs can't be stopped cold turkey, because they have bad withdrawal syndromes. When it comes to antihypertensives, that's reasonably rare, except for beta blockers and clonidine. So, when you stop a beta blocker, you've got to taper it really slowly to avoid a rebound phenomenon of angina, anxiety, severe hypertension, tachycardia, and sometimes even myocardial infarction. And similarly, if you stop clonidine suddenly, then you can wind up with withdrawal syndrome that has not only rebound hypertension, but also anxiety, and headache, and tremor, and insomnia, and it's pretty awful. So you really have to taper those drugs to avoid the withdrawal effects.

The other thing to say, in this implementation, it's really important to document exactly what you're doing, why you're doing it, and monitor the person appropriately, and make sure that the person and any other prescribers or healthcare professionals involved in their care or their caregiver understands what you're doing and why.

Can I ask, in primary care, how much of a dose reduction should we plan and over what timeframe do you recommend we do regular checks for people?

SH: There is no evidence to say how fast you should taper in primary care. But it's generally pretty safe if you reduce the dose by 25 to 50% every 4 weeks. You might want to go faster if the person's having side effects, but that's usually a safe way to go, and you can bring the person back and review them every 4 weeks or so, and then reduce the dose further by 25 to 50%.

When we're using the CEASE framework and we're getting to Eliminate, what kind of target do you recommend we look at? Your article mentions the STOPPFrail tool, what should we be aiming for?

SH: Again, the short answer is that there is no gold standard that's highly supported by level A evidence. And the STOPPFrail tool is what we chose to report in this article because it's the consensus statement internationally on what would be reasonable in a frail older person, which is considered to be a person in the last couple of years of life. And they recommend 130 to 160 mmHg as a systolic blood pressure target. But, it really comes down to a decision with the patient, weighing up any side effects they might be getting from the antihypertensives versus any benefits that they're likely to get from continuing treatment at that stage of their life.

Sarah, you mentioned before the importance of including patient's carers in these discussions. And I'm interested, when you bring up deprescribing in clinic and with your patients, how do you find these conversations go? What are the sticking points? And how do you make sure that this is done in a patient-centric way?

SH: Every person is different, Laura. But coming back to what I said earlier, people are usually very open to stopping a drug if it's giving them side effects that they can see. If they, say, come into hospital with a fall and they've got postural hypotension, then their main priority is not to fall again and they're very open to stopping the antihypertensive. When it gets to the stage of talking about reduced benefit, then it's really important to explain that this is not taking away treatment, because no one wants to pay for their treatment anymore, because they're not worth treating, but this is actually treatment that has a risk of harm and is not going to help them anymore.

The other sticking point that we get as geriatricians, and I'm sure you get as GPs is, ‘But my cardiologist told me that I needed to stay on this forever.’ And it is really important to talk to the person's cardiologist who often has a very longstanding relationship with the patient, and discuss why you think deprescribing's a good idea, and come to an agreement, because that's important for the patient to understand that we're all on the same page, helping the patient achieve their goals.

This leads me to round out the discussion today. Speaking to the importance of providing that clinical handover for deprescribing. What do you actually do to make sure that this is communicated? Because I can see a situation where a very well-meaning person restarts something that you've gone to great pains to appropriately deprescribe.

SH: True. And it's probably also fair to say that sometimes you might deprescribe something that someone's gone to great pains to titrate to a certain level. And so, it is really important to have those conversations. My practice is all in hospital. So, it's important that we talk to the person’s GP to try to understand why the person's on the drug, how long they've been on it, whether they've tried to stop it before, who else is involved in the prescription. And, certainly, for those of us working in a hospital setting, there is no point in doing something without everyone else agreeing, because we will never see the patient again, and anything we've done will disappear. So, really important to get consensus.

And similarly, in primary care, important to get consensus from any specialists involved. We try to make sure the patient has information about deprescribing when they go home. And that's not only the patient's handheld list of all their drugs that they get when they go home, but also, some specific information about any drugs that have been deprescribed in hospital, what to look out for in terms of withdrawal when they go home, and what to do if they get withdrawal, why we stopped it, and also the withdrawing regimen. Those are available on the New South Wales Therapeutic Advisory Group website. We don't have any for antihypertensive drugs at the moment, but we do have them for other drugs that are commonly prescribed in hospital, like proton-pump inhibitors, benzodiazepines and antipsychotics. And they're freely available to be used in primary care as well. They're not specific to hospital.

AL: And I was just going to add in, putting a pharmacy hat on myself, I also think it's really important to communicate with the person's community pharmacist if it's a decision that's made in hospital, because many older adults are using dose administration aids, and I think if those decisions aren't communicated, if it's still being packed in their regular medications, it's possible that it may be restarted when they go home.

SH: Thanks, Aili. And we should probably jump in with the community nurses too. So again, if community nurses are involved in medication administration, they need to understand the changes.

AL: Definitely.

I see an argument for adding a C to the end of the CEASE framework. Maybe isn't quite a snappy, but add a communication at the end, to make sure that that's included to really ensure best care. Thanks very much to Sarah and Aili for talking through this topic with us today. While the example we used was for antihypertensives, I'm sure our listeners can see how they can apply the principles of deprescribing into other areas of their clinical practice as well. I'd really encourage our listeners to look up the full article, which is available for free on the Australian Prescriber website.

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The views of the hosts and guests on this podcast are their own and may not represent Australian Prescriber or Therapeutic Guidelines. Aili Langford is supported by an NHMRC Investigator Grant and is a member of the Australian Deprescribing Network Executive Committee. Sarah Hilmer is a member of the Australian Deprescribing Network Executive Committee and chairs the New South Wales Therapeutic Advisory Group and Sydney Health Partners Geriatric Medicine Clinical Academic Group.