Why does heart failure matter?

“Heart failure is interesting because most people incorrectly think it’s a disease and it’s not actually a disease at all – it’s a clinical syndrome …… a collection of signs and symptoms [including] breathlessness, fluid overload and fatigue”, says Mr Forsyth. The syndrome can be brought on by a number of different functional or structural problems in the heart – most commonly left ventricular systolic dysfunction (LVSD).

Shared decision-making is critical to the effective management of heart failure. For this to work well, patients need to understand their disease and its associated risks and also the risks and benefits of the available treatments. In addition, clinicians need to understand what the patient wants to get out of treatment.

How should the four pillars of therapy for heart failure be prescribed?

Current thinking advocates the use of ‘four pillars of heart failure therapy’.  The four pillars of therapy comprise:

• A renin-angiotensin system inhibitor (RASi) which could be either and angiotensin converting enzyme (ACE) blocker or an angiotensin receptor–neprilysin inhibitor (ARNi)
• A beta-blocker
• A mineralocorticoid agonist (MRA)
• A sodium-glucose co-transporter 2 inhibitor (SGLT2i)

The four drug groups all work differently to slow the progression of the disease. ”The order in which you go probably isn’t as important as to really trying to get people on to them as quickly as possible and we try and tailor the approach to the individual in front of you”,  says Mr Forsyth. The next step is to adjust each medicine to the optimum dose – a process that involves frequent follow up and monitoring for therapeutic and adverse effects and often calls for a team approach.

What are the key challenges in the treatment of heart failure?

The key challenges in heart failure treatment include reaching the target dose, awareness of drug-specific issues that influence effectiveness and tackling adherence problems, says Mr Forsyth. “For three of the four pillars we normally start below the target dose then we have to build them up”, he adds. For SGLT2 inhibitors there is only one dose and so patients start on the optimal dose, he notes.

Variations in the responses to drug therapy can occur because of the intrinsic properties of the drugs and/or because of differences in the ways that individuals absorb, metabolise and excrete drugs. In addition, other factors also need to be taken into consideration including the available evidence for effectiveness and the side effect profiles of the different drugs within the same class. A good understanding of these factors enables clinicians to individualise therapy appropriately.

Nevertheless, adherence can be a problem and it is a complicated, multi-factorial phenomenon. The best way to tackle adherence problems is to speak to the patient and find out what the barriers are so that an individualised solution can be found, Mr Forsyth advises.

Who should oversee heart failure management?

The management of heart failure treatment is probably best done by a primary care team and pharmacists can play a major role in prescribing, says Mr Forsyth.

Polypharmacy can be a complicating factor because some drugs may have contributed to the development of heart failure in the first place. A systematic review on polypharmacy in heart failure by Dr Janine Beezer and colleagues has explored the topic in detail.

Mr Forsyth’s advice to young pharmacists who might be thinking about specialising in cardiology is unequivocal: “There’s no better place to work as a pharmacist than in cardiology and heart failure.   Moreover, specialisation in cardiology also offers pharmacists considerable scope for prescribing, he adds.

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Polypharmacy can be a problem for patients with heart failure who may also be taking medicines for other conditions. A systematic review on polypharmacy in heart failure by Dr Janine Beezer and colleagues has explored this topic in detail, says Mr Forsyth. In many cases patients have other conditions – for which they receive drug treatment – long before they develop heart failure. In some cases, other medicines may have contributed to the development of heart failure. “We know that certain medicines can be implicated in causing heart failure in the first place – things like certain diabetic medicines or certain painkillers and so we must stop medicines because they’re actually worsening the scenario”, he says. “We shouldn’t just be looking at our drugs, we should be looking at all the other drugs that you’re [taking] and think about whether we can rationalize them a little bit, as well”, he adds.

Overseeing heart failure treatment

Management of heart failure patients is best undertaken by a team in primary care because “patients typically want to be treated as close to home as possible by the person that they have most relationship with and has the skills and the knowledge to treat them appropriately”, says Mr Forsyth. For much of the time prescribing and management decisions can sit in primary care, with occasional input from specialists, for example, when newly-diagnosed or when there is worsening of the condition. Once the specialist team has determined the causes of heart failure and designed a treatment plan, this can be delivered in primary care, although some improvements could be needed, he concedes.  When heart failure first develops patients almost always consult a generalist first – “a general clinician, a general practitioner, a general nurse, a general pharmacist or an acute general physician in the front of Accident and Emergency.  So, we cannot beat heart failure through specialists alone – we need our generalist colleagues, we need really upskilled generalist colleagues that know what heart failure is, the basics of how to diagnose it and really can [take] forward and follow treatment plans”, he says.

Cardiology pharmacy

Mr Forsyth’s advice to young pharmacists who might be thinking about specialising in cardiology is unequivocal: “There’s no better place to work as a pharmacist than in cardiology and heart failure”.

Working in a cardiology team satisfies the desire to help and care for people and to offer something meaningful to patients. “I would suggest to you that cardiology is one of the prime examples where a pharmacist can do those things. So, it’s very clear what we’re trying to do …… to prevent heart disease from re-occurring in the future. …… You get the ability to use your skill set as a pharmacist with these complicated factors – to look at the patient in front of you to try and get them on to the most appropriate and the best treatment. I believe that you can meet all of these conditions working in heart failure or cardiology as a pharmacist…….. You’ll go home thinking that you helped people and that’s probably what drew most people to pharmacy in the first place”, he explains.

Pharmacist prescribing

Specialisation in cardiology also offers pharmacists scope for prescribing. “From 2026 onwards all pharmacists that are leaving university will be independent prescribers from the first day that they register”, says Mr Forsyth. With appropriate governance and support, prescribing pharmacists can flourish in the cardiology team, he suggests. “I’ve got patients you can help; if you want to prescribe, come and work with me because I’ve got patients that [could] benefit from these four drugs that we want to give them and we can’t get them on to them quick enough”, he says.  “If you want to prescribe, we will help you and you help us and we all help the patient – and there’s very few places that are like that, so it’s a place that you can really find a home”, he concludes.

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Quadruple therapy with the ‘four pillars’ of treatment – a renin-angiotensin system inhibitor (RASi), a beta-blockers, a mineralocorticoid agonist (MRA), and a sodium-glucose co-transporter 2 inhibitor (SGLT2i) is now advocated for the treatment of heart failure. Reaching the target dose for each pillar is an important part of effective treatment. “For three of the four pillars we normally start below the target dose then we have to build them up. ….. We have a starting dose and then a target dose that we’re trying slowly to get to – so …… you might start on a quarter of the target dose and then maybe go up after a couple of weeks or a month to a half a target dose and then eventually to the full target dose”, explains Mr Forsyth. For SGLT2 inhibitors there is only one dose and so patients start on the optimal dose, he notes.  Individualising doses is important because “heart failure doesn’t just happen in old patients”, he says. Patients with heart failure can range from “very young, robust people to very elderly frail people – and not all of them can tolerate a full adult target dose”, he says.

Drug specific considerations

Variations in the responses to drug therapy can occur because of the intrinsic properties of the drugs and/or because of differences in the ways that individuals absorb, metabolise and excrete drugs.

Some drugs are water soluble some drugs are fat soluble; the way in which your body is made up ….. some people are obese, some people are very skeletal and thin – so where these drugs go in your body, how they’re distributed, how long they are retained within your body can be quite different from patient A to Patient B. How your body excretes them – metabolises them and passes them out of your body – are often affected by things like your liver and your kidney function. So, [these differences] might mean that and within a class of medicines you’re better looking at drug A rather than drug B”, says Mr Forsyth. Taking the example of beta blockers – “some are hydrophilic and some are lipophilic; some are very selective for certain receptors and reduce things like heart rate more than others, some are less selective. The side-effect profiles can be quite different because the lipophilic ones sometimes cross the blood-brain barrier and cause different types of side effects, so, again, you have to look at the patient in front of you. There might be a drug that is your kind of go-to drug if you’ve got no other great considerations but sometimes – and especially as you get more elderly – we have to try different combinations or different drugs within a class, he explains

Other factors that also need to be taken into consideration include the available evidence for effectiveness and the side effects profiles of the different drugs within the same class. For example, trials for spironolactone and eplerenone used different cohorts of patients – “quite symptomatic patients for spironolactone one in less symptomatic patients or post-myocardial infarction patients for eplerenone”, says Mr Forsyth. In addition, the side effects profiles differ; spironolactone is associated with gynaecomastia but eplerenone is not.  “It’s always the same, you treat the patient in front of you and you have to tailor the choice of the agent to the characteristics of that patient”, he emphasises.

Adherence

Adherence can be a problem but it is a complicated, multi-factorial phenomenon. The notion that the doctor or health professional tells the patient what to do and the patient follows the instructions to the letter is built on a number of assumptions “It assumes that you understand what’s wrong with you, you understand the instructions [and that] you understand the pros and cons [of the treatment]. It assumes that you want the treatment and you have some motivation to take it – you’ve chosen to take it.”, explains Mr Forsyth. It also assumes that there are no practical barriers to adherence. Mr Forsyth continues: “So the important thing with adherence is going back to basics [and asking], “Do people understand things and do they want the treatment?” …If the answer is ‘yes’ then we have to look for what’s stopping you. Is it something about your life? Is it something about cost? Is it something about another health conditions? Are you depressed? Are you cognitively impaired? Have you GI problems – are you vomiting things back up? Can you not read the labels? Do you speak in another language? Can you not understand the directions? “

The best way to tackle adherence problems is to speak to the patient and find out what the barriers are so that at individualised solution can be found, he concludes.

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“If you have the dominant variation of heart failure, which is the heart failure because of LVSD,  ….. this is where we know that there are four main classes of medicine that improve your survival chances and decrease things like your readmission to hospital and risk – and also improve the signs and the symptoms of the clinical manifestation of the syndrome of heart failure”, says Mr Forsyth.

The four pillars of therapy comprise:

• A renin-angiotensin system inhibitor (RASi) which could be either and angiotensin converting enzyme (ACE) blocker or an angiotensin receptor–neprilysin inhibitor (ARNi)
• A beta-blocker
• A mineralocorticoid agonist (MRA)
• A sodium-glucose co-transporter 2 inhibitor (SGLT2i)

The four drug groups all work differently and have additive effects and slow the progression of the disease. ”The order in which you go probably isn’t as important as to really trying to get people onto them as quickly as possible and we try and tailor the approach to the individual in front of you”,  he says.

For someone who also has high blood pressure this could mean starting with an ARNI because this will have the biggest effect in reducing blood pressure; for someone who is diabetic, the starting point could be an SGLT2i. For someone who has recently suffered a heart attack, an MRA – eplerenone – is a good option. If the heart rate is high or there is some angina pain, a beta blocker might be the best starting point.

“We have to look at the patient in front of you and look at what the risks of that individual patient are, and to understand them and their kind of unique constellation of signs and the symptoms – and that ….. lets us make some kind of judgment on what order to get you onto these four pillars”, Mr Forsyth emphasises.  In the past treatment used to be started in a specified order but experience has shown that this takes many months and “causes a lot of inertia” leading to patchy follow-up and failure to “get on to all four pillars”.  The process is quicker now but it remains a challenge to help patients to understand the complex treatment pathway and to start treatment promptly.

“We have a team-based approach with medics, with nurses, with pharmacists, …… that can quite intensively and quickly see them in these first few months of treatment to try and get them onto all four of these drugs. I think most of us don’t really care [about] the order you go in, as long as we treat you as an individual and trying to get them on over this this first few months”, he says.

“Over the last few years our international guidelines and some of our local guidelines really have flipped to trying to get these four drugs started, maybe at lower doses, as quickly as possible and then do the nudging with the doses rather than maximize one ….. and then the next one …….. and then the next one”, he adds.

Reaching the optimum doses

Optimum doses are derived from the seminal clinical trials, Mr Forsyth explains. However, treatment must be tailored to the individual and this involves frequent follow up and monitoring for therapeutic and adverse effects.

“So, it’s a mixture of quite cold therapeutic things about numbers but also talking to the patient and looking at their quality of life and symptoms while trying, where possible, to get them on to the dose closest to the target dose in the seminal clinical trials …… because that’s the dose that we know from the evidence that prevents the type of things like future heart failure events or improves …… survival. So, again, this is a complicated kind of moving dynamic and that’s why it’s quite labour intensive and that’s why, you know, it takes a long time to get people onto full treatment – or sometimes people stall and …. don’t quite get there. ….This is why a team-based approach with lots of different stakeholders is probably the better model for doing that”, he says.

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Mr Forsyth has worked predominantly with heart failure patients for the past 18 years. He has a small team of pharmacists that run outpatient clinics both in the hospital and in primary care for patients with heart failure or with left ventricular systolic dysfunction (LVSD). “LVSD is one of the structural diseases that can lead to heart failure after a heart attack”, he explains.  He and his team routinely deal with patients after hospital admission following them up to optimise their medical therapy, booking other tests when required and trying to get treatment plans optimised as quickly as possible. “Heart failure really has been my bread and butter – what I’ve lived and breathed for the best part of 20 years”, he says.

“Heart failure is interesting because most people incorrectly think it’s a disease and it’s not actually a disease at all – it’s a clinical syndrome …… a collection of signs and symptoms”, says Mr Forsyth.  These include breathlessness, fluid overload and fatigue and the syndrome can be brought on by a number of different functional or structural problems in the heart. LVSD is a common precipitating factor. “This is where the main pumping chamber of the heart, which is the left ventricle, isn’t pumping properly and that decreases cardiac output and that leads to the syndrome of heart failure. The most dominant version in the UK is left-sided, systolic heart failure, which is the LVSD variety, but that’s probably only in about 50-60 percent of patients; 40-50 percent of patients have another form of heart failure”, he explains.

Shared decision-making

The American Heart Association describes shared decision making in HF as ‘the process through which clinicians and patients share information with each other and work towards decisions about treatment chosen from medically reasonable options that are aligned with the patients’ values, goals, and preferences’.¹  “It’s an easy thing to write on paper  – it’s quite a hard thing to do in practice”, says Mr Forsyth.

It is important that patients understand their disease and its associated risks and also the risks and benefits of the available treatments. They also need to understand which aspects of the disease are affected by each of the treatments. In addition to educating the patient on these points, “it’s then more important to find out what matters to the patient themselves”, he emphasises. “So, I might say …. “I can offer you a treatment and that treatment might make you live longer” – and you’ll be surprised to know that perhaps that might not be the thing that’s mainly on people’s minds.  Maybe their symptoms are more important than the length of their lives; maybe, in some patients, the quality of their life might be more important than the length of their life; in some patients it might be the opposite [and] some patients …… might be happy just to take the risk of the disease untreated”, he explains.

These types of discussions can only take place in the context of a good, clinician-patient relationship. “This is quite a hard relationship ….. to build with a patient; it’s probably something that’s very hard to do in one appointment …….. Shared decision making is actually often done best by somebody that’s got a pre-existing relationship with the patient”, says Mr Forsyth.  This can be difficult for cardiac teams that may only have had brief contacts with a patient.  Sometimes primary care staff such as General Practitioners, practice nurses and community pharmacists are better placed for such discussions and a team approach my work best in the end, he acknowledges.

“At the end of the day, if the patient wants the treatment, they want it; if they don’t want it, they don’t want it. It is the patient’s choice to either accept or refuse a treatment, but we have to try and help them understand the pros and the cons before we help them make that decision, so this is hard. It’s an easy thing to write on paper – it’s quite a hard thing to do in practice”, he concludes.

References

1. Cited by Forsyth P, Beezer J, Bateman J. Holistic approach to drug therapy in a patient with heart failure Heart Published Online First: 10 March 2023. doi: 10.1136/heartjnl-2022-321764

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