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Optimising heart failure therapies

15th September 2022
Computer generated image of human heart

Recent clinical trial data have led to new guidelines on managing heart failure with reduced ejection fraction, which promise to add years of life for people with the condition, many of whom also have diabetes. The need to adopt the Four Pillars of these new guidelines without delay was under discussion at the recent ADA conference, as Dr Susan Aldridge reports.

Speaking at the American Diabetes Association (ADA) Scientific Sessions this summer, Dr Patricia Campbell, Heart Failure Lead at Southern Trust Northern Ireland, reviewed best practice in diagnosis and treatment of people with heart failure with reduced ejection fraction (HFrEF). ”It’s important in the patient’s heart failure journey that they’re diagnosed early and accurately,” she says. “In the UK, 80% of patients are diagnosed when they’re already in hospital with an acute decompensated heart failure episode. This really is suboptimal, because heart failure is persistent and progressive. The pressure and volume overloads during acute decompensation drive cardiac remodelling, reduce contractile function and cause progression of the disease. So, after each episode, the patient never quite gets back to their previous level of functioning.”

On the other hand, we do know that optimisation of medical therapy early in the journey can prevent multiple hospitalisations and slow disease progression. “So, if there’s one message to take home from today it’s ‘think about BNP’. You guys [in your diabetes clinics] are looking after patients that I haven’t met yet, but they do have risk factors for heart failure. So, if someone has vague symptoms and you’re not sure what they’re related to, think about measuring their BNP.”

The Four Pillars of heart failure therapy

Most people with heart failure will already be on ACE inhibitors and beta blockers. However, the so-called Four Pillars of medication recommended in the most recent heart failure guidelines from the American Heart Association and other organisations are: angiotensin-receptor blockers/neprilysin inhibitors (ARNI, e.g. sacubitril/valsartan), beta blockers, mineralocorticoid receptor antagonists (MRA) and SGLT-2 inhibitors. Most of these have level A evidence for their efficacy in heart failure. For instance, the most recent trials on SGLT-2 inhibitors – DAPA-HF and EMPEROR-Reduced – show a 25% reduction in death or hospitalisation for heart failure with a number needed to treat of 21 over an 18-month follow-up. “In cardiovascular terms, that is an extremely low number needed to treat and therefore high-quality value medicine.” Dr Campbell says. 

She warns against clinical inertia. “You might think ‘I’ve got a patient in my practice with heart failure and they’re doing fine, so I’m not inclined to change anything’. Intuitively, we know that if a patient is newly diagnosed, or admitted to hospital, they are not stable and that warrants a change in therapy. We tend to think any stable heart failure is not at risk, but that is false. They are at risk of a decompensation episode if they have intercurrent illness, a new arrhythmia or atrial fibrillation, and are then at risk of sudden cardiac death.  These medicines are shown to reduce death or hospitalisation for heart failure, so we have to overcome our clinical inertia, even in the stable heart failure patient.”

Why these Four Pillars? Because each of these medicines acts on a different pathophysiological pathway – their mechanisms are independent and additive and their benefits are incremental. “So, the goal has changed from the last guidelines and it is now to implement as many of them as possible as quickly as possible,” says Dr Campbell. 

If you’re still not sure, because your patient is fine and they haven’t been in hospital in a few years, there is still a reason to change. Dr Campbell pointed to recent trial data, comparing comprehensive with conventional treatment, which showed that for a 55-year-old patient who is not particularly symptomatic, comprehensive treatment gave an extra 8.3 years of event-free survival, while a 65-year-old enjoyed an extra 6.3 years. “We are doing our patients a disservice if we are not maximising their medicines,” she says.

Implementing the Four Pillars

There are three changes to the way heart failure medication should be managed, according to the new guidelines. First, speed matters. “We have been too slow in introducing lifesaving therapies in the past, because we were doing it systematically according to the appearance of trial data,” Dr Campbell noted. Second, prioritise initiation of the Four Pillars and up-titrate afterwards. And third, there is no fixed or preference for the sequence of introducing these medications. “So, we are moving away from the approach that was vertical, step-wise, with titration to full dose of each drug before adding the next. It was chronological – based on order of completion of trials and assuming the most effective and well-tolerated treatments were developed first. This delays initiation of life-saving treatments that are immediately beneficial.”

For there is data from the CHARM-HFrEF trials on ARBs and from EMPHASIS-HF on MRAs that show the benefits start early, within two to four weeks. “These benefits happen, even when patients are in the early stages of being up-titrated. Even if you’re on tiny doses of an ARB or MRA, you’re still getting benefit. The same is true with SGLT-2 inhibitors. So, give the four pillars of care as soon as possible, and then up-titrate.”

She also suggests ignoring conventional sequencing and instead do these three steps. First, give the beta blocker and SGLT-2, then the ARNI and finally the MRA. This should all be achievable within three to four weeks, with up-titration to follow. This is in contrast to conventional sequencing, which takes six months or more.

Having said this, implementation should be individualised and adapted to the patient in front of you, according to their symptoms, functional status, renal function and comorbidities. “Also, you really should be getting these medications initiated before discharge from hospital after acute heart failure,” Dr Campbell advises. “It’s a time when you’ve got so many vital signs in front of you – lab results, and so on  – whereas we know in the real world there are multiple problems, such as patients not getting seen quickly enough after discharge or not often enough thereafter.”  

Barriers to implementation

Doctors worry that SGLT-2 inhibitors reduce estimated glomerular filtration rates (eGFR), for patients with heart failure often also have chronic kidney disease. It is the slight dip in eGFR on initiation that is the source of this concern. However, in the longer term, SGLT-2 inhibitors actually reduce the underlying decline in eGFR that occurs with chronic kidney disease. We also know from DAPA-HF and EMPEROR-Reduced that they reduce the risk of end-stage kidney disease and renal or cardiac death.

The presence of hyperkalaemia is also not a reason for not initiating these therapies, because both MRAs and dapagliflozin have been shown to reduce it. And when it comes to blood pressure, Dr Campbell notes that “A lot of heart failure patients won’t have a good, robust blood pressure, but SGLT-2 inhibitors are self-titrating in that those with lowest blood pressure get the lowest blood pressure drop and those with the highest blood pressure get the highest drop and this equalises out over time. So, low blood pressure should not be a reason not to start MRAs, SGLT-2 inhibitors and beta blockers.” Finally, SGLT-2 inhibitors have also been shown to have benefit for patients who are frail, so again, don’t hold back from using them in this group either. 

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Any opinions expressed in this article are the responsibility of the EASD e-Learning Programme Director, Dr Eleanor D Kennedy.