Heart Failure Management in 2023: Challenges and Opportunities

2023

This publication summarises a presentation given by Associate Professor Gerry Devlin at the 2023 Goodfellow Symposium. With the aid of case studies, Dr Devlin discussed the evidence supporting the early and optimal use of foundational medicines in the management of heart failure with both reduced and preserved ejection fractions, providing practical recommendations for the management of heart failure in primary care. This review is sponsored by an educational grant from Boehringer Ingelheim and Eli Lilly.

Epidemiology

The burden HF places on health systems around the world is substantial. The NZ situation is similar where there were estimated to be 68,000 adults with HF in 2021/22.1 The prognosis for these patients is frequently poor with one in three who present to hospital with HFrEF dying within 3 years.2 Although the prognosis is better for patients who present with HFpEF, there is still significant morbidity and mortality in this group at 3 years. Hospitalisation with HF increases a patient’s mortality risk six-fold. The burden of HF is also higher in Māori and Pacific Island communities which is unacceptable.

Patients with HF interact with primary care on average 12 times per year, with three consultations specifically related to HF symptoms. These are opportunities for primary care to help patients and their whānau improve patient health and keep them living in the community.

CASE STUDY 1: Typically seen in primary care with class III-IV symptoms, i.e. breathless on minimum exertion and waking at night with breathlessness

Medical history Examination and investigations Medicines at discharge

• 64-year-old male

• NYHA Class III-IV symptoms

• Anterior MI 2 years prior with late presentation and did not receive reperfusion therapy

• Angiography was performed after 4 days and PCI due to total LAD occlusion

• EF was 40% at discharge

• BP 150/94 mmHg

• Tachycardiac with irregular rate of 100 bpm

• No murmurs and occasional bilateral crackles

• JVP was not elevated

• Chest X-ray revealed cardiomegaly and interstitial oedema

• ECG shows sinus tachycardia with Q-wave anterior to prior MI

• NT-pro BNP = 564 pmol/L (elevated)

• Renal function is normal

• HbA1c = 44 mmol/mol

• Aspirin 100 mg/day

• Cilazapril 1 mg/day

• Metoprolol CR 23.75 mg/day

• Atorvastatin 20 mg/day

This patient has advanced symptomatic HF. A cardiac insult has affected his LV function, resulting in HFrEF. Medication compliance has been erratic and he has not attended primary care for 18 months.

Where do we begin with this patient?

Dr Devlin emphasised that it is important to have clinical objectives with any HF patient (HFrEF or HFpEF):3,4

1. Make the patient feel better by reducing symptoms and improving QoL.

2. Improve the prognosis by reducing mortality and preventing hospitalisation via evidence-based care.

3. Prevent disease progression, where possible, through management of factors such as blood pressure and coronary artery disease.

It is not sufficient to simply up-titrate the patient’s diuretic dose and leave other treatments unchanged because intensification of diuretic therapy is associated with poor outcomes. Increasing the diuretic dose for a patient with HF may help to relieve symptoms, but in the long-term it is a poor prognostic marker that in terms of mortality is approximately equivalent to hospitalisation (Figure 1). Consideration of diuretic up-titration should therefore be a checkpoint, potentially triggering additional interventions to improve the patient’s prognosis.

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ESC 2021 guidelines

Dr Devlin highlighted, and later expanded upon, the ESC 2021 HF guidelines recommending (level 1A) four pharmaceutical interventions for patients with NYHA class II-IV with LVEF ≤40% to reduce the risk of HF hospitalisation and death:6

1. An ACE inhibitor.

2. A beta-blocker.

3. An MRA.

4. Dapagliflozin or empagliflozin.

The dosing of ACE inhibitors and beta-blockers is important. At a minimum, the aim should be to achieve at least 50% of the recommended dose. Reaching <50% of the recommended ACE inhibitor/ARB and beta-blocker dose was associated with an increased risk of death and/or HF hospitalisation.5 Patients reaching 50-99% of the recommended dose had a comparable risk of death or HF hospitalisation as those achieving ≥100% (Figure 2). ARBs are being increasingly initiated in preference to ACE inhibitors for HFrEF because the subsequent transition to an ARNI may be easier. ARBs are as effective, but not superior to an ACE inhibitor for HFrEF as two studies have shown no significant difference in outcomes for patients treated with either medicine.8,9

Mineralocorticoid receptor antagonists

The recommendation for MRA treatment in the ESC 2021 HF guidelines has undergone an important change since 2016. An MRA should now be considered early for asymptomatic patients with HFrEF.6 Previously, the recommendation was for MRA initiation for patients who remained symptomatic following treatment with an ACE inhibitor and a betablocker. Combining an ACE inhibitor, a beta-blocker and an MRA can reduce mortality over 1-3 years by 50-60%.10

Dr Devlin pointed out that MRA treatment is an opportunity to improve outcomes for HF patients in New Zealand because historically this class of medicine has been viewed with caution due to the risk of hyperkalaemia and worsening renal function. Treatment with an MRA needs to be considered more often and earlier in patients with HFrEF.

Dr Devlin emphasised the importance of explaining the expected benefits of treatments to patients when medicines are initiated. In the case of spironolactone, treatment is given to improve symptoms, prevent worsening HF and to increase survival. Symptom improvement should occur within a few weeks of beginning treatment. Due to the risk of renal complications during acute illness, patients should be advised to avoid over-the-counter NSAIDs and to temporarily stop spironolactone and contact a physician if diarrhoea and/or vomiting occurs. Painful gynaecomastia is the most frequent reason for patients being unable to tolerate spironolactone.

Eplerenone is funded indefinitely under Special Authority for patients with HF and EF <40% who are either intolerant to optimal dosing of spironolactone or who experience a clinically significant adverse event while taking an optimal dose of spironolactone. This means any prescriber who is treating a patient with HF can potentially prescribe funded eplerenone. The dosing of eplerenone is the same as for spironolactone.

Dapagliflozin or empagliflozin

A meta-analysis of the EMPEROR-Reduced and DAPA-HF trials (n = 8,474) found that in patients with HFrEF, SGLT2 inhibitors were associated with significant reductions in end-points, including:11

• 13% reduction in all-cause mortality (HR 0·87, 95% CI 0·77–0·98; p=0·018)

• 14% reduction in CV mortality (HR 0·86, 0·76–0·98; p=0·027)

• 26% relative reduction in the combined risk of CV death or first HF hospitalisation (HR 0·74, 0·68–0·82; p<0·0001)

• 25% decrease in the composite of recurrent HF hospitalisations or CV death (HR 0·75, 0·68–0·84; p<0·0001)

• Reduced risk of the composite renal endpoint (HR 0·62, 0·43–0·90; p=0·013)

The benefit of SGLT2 inhibitors in patients with HFrEF occurred regardless of the presence or absence of diabetes, the age of the patient, their gender, the presence or absence of ARNI treatment or their baseline health status. Furthermore, the benefit of an ARNI appears to be augmented by SGLT2 inhibitor treatment. The reduced progression or renal dysfunction in HF patients is an important additional benefit of SGLT2 inhibitor treatment.

Sacubitril/valsartan

The ESC 2021 guidelines state as evidence level 1B that:6

• Sacubitril/valsartan is recommended as a replacement for an ACE inhibitor in patients with HFrEF to reduce the risk of HF hospitalisation and death.

Sacubitril/valsartan is associated with:

• A 20% reduction in the risk of CV mortality, compared to an ACE inhibitor.12

• A 21% reduction in the risk of HF hospitalisation, compared to an ACE inhibitor.12,13

• Improved physical and social activities and improved QoL.14

• Comparable safety and superior efficacy vs ACE inhibitors when initiated after acute HF decompensation.13,15

SGLT2 inhibitors and ARNI can be safely initiated prior to discharge

Two important changes to the ESC 2021 guidelines are:6

• Optimal evidence-based oral medical treatment should be administered before discharge.

• An early follow-up visit occurs 12 weeks after discharge to assess signs of congestion, drug intolerance and to up-titrate evidence-based therapy.

These recommendations recognise the importance of establishing HFrEF patients on optimal care, before they are discharged from hospital, and of continuing to up-titrate therapy.

Dr Devlin highlighted data from the PIONEER-HF study showing that it is safe to initiate sacubitril/ valsartan in hospital following an admission for HFrEF.15

Safety and efficacy data from the EMPULSE trial show that in patients hospitalised with acute HFrEF and HFpEF, treatment with empagliflozin resulted in significant clinical benefit within 90 days, QoL improvements, and greater reductions in NT-pro BNP, compared to placebo with no safety concerns.16