Heart Failure Management in 2023: Challenges and Opportunities

Combination therapy

A meta-analysis of 75 trials (>95,000 participants) demonstrated that optimised, combination, evidence-based therapies are the most effective strategy in HF.17 Replacing an ACE inhibitor with ARNI (sacubitril/valsartan) in combination therapy was associated with a greater reduction in CV mortality and HF hospitalisation (Figure 3).

via aggressive up-titration. High-intensity therapy was associated with a 34% relative reduction in the primary endpoint of HF readmission or all-cause death at 180 days This was driven by a 44% reduction HF readmission, a 26% reduction in CV death and a 16% reduction in all-cause death, compared to usual care. There was a slight increase in adverse effects in patients receiving high-intensity care, although there was no difference in serious adverse effects such as hypokalaemia and worsening renal function between the two groups.

The challenge is how to achieve this rapid up-titration of therapies once patients have been discharged. Dr Devlin introduced a novel algorithm for achieving HFrEF treatment targets within 3 months that involved up-titration of each therapy every 2 weeks:20

• Week 1 – Initiate ARNI + SGLT2 inhibitor

• Week 2 – Exercise and rehabilitation

• Week 3 – Initiate beta-blocker

• Week 4 – Exercise and rehabilitation

• Week 5 – Initiate MRA

Figure 3: Relative risk reduction for cardiovascular mortality or HF hospitalisation of different pharmacological treatment combinations. Adapted from Tromp et al (2022).17

Early initiation of optimal combination therapy is associated with significant reductions in HF mortality and hospitalisation. The accumulating evidence supporting combination therapy has resulted in the consensus recommendation to promote optimal care and minimise hospitalisations.1

An ARNI/ACE inhibitor, beta-blocker, MRA and SGLT2 inhibitor is recommended in all patients with HFrEF (Figure 4).

Euvolaemic

This novel approach resulted in a significant increase in the percentage of HF patients achieving maximally tolerated doses of all four classes of foundational therapies at 3 months (p<0.01).20

The involvement of pharmacists in optimising HF treatments is also helpful. One study evaluated the effectiveness of pharmacist-led HF clinics in optimising treatment for HFrEF patients.21 In 76 patients with 34% virtual consultations, pharmacist-led clinics resulted in a high uptake of optimally dosed, guidance-directed therapies as well as improvements in NT-pro BNP and LVEF.

CASE STUDY 1: 64-year-old male with decompensated HFrEF

Returning to this case study the recommended interventions included:

• A diuretic for symptoms.

• Switching cilazapril to sacubitril/valsartan after a 36-hour washout.

• The addition of spironolactone.

Diu r etic for symptoms of congestion

If LVEF ≤35% after 3 months: ICD and/or CRT (if QRS ≥130ms)

If SR ≥70 bpm + LVEF ≤35%: add ivabradine#

* ARNI preferred. ACE inhibitor can be considered as an alternative if problematic hypotension and consider switching to ARNI later. † Carvedilol, bisoprolol or metoprolol succinate recommended. ‡ Empagliflozin recommended. # Not funded for use in heart failure in New Zealand.

Figure 4: Treatment algorithm based on the presence or absence of clinical congestion. Adapted from Sindone et al (2022).18

Managing acute decompensated HF

Once again, Dr Devlin emphasised the importance of initiating all four foundational therapies as soon as possible in HF patients. In practice, this means that if a patient presents with acute decompensated HF, a small dose of all four therapies, i.e. an ARNI/ACE inhibitor, beta-blocker, MRA and SGLT2 inhibitor, is better than up-titrating one or two classes to maximum doses before adding additional therapies. A tailored approach to treatment can be considered to achieve this. For example, if the patient has tachycardia or AF, a beta-blocker can be added early and/or if renal dysfunction is present a SGLT2 inhibitor should be considered.

The STRONG-HF study demonstrated that patients who had been admitted to hospital with acute HF benefited from the rapid up-titration of guideline-directed therapy and that this approach was safe.19 The study randomised 1,078 patients to high-intensity or usual care prior to discharge. The intention of the high-intensity group was to achieve maximum-tolerated doses of guideline-directed therapy as quickly as possible

• Up-titration of metoprolol.

• Ideally, the addition of empagliflozin.

CASE STUDY 2: 71-year-old female with HFpEF

Medical History Investigations Medications

• Mild effort intolerance for 2-3 years, more pronounced recently

• No chest discomfort or palpitations

• T2D

• Hypertension

• Hyperlipidaemia

• GI reflux disease

• Overweight (BMI 27)

• BP 160/96 mmHg

• Heart rate 86/regular

• JVP +3 cm

• Bilateral pitting ankle oedema

• No sacral oedema

• Soft ESM, S4, no S3

• Occasional basal crackles

• Hb 118 g/dL

• eGFR 44 mL/min/m2

• HbA1c 57 mmol/mol

• NT-pro BNP 358 pmol/L

• LDLC 2.3 mmol/L

• Echocardiogram

- Normal LV size and contractility

- EF 54%

- Moderate LVH

- Dilated left atrium

- Impaired relaxation

- Aortic sclerosis

• Quinapril 20 mg/day

• Atorvastatin 40 mg/day

• Pantaprozole 20 mg nocte

• Metoprolol CR 47.5 mg/day

• Metformin 500 mg BD

The clinical picture for this patient was consistent with hypertensive heart disease with aortic sclerosis and the patient was diagnosed with HFpEF. The NT-pro BNP level was important in arriving at this diagnosis.