Heart Failure- What do the Guidelines Tell Us?

Written by Dr Virginia Silvari, Senior Hospital Pharmacist (Cardiology), Cork University Hospital

Heart failure (HF) is a complex clinical syndrome where the efficiency of the heart is impaired and it is unable to meet the demands of the body. HF is a major healthcare concern as it is associated with high mortality, morbidity, and substantial economic burden on health care systems. 1

In patients with HF, the treatment goals are to reduce mortality, improve clinical status, improve quality of life (QoL) and prevent hospital admissions. 2 In 2021, the European Society of Cardiology (ESC) released the latest guidelines for the diagnosis and treatment of acute and chronic HF. 3 New concepts and recommendations make the 2021 guidelines a significant step forward from the previous ESC guidelines released in 2016. 4 From a Pharmacist’s perspective, the following points are of particular interest:

I. The introduction of new terminology for Heart Failure classification.

HF with midrange ventricular Ejection Fraction (EF) has been renamed in the 2021 HF guidelines as ‘HF with mildly reduced EF’ (HFmrEF) when EF is between 41-49%. This change in terminology was supported by the evidence gained in HF Randomised Control Trials (RCTs) that showed how patients with EF 41-49% benefited from similar treatment to patients with EF<40. 5

II. The 2021 Heart Failure guidelines recommend sacubritil/valsartan, an Angiotensin Receptor Neprilysin Inhibitor (ARNI), as a replacement for the Angiotensin-Converting Enzyme inhibitors (ACEi) or Angiotensin receptor blockers (ARBs) for patients with HF with reduced ejection fraction (HFrEF), where EF is <40%, to reduce the risk of hospitalisation and death. Two RCTs informed this recommendation:

• PIONEER-HF: Comparison of Sacubitril–Valsartan versus Enalapril on Effect on N-terminal pro b-type natriuretic peptide (NT-proBNP) in Patients Stabilized from an Acute Heart Failure Episode. 6
• TRANSITION: Comparison of Pre- and Post-discharge Initiation of Sacubitril/ Valsartan Therapy in HF With Reduced Ejection Fraction Patients After an Acute Decompensation Event. 7

The initiation of sacubitril/valsartan during hospital admission following acute HF decompensation not only caused a reduction in NT-proBNP, a biomarker of neurohormonal activation, hemodynamic stress, and subsequent cardiovascular events in HF patient, but also reduced the risk of hospitalisation. 6, 7 III. The Sodium-Glucose Co- Transporter 2 (SGLT2) inhibitors dapagliflozin and empagliflozin, are now recommended for patients with HFrEF to reduce the risk of hospitalisation and death. The RCTs that informed this recommendation were:

DAPA-HF: Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure 8

EMPEROR-Reduced: Empagliflozin Outcome Trial in Patients with Chronic Heart Failure and a Reduced Ejection Fraction. 9

The DAPA-HF trial which prospectively evaluated the efficacy and safety of dapagliflozin in patients with HFrEF, regardless of the presence or absence of diabetes, showed a 26% reduction of the primary outcome. The primary outcome was a composite of worsening HF or death from cardiovascular causes in patient treated with dapagliflozin in addition to standard treatment, compared to placebo and standard treatment. 8 The EMPEROR- Reduced trial which prospectively evaluated the efficacy and safety of empagliflozin in patients with HFrEF, regardless of the presence or absence of diabetes showed a 24% reduction of the primary outcome, which was a composite of death from cardiovascular causes or hospitalization for worsening HF in patients treated with empagliflozin in addition to standard treatment, compared to standard treatment and placebo. 9

The new evidence- based treatment options: the ARNI (in place of ACEi or ARBs) and SGLT2 inhibitors are now available for the optimal management of patients with HF. These agents have proven to help reduce hospitalization and mortality in patients with HF. In addition to β- blockers and mineralocorticoid receptor antagonists, ARNI and SGLT2 inhibitors have become a fundamental part of the Guideline-Directed Medical Therapy (GDMT) for HF.

Now that these new evidence based HF treatments have become a fundamental part of the GDMT, it is important/ imperative that healthcare professionals adopt the use of these medications in their practice to improve outcomes for HF patients

References available on request

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