Ahmed A has described in his publication here that the management of geriatric heart failure can be described using the following mnemonic: DEFEAT

  • D for Diagnosis: the process of management begins with a clinical diagnosis which must be established before pursuing an echo-cardiogram. Many geriatric heart failure patients may have normal left ventricular ejection fracture.
  • E for Etiology: the etiology must be determined.
  • F for Fluid: the fluid volume status must be carefully evaluated by examining the external jugular veins in the neck.
  • EA for Ejection frAction: an echo should be ordered to obtain left ventricular ejection fraction to assess prognosis and guide therapy.
  • T for Treatment: which consists of an angiotensin-converting enzyme inhibitor and a beta blocker. Diuretic and digoxin should be prescribed for all symptomatic patients with heart failure.

These all make sense but it seems that the management of heart failure has not changed much over the last decade or so.  But indeed there are some exciting interventions and drugs that are discussed in recent literature.

Two medications that are “new” for the management of heart failure are Entresto and Lancora.

Entresto

Entresto is a medication containing a combination of sacubitril and valsartan. Valsartan is an angiotension receptor blocker whereas sacubitril is a neprilysin inhibitor. Neprilysin is a neutral endopeptidase which is responsible for the metabolism of  various vasoactive peptides. Blocking neprilysin with sacubitril allows more vasoactive peptides to circulate around the body to help with sodium excretion. It is proposed that it may also have a remodelling effect in heart failure.

It is indicated for the treatment of heart failure with reduced ejection fraction (HFrEF) in patients with NYHA Class II or III, to reduce the incidence of cardiovascular death and heart failure hospitalization

Clinical Evidence:

In PARADIGM-HF which was published in New England Journal of Medicine in 2014, the use of Angiotensin-neprilysin inhibition was compared with enalapril where the primary outcome was all cause or cardiovascular mortality or hospitalization for heart failure. The results demonstrated angiotensin-neprilysin inhibitor to be superior to enalapril.

It is interesting to note that the Canadian Agency for Drugs and Technology in Health (CADTH) has completed an evaluation of this medication and made a recommendation to list the drug for the treatment of heart failure with reduced ejection fraction in patients  who meet the following criteria:

Clinical Criteria:
• Reduced left ventricular ejection fraction (LVEF) (< 40%).
• Patient has NYHA class II to III symptoms despite at least four weeks of treatment with a stable dose of an angiotensin-converting enzyme inhibitor (ACEI) or an angiotensin II receptor antagonist (ARB) in combination with a beta blocker and other recommended therapies, including an aldosterone antagonist (if tolerable).
• Plasma B-type natriuretic peptide (BNP) ≥ 150 pg/mL or N-terminal prohormone B-type natriuretic peptide (NT-proBNP) ≥ 600 pg/mL; or plasma BNP ≥ 100 pg/mL or NT-proBNP ≥ 400 pg/mL levels if the patient has been hospitalized for HF within the past 12 months.

Entresto is already approved and marketed in Canada. However currently it is not yet listed for coverage in Ontario Drug Benefits Formulary. One of the challenges is that monitoring of BNP or NT-proBNP may  not be readily available for primary care clinicians. Also the experience of Entresto is limited in individuals over the age of 80 and as such, I have not seen much experience of this medication in long term care setting.

Lancora (ivabradine) 

Ivabradine is another new medication that is recently approved in Canada. It is marketed under the name Lancora in Canada but more commonly known as the brand name Corlanor in the States. Ivabradine is the first hyperpolarization-activated cyclic neutrotide-gated (HCN) channel blocker.

HCN channel is responsible for the cardiac pacemaker and regulates the heart rate. Ivabradine thereby reduces the pacemaker activity of the sinoatrial node to reduce the heart rate with no effect on ventricular repolarization and on myocardial contractility.

According to the Canadian Product Monograph, LANCORA (ivabradine) is indicated for the treatment of stable chronic heart failure with reduced left ventricular ejection fraction (≤ 35%) in adult patients with NYHA Classes II or III who are in sinus rhythm with a resting heart rate ≥ 77 beats per minute, to reduce the incidence of cardiovascular mortality and hospitalizations for worsening heart failure.

Ivabradine has demonstrated clinical experience in the following studies:

THE SHIFT Study – This was a randomized, double-blind clinical trial comparing ivabradine versus placebo in 6558 adults with sable NYHA class II to IV heart failure, LVEF ≤ 35% and a resting heart rate ≥ 70 bpm. The primary end point was a composite of first hospitalization for worsening heart failure or for cardiovascular death. The study demonstrated that ivabradine reduced the risk for the combined end point of hospitalization for worsening heart failure and cardiovascular death.

The BEAUTIFUL Study – This was a randomized, double-blind, placebo controlled study of 10917 patients with coronary artery disease, impaired left ventricular systolic function (LVEF < 40%) and a resting heart rate of ≥ 40 bpm.  The primary end point was a composite of time to first cardiovascular death, hospitalization for acute myocardial or hospitalization for new onset or worsening heart failure.  Ivabradine treatment did not affect the primary composite outcome (hazard ratio 0.91, 95% CI 0.81-1.04, p=0.17), cardiovascular death, or admission to hospital for new-onset or worsening heart failure. However, it did reduce secondary endpoints: admission to hospital for fatal and non-fatal myocardial infarction (0.64, 95% CI 0.49-0.84, p=0.001) and coronary revascularisation (0.70, 95% CI 0.52-0.93, p=0.016).

The SIGNIFY Study – this was  a randomized, double-blind study of 19102 adults with stable coronary artery disease but without clinically evident heart failure (NYHA class I). Beta blocker therapy was not needed in this setting. The primary end point of this study was a composite of the first occurrence of cardiovascular death or myocardial infraction The authors concluded that among patients who had stable coronary artery disease without clinical heart failure, the addition of ivabradine to standard background therapy to reduce the heart rate did not improve outcomes.

Ivabradine may seem to have some promise as a new addition for the management of heart failure, specifically individuals with NYHA class II to IV heart failure. Given it can cause bradycardia, hypertension, atrial fibrillation, its use must be carefully monitored. It is also contraindicated in individuals with acute decompensated heart failure or systolic blood pressure below 90mmHg or diastolic pressure below 50mmHg.

Given it is only recently approved for use in Canada, there is still some lag time for its consideration in the Ontario Drug Benefits formulary. However, this may be happening soon.

In any case, both Entresto and Lancora are two new therapy options for the management of heart failure and we may see more prescriptions in the coming months.

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