Stable Heart Failure – a need for urgency

Stable Heart Failure – a need for urgency

Supplied by Novartis
Entresto lady

Mary appeared stable last time she came to see you. She had been on her beta-blocker, angiotensin converting-enzyme inhibitor (ACEi) and diuretic since being diagnosed with heart failure with reduced ejection fraction (HFrEF) and hadn’t been troubled by any apparent side effects. Her left ventricular ejection fraction (LVEF) had been 33% upon initial diagnosis 18 months ago. Over the weekend she was admitted to hospital with symptoms of an acute decompensation of her heart failure. (not an actual patient).

Increasing frequency of acute events with disease progression leads to high rates of hospitalisation and increased risk of mortality.1,2 Just one heart failure (HF) hospitalisation puts patients at up to six times greater risk of death vs patients who had not been hospitalised for heart failure.3

Heart Failure is a chronic condition interspersed with acute episodes Adapted from Gheorghiade et al. 2005

34% of patients with New York Heart Association (NYHA) Class I-II heart failure with reduced ejection fraction die within three years of diagnosis1

In the PARADIGM-HF trial4,5 involving 8399 randomised HFrEF patients, 7.4% of patients on ACEi therapy died suddenly and a further 4.4% died because of worsening heart failure symptoms.6

So, are our “stable HFrEF” patients really that stable?

Does the "stable" heart failure patient really exist?

Research has shown that the majority of HFrEF patients a GP will see are mildly symptomatic i.e. NYHA class II patients.7

The research also found that heart failure patients saw their GP on average 12 times a year, of which three visits are specifically for heart failure related issues.9

  • Health-Related Quality of Life (HRQL) of patients with heart failure is markedly reduced compared with that in patients with other chronic diseases, demonstrating substantial limitations in physical and social activities.10

Adapted from The Criteria Committee of the New York Heart Association. (1994). Nomenclature and Criteria for Diagnosis of Diseases of the Heart and Great Vessels (9th ed.). Boston: Little, Brown & Co. pp. 253–256.
When should there be urgency to treat heart failure?

There is now available a fully funded medicine that has been shown to help HFrEF patients stay out of hospital, live longer and feel better - ENTRESTO® (sacubitril/valsartan).5,6,10-12

ENTRESTO® is a first-in-class Angiotensin Receptor Neprilysin Inhibitor (ARNI).11 It is one of the few heart failure therapies that definitively and significantly improves morbidity and mortality as well as physical and social activity limitations.10

Switching HFrEF patients on an ACEi with a LVEF < 35% to ENTRESTO® will deliver:

  • 20% RRR in cardiovascular death compared to ACEi therapy (p<0.001)
    ARR=3.2% / NNT=32 5,†
  • 21% RRR in time to first HF hospitalisation compared to ACEi therapy (p<0.001)
    ARR=2.8% / NNT=365,†
  • An improvement in QOL equivalent to 9 years of aging compared to ACEi therapy10

† = The primary endpoint of the PARADIGM-HF study was a composite of death from cardiovascular causes or a first hospitalisation for heart failure.5 NNT – Number Needed to Treat, ARR – Absolute Risk Reduction

ENTRESTO® utilises a multi-pathway mode of action to treating heart failure (HFrEF):

  • Sacubitril enhances the beneficial effects of natriuretic peptides increasing vasodilation and diuresis and reducing hypertrophy. 11,13
  • ​Valsartan inhibits the renin-angiotensin aldosterone system decreasing vasoconstriction and reducing hypertrophy as well as sodium and water retention. 11,13
Valsartan inhibits the renin-angiotensin aldosterone system decreasing vasoconstriction and reducing hypertrophy as well as sodium and water retention.

ENTRESTO® is initiated with a simple one or two step titration in patients with HFrEF 11

*Reduced starting dose recommended for patients with:11 • SBP 100-110 mmHg • age >75 years • severe renal impairment (eGFR <30 mL/min/1.73 m2) • moderate hepatic impairment (Child-Pugh B)• ACEi or ARB (Angiotensin Receptor Blocker) naive or prior treatment with a low-dose ACEi or ARB.

ENTRESTO® replaces the ACEi or ARB.
For patients currently on an ACEi a 36-hour washout period is required. No washout period is required for patients on an ARB. Patients switched to ENTRESTO® must not be restarted on an ACEi or ARB.11

1.Ahmed A. Am J Cardiol 2007;99:549–53.
2.Gheorghiade et al. Am J Cardiol 2005;96:11G–17G.
3.Okumura N et al. Circulation 2016; 133: 2254–2262.
4.McMurray JJ et al. Eur J Heart Failure 2013; 15: 1062-1073.
5.McMurray JJ et al. N Eng J Med 2014; 371(11): 993-1004.
6.Desai AS et al. Eur Heart J 2016; 36: 1990-1997
7.Taylor JC et al. Australian Family Physician 2016; 45(11): 823-827.
8.The Criteria Committee of the New York Heart Association. (1994). Nomenclature and Criteria for Diagnosis of Diseases of the Heart and Great Vessels (9th ed.). Boston: Little, Brown & Co. pp. 253–256.
9.Britt H et al. General practice activity in Australia 2014–2015. BEACH, November 2015.
10.Chandra A et al. JAMA Cardiol. 2018 Jun; 3(6): 498–505.
11.ENTRESTO New Zealand Data Sheet.
12.Pharmaceutical Schedule – Pharmac
13.Vardeny O et al. JACC Heart Fail 2014; 2: 663–70.
Mandatory Information
PRESCRIPTION MEDICINE. Entresto® 24mg/26mg, 49mg/51mg, 97mg/103mg (sacubitril/valsartan) film coated tablets. Consult full Data Sheet before prescribing, available from Entresto is fully funded under Special Authority Criteria, please refer to
Indication: Treatment of chronic heart failure (NYHA Class II-IV) with reduced ejection fraction.
Contraindications: Hypersensitivity to sacubitril, valsartan, or excipients. ACE inhibitors (ACEi). Do not administer within 36 hours of switching from or to an ACEi. Angioedema related to previous ACEi or ARB therapy. Use with aliskiren in Type 2 diabetes (T2D). Severe hepatic impairment, biliary cirrhosis and cholestasis. Pregnancy.
Precautions: Caution switching from ACEi or while co-administering with aliskiren in T2D (see Contraindications). Should not be co-administered with an ARB. May cause symptomatic hypotension, especially in those ≥75 years old, renal disease and systolic BP <112 mmHg or patients with an activated RAAS. Initiation not recommended in systolic BP <100 mmHg. Monitor BP when initiating therapy or during dose titration. If hypotension occurs, dose adjustment of diuretics, antihypertensives, and consider treatment of other causes of hypotension. If hypotension persists, consider dose reduction or temporary interruption. Correct sodium and/or volume depletion before starting treatment. May be associated with decreased renal function; assess renal function before initiation and during treatment. Monitor serum creatinine, and down-titrate or interrupt if a clinically significant decrease in renal function develops. May increase urea and creatinine levels in patients with renal artery stenosis. Not recommended with end-stage renal disease. Should not be initiated and consider discontinuation if the serum potassium level is >5.4 mmol/L. Monitor serum potassium periodically and treat appropriately, especially in patients with risk factors, dosage reduction or interruption may be required. Caution with medications known to raise potassium levels. If clinically significant hyperkalaemia occurs, consider adjusting the dose of concomitant medications. If angioedema occurs, immediately discontinue, and provide appropriate therapy and monitoring until complete and sustained resolution; black patients or patients with a prior history of angioedema may be at higher risk. Caution in NYHA Class IV or in moderate hepatic impairment or with AST/ALT >2X ULN. Use in lactation not recommended. Use contraception during treatment and for 1 week after last dose.
Interactions: Aliskiren in T2D, ACEi/ARB. Caution with statins, sildenafil, lithium, potassium-sparing diuretics including mineralocorticoid antagonists, potassium supplements, or salt substitutes containing potassium, NSAIDs including selective COX-2 Inhibitors, frusemide, inhibitors of OATP1B1/B3, OAT3 or MPR2 and metformin.
Dosage: Target dose one tablet of 97 mg/103 mg twice daily. Starting dose one tablet of 49 mg/51 mg twice daily. Starting dose one tablet of 24 mg/26 mg taken twice daily recommended for ACEi/ARB naive patients, those with severe renal impairment, moderate hepatic impairment, and in those ≥ 75 years old. Double every 2-4 weeks to the target dose.
Adverse effects: Very common (≥ 10%): Hyperkalaemia, hypotension, renal impairment. Common (1 to 10%): Cough, dizziness, renal failure, diarrhoea, hypokalaemia, fatigue, headache, syncope, nausea, asthenia, orthostatic hypotension, vertigo. Uncommon (0.1 to 1%): Angioedema, dizziness postural. Unknown: Hypersensitivity (including rash, pruritus, and anaphylaxis).
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NZ-00695 February 2020 TAPS NA11710 BGA200204