Improving treatment of systolic heart failure
Published in MedicineWise News
Date published: About this date
Clinical content may change after this date. This information is not intended as a substitute for medical advice from a qualified health professional. Health professionals should rely on their own expertise and enquiries when providing medical advice or treatment.
- Use ACE inhibitors/angiotensin II-receptor antagonists and beta blockers in all grades of systolic heart failure
- Consider aldosterone antagonists in patients with systolic heart failure who have symptoms despite being treated with standard doses of ACE inhibitors and beta blockers (note that monitoring of potassium levels is important)
- Regularly review all medicines and avoid drugs which may exacerbate heart failure
Use ACE inhibitors and beta blockers in all grades of systolic heart failure
Routinely manage everyone with systolic heart failure (New York Heart Association [NYHA] class I to IV [Box 1]) with a combination of an ACE inhibitor (or an angiotensin II-receptor antagonist) and a heart failure specific beta blocker (carvedilol, bisoprolol, metoprolol or nebivolol).1,2 These drugs reduce mortality and morbidity in all classes of systolic heart failure.2-14 Diuretics (typically a loop diuretic) are a routine addition as they control congestion and fluid retention but they should not be used as monotherapy.2
Box 1: New York Heart Association (NYHA) grading for heart failure symptom severity
|Class I – Asymptomatic
||No limitations in normal physical activity.
|Class II – Mild||Slight limitation of physical activity. Ordinary physical activity results in fatigue, palpitation, dyspnoea or angina pectoris.
|Class III – Moderate||Marked limitation of physical activity. Less than ordinary activity results in symptoms.
|Class IV – Severe
||Unable to carry out any physical activity without discomfort. Symptoms present at rest.
An ACE inhibitor for everyone with systolic heart failure
Unless there are contraindications, start everyone diagnosed with systolic heart failure on an ACE inhibitor as soon as possible. Angiotensin II-receptor antagonists are an alternative for those who develop a troublesome cough while taking an ACE inhibitor.2,15 ACE inhibitors and angiotensin II-receptor antagonists are both contraindicated in bilateral renal artery stenosis and during pregnancy.
Before starting an ACE inhibitor (or an angiotensin II-receptor antagonist) check renal function and electrolytes and review regularly.15 There is an initial risk of hypotension: advise patients to sit or lie down if they become dizzy or light-headed.
Patients should not take potassium supplements unless they are specifically advised to do so by their treating doctor.15
Titrate to target, consider beta blockers
Titrate ACE inhibitors to recommended target doses
ACE inhibitors have proven survival benefits at target dose levels.2,6 Aim to reach these dose levels (Table 1) by gradually increasing the dose (e.g. every 2 to 4 weeks) even if heart failure symptoms have resolved.
If an individual experiences worsening renal function or hypotension during titration of the ACE inhibitor dose, adjust the diuretic dose.2,6 If achieving target levels of the ACE inhibitor remains difficult due to intolerable adverse effects, titrate to the highest tolerated dose as this may still have some benefit.1,6,16
Consider beta blockers in people with stable heart failure
If a patient remains symptomatic after appropriate titration of an ACE inhibitor (or an angiotensin II-receptor antagonist), add a heart failure specific beta blocker.
Beta blockers may initially worsen heart failure symptoms.2,15,18 Start people with stable heart failure on a low dose once they are clinically euvolaemic and increase the dose slowly (at most every 2 weeks) to target (Table 1). Monitor heart rate, blood pressure and clinical status after each titration.6 Do not increase the dose while heart failure symptoms are unstable, or in the presence of bradycardia or symptomatic hypotension.15,17,19 These side effects are often transitory so wait until they subside before increasing the dose again.2
Ask individuals to weigh themselves daily when starting and titrating a beta blocker. Adjust their diuretic dose according to symptoms. Inform them that they should contact a health professional immediately if they gain or lose more than 2 kg over 2 days.2
Table 1: Recommended target doses of ACE inhibitors and beta blockers15,17
||Target maintainence dose
||6.25 mg three times daily
||25–75 mg twice daily
||2.5 mg daily
||10–20 mg twice daily|
||5–10 mg daily||20–40 mg daily|
||2.5 mg daily||20–40 mg daily|
||2.5 mg daily||5–10 mg daily|
||2 mg daily||4–8 mg daily|
||5 mg daily||20–40 mg daily|
||2.5 mg daily
||5–10 mg daily
||1.25 mg daily
||10 mg daily
||3.125 mg twice daily||25 mg twice dailyA|
|metoprolol extended release
||23.75 mg daily||190 mg daily|
||1.25 mg daily||10 mg daily|
Aldosterone antagonists may help people who remain symptomatic
If people have severe symptoms (NYHA class III or IV) despite taking an ACE inhibitor (or an angiotensin II-receptor antagonist) and a beta blocker, Australian guidelines recommend adding spironolactone.2 Although Australian guidelines suggest consideration of eplerenone if people have mild symptoms despite taking an ACE inhibitor (or an angiotensin II-receptor antagonist) and a beta blocker, it is not TGA approved or PBS listedB for this indication.2
Weigh the potential benefits against the risk of hyperkalaemia (see below) if considering adding an aldosterone antagonist.
Start spironolactone at a dose of 25 mg once daily. Reduce the dose to 25 mg on alternate days if hyperkalaemia occurs. If heart failure symptoms worsen consider increasing the dose to 50 mg daily if there is no evidence of hyperkalaemia.15
Trials of aldosterone antagonists suggest benefit
Two large studies of aldosterone antagonists (spironolactone and eplerenone) in people with systolic heart failure found they significantly reduced mortality and rates of hospitalisation.20,21
Spironolactone improves cardiovascular outcomes in people with moderate to severe heart failure (NYHA class III or IV) who are already taking a loop diuretic, an ACE inhibitor and digoxin. Beta blockers were not widely used for heart failure when this trial was conducted.20
Eplerenone improves cardiovascular outcomes in people with mild symptomatic heart failure (NYHA class II) who are already using an ACE inhibitor (or an angiotensin II-receptor antagonist), beta blockers and, if indicated, a diuretic.C However, while this group had mild symptoms they were still at high risk of cardiovascular events: all had been hospitalised because of a cardiovascular event in the previous 6 months.21,22 It is not clear if people with mild symptoms who are not at such high risk of cardiovascular events would benefit from adding eplerenone. There are no trials of spironolactone in people with mild symptoms but there is no reason to suspect its cardiovascular benefits differ from those of eplerenone.23,24
Monitor potassium levels regularly to avoid hyperkalaemia
Using an aldosterone antagonist with an ACE inhibitor or an angiotensin II-receptor antagonist increases the risk of hyperkalaemia. Do not use an aldosterone antagonist in people with severe renal impairment or in those taking both an ACE inhibitor and an angiotensin II-receptor antagonist.1,15 Monitor potassium concentrations frequently: every week for the first month, then monthly for 2 months, then every 3 months and when indicated clinically.15B. Eplerenone is only TGA approved for use in people who have evidence of heart failure and left ventricular impairment within 3 to 14 days of an acute myocardial infarction. It is only PBS listed for heart failure with a left ventricular ejection fraction ≤ 40% occurring within 3 to 14 days following an acute myocardial infarction. C. Please note: eplerenone is not TGA approved or PBS listed for this indication.
Regularly review all medicines and avoid those which may exacerbate heart failure
A 2008 NPS audit found that 20% of patients with systolic heart failure were taking a medicine or medicines — most commonly a COX-2 selective NSAID — that can exacerbate heart failure. Where alternatives exist, commonly used medicines to avoid include:
- conventional and COX-2 selective NSAIDs
- thiazolidinediones (e.g. rosiglitazone and pioglitazone)
- corticosteroids (e.g. hydrocortisone, prednisone, fluticasone)
- anti-arrhythmic medicines (except for heart failure specific beta blockers and amiodarone)
- non-dihydropyridine calcium-channel blockers (e.g. verapamil, diltiazem)
- tricyclic antidepressants.2,15
Clear information about medicines may assist adherence
A small Australian study found that inadequate or complex medication instructions were major contributors to non-adherence in people with heart failure.25 Provide clear information about each medicine and its role in managing the patient’s condition to assist in improving adherence.2
Assoc Prof John Atherton, Director of Cardiology, Royal Brisbane and Women’s Hospital, Brisbane
- Hunt SA, Abraham WT, Chin MH, et al. 2009 focused update incorporated into the ACC/AHA 2005 Guidelines for the Diagnosis and Management of Heart Failure in Adults: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines: developed in collaboration with the International Society for Heart and Lung Transplantation. Circulation 2009;119:e391–479.
- National Heart Foundation, Cardiac Society of Australia and New Zealand. Guidelines for the prevention, detection and management of chronic heart failure in Australia, updated July 2011, 2011. (accessed 17 August 2011).
- Flather MD, Yusuf S, Kober L, et al. Long-term ACE-inhibitor therapy in patients with heart failure or left-ventricular dysfunction: a systematic overview of data from individual patients. ACE-Inhibitor Myocardial Infarction Collaborative Group. Lancet 2000;355:1575–81.
- The SOLVD Investigators. Effect of enalapril on mortality and the development of heart failure in asymptomatic patients with reduced left ventricular ejection fractions. The SOLVD Investigattors. N Engl J Med 1992;327:685–91.
- Pfeffer MA, Braunwald E, Moye LA, et al. Effect of captopril on mortality and morbidity in patients with left ventricular dysfunction after myocardial infarction. Results of the survival and ventricular enlargement trial. The SAVE Investigators. N Engl J Med 1992;327:669–77.
- National Clinical Guideline Centre. Chronic heart failure: the management of chronic heart failure in adults in primary and secondary care. London: National Clinical Guideline Centre, 2010. (accessed 16 June 2011).
- Jong P, Demers C, McKelvie RS, et al. Angiotensin receptor blockers in heart failure: meta-analysis of randomized controlled trials. J Am Coll Card 2002;39:463–70.
- Pitt B, Poole-Wilson PA, Segal R, et al. Effect of losartan compared with captopril on mortality in patients with symptomatic heart failure: randomised trial — the Losartan Heart Failure Survival Study ELITE II. Lancet 2000;355:1582–7.
- Dickstein K, Kjekshus J. Effects of losartan and captopril on mortality and morbidity in high-risk patients after acute myocardial infarction: the OPTIMAAL randomised trial. Optimal Trial in Myocardial Infarction with Angiotensin II Antagonist Losartan. Lancet 2002;360:752–60.
- Pfeffer MA, McMurray JJ, Velazquez EJ, et al. Valsartan, captopril, or both in myocardial infarction complicated by heart failure, left ventricular dysfunction, or both. N Engl J Med 2003;349:1893–906.
- CIBIS-II Investigators and Committees. The Cardiac Insufficiency Bisoprolol Study II (CIBIS-II): a randomised trial. Lancet 1999;353:9–13.
- MERIT-HF Study Group. Effect of metoprolol CR/XL in chronic heart failure: Metoprolol CR/XL Randomised Intervention Trial in Congestive Heart Failure (MERIT-HF). Lancet 1999;353:2001–7.
- Packer M, Coats AJ, Fowler MB, et al. Effect of carvedilol on survival in severe chronic heart failure. N Engl J Med 2001;344:1651–8.
- Flather MD, Shibata MC, Coats AJ, et al. Randomized trial to determine the effect of nebivolol on mortality and cardiovascular hospital admission in elderly patients with heart failure (SENIORS). Eur Heart J 2005;26:215–25.
- Australian medicines handbook 2011. Adelaide: Australian Medicines Handbook Pty Ltd, 2011.
- Dobre D, van Veldhuisen DJ, DeJongste MJ, et al. The contribution of observational studies to the knowledge of drug effectiveness in heart failure. Br J Clin Pharmacol 2007;64:406–14.
- Cardiovascular Writing Group. Therapeutic Guidelines: Cardiovascular, Version 5 [eTG complete CD-ROM]. Melbourne: Therapeutic Guidelines Ltd, 2008.
- Scottish Intercollegiate Guidelines Network. Management of chronic heart failure: a national clinical guideline. Edinburgh: SIGN, 2007. (accessed 4 July 2011).
- Clinical Knowledge Summaries. Heart failure - chronic - Management. London: National Institute for Health and Clinical Excellence, 2010. (accessed 22 June 2011).
- Pitt B, Zannad F, Remme WJ, et al. The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. N Engl J Med 1999;341:709–17.
- Zannad F, McMurray JJ, Krum H, et al. Eplerenone in patients with systolic heart failure and mild symptoms. N Engl J Med 2011;364:11–21.
- Zannad F, McMurray JJ, Drexler H, et al. Rationale and design of the Eplerenone in Mild Patients Hospitalization And SurvIval Study in Heart Failure (EMPHASIS-HF). Eur J Heart Fail 2010;12:617–22.
- Armstrong PW. Aldosterone antagonists — last man standing? N Engl J Med 2011;364:79–80.
- MeReC. Does eplerenone have a role in mild heart failure? NPC Rapid review. Liverpool: National Prescibing Centre, 2011. (accessed 23 June 2011).
- Toh CT, Jackson B, Gascard DJ, et al. Barriers to medication adherence in chronic heart failure patients during home visits. J Pharm Pract Res 2010;40:27–30.