Medications Medications

ACE inhibitors (ACEIs), ARBs, beta-blockers, MRAs and diuretics form the basis of first-line pharmacological management of left ventricular systolic heart failure (HFREF). Treatment doses should be increased to those shown to be of benefit in the major trials or to the highest tolerated doses.

See Recommended target doses of HF medications.

ACE inhibitors

  • All patients with HFREF (ejection fraction <40%) should be started on a low-dose ACE inhibitor, unless this is not tolerated or is contraindicated
  • ACEIs prolong survival in patients with New York Heart Association Class II-IV HF; improve patient symptoms and exercise tolerance; and reduce hospitalisations for worsening HF


  • ARBs are recommended as an alternative for patients who experience ACE inhibitor-mediated adverse effects such as a cough. ARBs are generally better tolerated than ACE inhibitors due to the absence of kinin-mediated side effects
  • ARBs may also be considered for patients who remain symptomatic despite receiving ACE inhibitors; however, careful monitoring is required when adding an ARB to existing ACE inhibitor therapy
  • ARBs provide mortality and morbidity benefits in patients with systolic HF


  • HF specific beta-blockers (carvedilol, bisoprolol, metoprolol extended-release, nebivolol) should be initiated in all patients with left ventricular HFREF, unless contraindicated or not tolerated. The choice of beta-blocker depends on the characteristics of the drug (such as receptor selectivity, lipid solubility, drug metabolism and effects on renal perfusion), evidence base (e.g., nebivolol was only studied in an elderly population), and prescriber familiarity
  • Beta-blockers should only be initiated after a patient’s condition has stabilised, to avoid precipitating HF decompensation
  • Carvedilol (beta1, beta2 and alpha1 antagonist), bisoprolol, metoprolol controlled release (CR) (both beta1-selective antagonist) and nebivolol (beta1-selective antagonist with nitric oxide-vasodilatation activity) prolong survival and improve symptoms in patients with HF already receiving background ACEI therapy


  • Spironolactone is recommended for patients who remain symptomatic despite appropriate doses of ACE inhibitors and diuretics
  • Spironolactone reduces mortality and symptoms in patients with advanced HF
  • Eplerenone should be considered for patients who still have mild symptoms despite receiving standard therapies (i.e., ACEI , beta-blockers), or in the immediate post-MI period
  • Eplerenone reduces mortality and hospitalisations in the immediate post-MI period in patients with left ventricular systolic dysfunction, as well as in systolic HFREF patients with mild symptoms

Diuretics are used to control symptoms of fluid retention and maintain euvolaemia
They should never be used as sole therapy for HFREF as they do not improve survival in HF
Diuretics may be used in a flexible manner. Daily weight monitoring is an essential component in the assessment of fluid status and is useful in guiding diuretic dosing. Tools such as the patient daily diary may assist patients to monitor changes in their weight

Loop diuretics, such as frusemide, are potent diuretics and are often used in patients with HF. Bumetanide is another loop diuretic that may be beneficial in patients with reduced gut absorption due to HF as it has better oral bioavailability than frusemide. Thiazide diuretics (hydrochlorothiazide and metolazone) and potassium-sparing diuretics (amiloride) are used in clinical practice for patients presenting with 'resistant fluid overload'. There is limited clinical evidence to support use of a thiazide but it may be effective in patients with a degree of renal impairment

Ivabradine and digoxin are useful in selected patients. Other treatments include Hydralazine-isosorbide dinitrate, fish oil and iron infusions.


Ivabradine may be considered for patients with HFREF, with a recent hospital admission and who are in sinus rhythm with a heart rate >70 bpm despite receiving optimal beta-blocker therapy. Ivabradine decreases heart rate by inhibiting the sinus node

Ivabradine reduces cardiovascular mortality and HF hospitalisations in patients with symptomatic HFREF, who had a recent hospital admission and were in sinus rhythm with a heart rate >70 bpm


Digoxin may be considered in patients with ongoing symptoms of HF in combination with standard drug therapy (i.e., ACE inhibitor, beta-blocker and diuretic therapy). Digoxin is often prescribed to control ventricular rate in patients with co-existing AF

Hydralazine-isosorbide dinitrate

Hydralazine-isosorbide dinitrate combination should be considered in patients who are actually intolerant of ACE inhibitors and ARBs or for whom these agents are contraindicated

Fish oil

Fish oil in combination with standard drug therapy (i.e., ACE inhibitor, beta-blocker and diuretic therapy) has been found to be useful in patients with ongoing symptoms of HF

Iron infusions

Iron supplementation for iron deficiency

Management of acute decompensated HF aims to treat signs and symptoms associated with fluid overload, abnormal gaseous exchange and reduced tissue perfusion. Treatment must be individualised to the patient, depending on their haemodynamic and volume status.

Initial pharmacological treatment may include:

  • Frusemide: A potent diuretic in patients with evidence of fluid overload. It may be given IV to facilitate rapid drug delivery. Available evidence indicates that IV infusion of loop diuretics has a similar efficacy to IV bolus dosing
  • Nitrate therapy: For rapid relief of symptoms of congestion in normotensive or hypertensive patients, acting via smooth muscle vasodilation
  • Morphine therapy: For its haemodynamic and sedative properties, particularly in patients with restlessness, dyspnoea, anxiety or chest pain. Morphine should be used judiciously in acute decompensated HF as it has been associated with higher rates of mechanical ventilation and intensive care unit admissions, longer hospitalisations and increased mortality.[#peacock-wf-hollander-je-diercks-db-et-al.-2008]

Inotropes may be trialled in selected patients with signs of hypoperfusion, where symptoms include cold, clammy skin, renal or liver dysfunction, or for shock, in order to increase cardiac muscle contractility. Potential adverse effects of inotropes include arrhythmias and myocardial ischaemia.

Some medications can contribute to an acute exacerbation of HF. Patients should be regularly reviewed in order to avoid potential precipitants. These include non-steroidal anti-inflammatory drugs (NSAIDs), cyclo-oxygenase 2 (COX-2) inhibitors, non-dihydropyridine calcium channel blockers, thiazolidinediones (e.g., rosiglitazone) and corticosteroids.

For more detailed information refer to Potentially harmful drugs to avoid in heart failure.

Whilst there is limited evidence to support pharmacotherapy for HFPEF, therapy can assist in managing symptoms and underlying comorbidities. Symptoms often occur as a result of fluid retention and are controlled with diuretic therapy. ACE inhibitors/ARBs may be used in the treatment of the underlying hypertension rather than as treatment for HF. Similarly, beta-blockers are prescribed for pre-existing ischaemic heart disease, hypertension or atrial fibrillation.

  • Peacock WF, Hollander JE, Diercks DB, et al. Morphine and outcomes in acute decompensated heart failure: an ADHERE analysis. Emerg Med J 2008;25;205-209.