1. Start with a diuretic
In the majority of patients with symptomatic heart failure, the first-line medicine used is a diuretic, which will work
to reduce fluid overload to improve the patient’s symptoms, however, there is no evidence that diuretics improve mortality.1
A loop diuretic such as furosemide is recommended as these are usually more effective than thiazide diuretics. A reasonable
starting dose of oral furosemide for a patient in a community setting is 20 – 40 mg, once daily. Subsequent doses are
then determined by the response to treatment – an improvement in symptoms and a weight loss of approximately 1.0 kg/day.
Bumetanide (fully subsidised) is an alternative for patients who do not respond to adequate doses of furosemide. The recommended
starting dose for oedema is 0.5 – 1 mg, once daily. In severe cases, the dose may be increased up to 5 mg per day.7
Doses of diuretic that are too low will not clear the fluid overload effectively, and may reduce the patient’s response
to an ACE inhibitor when started and also can increase the risk of decompensation when a beta-blocker is initiated. Doses
that are too high may lead to removal of too much fluid, which increases the risk of hypotension and renal impairment,
particularly when an ACE inhibitor is started.
2. Add an ACE inhibitor and beta-blocker
The next step after the use of a diuretic is the addition of an ACE inhibitor (or an angiotensin-II receptor blocker
– ARB) to reduce symptoms and a beta-blocker to improve ventricular function. There is good evidence that ACE inhibitors
and beta-blockers improve both morbidity and mortality for patients with HF-REF.1
Guidelines vary as to which of these medicines should be initiated first as they are regarded as complementary.1,
8 If a patient has acute fluid overload, a beta-blocker may not be tolerated until the fluid is reduced, although
an ACE inhibitor can be initiated. Ideally both should be started as soon as practical after a diagnosis of HF-REF is
made, with an aim of achieving an ejection fraction of > 40% as this is associated with improved prognosis. ACE inhibitors
assist with LV re-modelling and beta-blockers can markedly improve the ejection fraction.1
Any medicine from the ACE inhibitor class can be used, e.g. cilazapril. ACE inhibitors tend to give effective control
of blood pressure and are generally well tolerated. If postural hypotension or other adverse effects occur, this is usually
at low doses and increasing the dose does not tend to significantly change the incidence or severity of adverse effects.
Initiation of an ACE inhibitor may result in an increase in potassium and creatinine. If the potassium is < 5.5 mmol/L
and the increase in creatinine is no more than 50% above baseline, these changes are acceptable. If potassium or creatinine
rises excessively, reduce the dose of the diuretic if there are no signs of congestion and stop nephrotoxic medicines
such as NSAIDs. If potassium or creatinine remain raised, the dose of ACE inhibitor should be halved and the creatinine
and electrolytes checked in one to two weeks. Discussion with a cardiologist is recommended as the ACE inhibitor may need
to be stopped.1,9
N.B. Guidelines for use of ACE inhibitors in people with chronic kidney disease take a more conservative approach and
suggest altering the dose of ACE inhibitor if creatinine rises > 30%.10
If an ACE inhibitor is not tolerated, an ARB can be substituted. Losartan is the only fully subsidised ARB available.
Candesartan is available under Special Authority (criteria are persistent ACE-inhibitor induced cough, history of angioedema
or inadequate control on maximum tolerated dose of ACE inhibitor). Adverse effects from ARBs are usually mild and transient
but may include headache, dizziness and gastrointestinal effects.
Beta-blockers approved for use in New Zealand for heart failure include metoprolol, carvedilol, and bisoprolol (see
”Bisoprolol – newly funded beta-blocker”). There is no clear evidence that any one of these medicines is superior to another,
but specific patient factors may guide the choice.11 For example, bisoprolol and metoprolol CR are once daily dosing,
which may be more convenient for some patients. Bisoprolol may be preferable in patients with atrial fibrillation as it
reduces heart rate more than other beta-blockers, but it also increases susceptibility to bradycardia. Bisoprolol may
be preferable in people with COPD compared to carvedilol as it is more cardio-selective.
When initiating a beta-blocker the recommendation is to start at a low dose, increase slowly and aim for the highest
tolerated dose (“go slow, aim high”). If a beta-blocker is initiated before an ACE inhibitor, e.g. in a patient with arrhythmia
or angina but without acute fluid overload, the dose should be increased to mid-range and then an ACE inhibitor started.
Bisoprolol – newly funded beta-blocker
Bisoprolol, a beta-blocker that is a highly selective for beta-1 receptor sites, has been fully subsidised in New Zealand since 1 May, 2012.
Tablet strengths are 2.5 mg, 5 mg and 10 mg. An initial starting dose is 1.25 mg, once daily, gradually increasing weekly
by 1.25 mg, aiming for a maintenance dose of 10 mg once daily.
Factors associated with a worsening prognosis
Factors that are independently associated with a worsening prognosis in people with heart failure include:4, 13, 14
- Age > 70 years
- Ejection fraction ≤ 30%
- Higher NYHA functional class
- Renal impairment
- High levels of BNP
- Co-morbidities including IHD, arrhythmias, diabetes, COPD, stroke
- Recurrent hospitalisation
3. Add spironolactone if still symptomatic
The use of spironolactone (the only subsidised aldosterone receptor antagonist), is recommended for patients who remain
symptomatic, or who have an ejection fraction < 35%, despite maximal doses of an ACE inhibitor and a beta-blocker. If
the patient’s LV function has improved somewhat with the use of an ACE inhibitor and beta-blocker, spironolactone may
not be required, however, consultation with a cardiologist and referral for echocardiography is recommended. Spironolactone
has been shown to reduce both morbidity and mortality in patients with heart failure. Spironolactone should be used with
caution in patients with impaired renal function and may cause hyperkalaemia. Renal function and electrolytes should therefore
be monitored regularly. Other adverse effects may include gastrointestinal symptoms such as nausea and diarrhoea.7
For further information see:
“Drug monitoring – Monitoring diuretics in primary care”,
Best Tests (Mar, 2009).
4. Add ARB, digoxin and anticoagulants as appropriate
If the patient has failed to respond to treatment with maximal doses of all these medicines, an ARB may be considered.
However, spironolactone would not usually be continued if an ARB is added as this combination (ACE inhibitor, ARB and
spironolactone) can worsen renal function. Discussion with a cardiologist is recommended.
Digoxin can be used to slow the ventricular rate and therefore improve symptoms in patients who have symptomatic heart
failure and atrial fibrillation. There is some evidence that digoxin may improve symptoms and reduce the rate of hospitalisation,
however, it does not improve mortality.1
N.B. All patients with heart failure and atrial fibrillation should be assessed using stroke risk assessment tools,
e.g. CHA2DS2-VASc to determine their need for anticoagulation.
For further information see:
"The use of antithrombotic medicines in general practice”,
BPJ 39 (Oct, 2011)