PPR N P S Medication review for your patients with heart failure

N P S
PPR
National Prescribing Service Ltd
No. 8 May 2000
Prescribing Practice Review
Management of Heart Failure
Medication review for your patients with heart
failure
Patients with chronic conditions, such as heart failure, require regular medication review.
Medication history
Ask about pattern of medication use
Ask about prescription drugs, over-thecounter and complementary medicines
Non-compliance with drug therapy is an important
cause of treatment failure.
Consider drugs that may exacerbate heart failure;
Ask about perceived drug efficacy
▲ negative inotropic drugs such as verapamil and
diltiazem
How does the patient perceive their quality of life?
Are symptoms controlled?
▲ antiarrhythmics other than amiodarone
▲ beta-blockers, as well as being used to treat
heart failure, may exacerbate the condition
▲ NSAIDs and COX-2-selective NSAIDs2
▲ preparations high in sodium, such as urinary
alkalinisers
▲ complementary medicines containing willow
bark.
Problem identification
Are there any untreated indications?
▲ confirm the diagnosis of heart failure and other
co-existing diseases, eg atrial fibrillation
▲ consider if hypertension, hyperlipidaemia,
arrhythmias and diabetes are controlled
▲ consider an audit of your medical records to
check your patients taking digoxin for atrial
fibrillation are also on warfarin.
Have appropriate non-drug
measures been instituted?
Encourage patients to keep a symptom diary and a
set of scales to monitor their daily weight. Weight
gain may be an early sign of clinical deterioration1.
Smoking cessation, good nutrition, salt and alcohol
restriction should be addressed.
Moderate regular exercise should be encouraged in
patients with chronic stable heart failure1.
Ask about non-pharmacological
management
Consider physical activity, fluid restriction in
patients with congestion, sodium restriction and
weight reduction (if applicable). Ensure the patient
understands their condition and is able to monitor
and report changes in symptoms.
Vaccination against influenza and pneumococcus is
recommended to reduce the risk of serious
respiratory infection.
Is this medication regimen the most
appropriate for this patient?
Is drug therapy optimal to achieve your treatment goal
of improving prognosis and controlling symptoms and
signs of heart failure?
Is the patient taking an ACE inhibitor?
ACE inhibitors alleviate symptoms and reduce
mortality and risk of hospitalisation for heart
failure. They are now recommended as first-line
therapy for virtually all patients with clinical heart
failure, unless there are specific contraindications to
their use1,2,3 (see page 3).
Patients with contraindications to the use of ACE
inhibitors may benefit from other vasodilator
therapy (eg hydralazine and isosorbide dinitrate)1-3.
Consider specialist referral.
Is diuretic therapy optimal?
Diuretics should not be used alone in heart failure.
If required, add to ACE inhibitors to help control
congestive symptoms and signs1-3.
Most patients with moderate to severe heart failure
will require treatment with a loop diuretic
(frusemide, bumetanide or ethacrynic acid).
Thiazide diuretics are indicated for mild heart
failure and are less effective in renal impairment
and in the elderly. The addition of a thiazide to a
loop diuretic may be used in severe heart failure
with close monitoring3. Once good diuresis is
obtained patients may be educated to adjust
diuretic doses using daily weighing to monitor the
response (if necessary).
Would spironolactone be helpful in this patient?
Low-dose spironolactone (25mg), when added to
diuretic and ACE inhibitor therapy, can improve
prognosis in patients with severe heart failure 6. Its
benefits in patients with mild to moderate heart
failure are not yet known. Monitor serum
potassium frequently to avoid hyperkalaemia (see
NPS News, Issue 9).
Would the patient benefit from beta-blocker therapy?
Some beta-blockers have been shown to improve
prognosis in patients with mild to moderate heart
failure. They are increasingly being used in
combination with ACE inhibitors and diuretics in
the treatment of chronic stable heart failure 1,4.
Carvedilol is the only beta-blocker approved for
treatment of heart failure in Australia. There is
accumulating evidence that low dose metoprolol
has similar effects however, it is not approved for
this indication.
Beta-blockers can be difficult to use in heart failure.
To avoid complications, such as severe hypotension
and bradycardia, treatment should be commenced
at low doses and titrated carefully under specialist
supervision1,2,4.
Is digoxin indicated? Consider changes in evidence for
digoxin
Digoxin is indicated for use in heart failure in:
1. patients with atrial fibrillation
2. as a third-line treatment for patients in sinus
rhythm who remain symptomatic despite
optimal doses of ACE inhibitors and diuretics.
Digoxin can alleviate symptoms however, it does
not affect survival in this patient group8.
Carefully titrate the dose according to age, serum,
creatinine and serum digoxin levels to avoid
toxicity. Any hypokalaemia should be corrected
before commencing treatment.
Can angiotensin II receptor antagonists be used in
heart failure?
To date there is no consistent evidence that
angiotensin II receptor antagonists (eg candesartan,
irbesartan, losartan, telmisartan) improve longterm survival in heart failure. They are not
approved for the treatment of heart failure, but
have been suggested as an alternative to ACE
inhibitors in patients with a troublesome ACE
inhibitor induced cough1,2. Alternatively, there is
evidence that isosorbide dinitrate and hydralazine
are effective.
Table 1 - Doses of ACE inhibitors in heart failure
(from Therapeutic Guidelines: Cardiovascular 3rd ed 2)
Drug
Brand names
Starting Dose
Target Maintenance Dose
captopril*
Acenorm, Capace,
Capoten, Captohexal,
DBL, Enzace, SBPA
Amprace, Renitec
Monopril
Prinivil, Zestril
Coversyl
Accupril, Asig
Ramace, Tritace
Gopten, Odrik
6.25mg twice daily
50mg three times daily
2.5mg daily
5mg daily
2.5mg daily
2mg daily
2.5mg daily
1.25mg daily
0.5mg daily
10-20mg twice daily
20-40mg daily
20-40mg daily
4-8mg daily
20-40mg daily
5-10mg daily
2-4mg daily
enalapril
fosinopril
lisinopril
perindopril
quinapril
ramipril**
trandolapril**
* 2.5mg manufacturer’s recommended starting dose in sensitive patients, eg sodium depletion/high doses of
diuretics.
** approved for heart failure post-MI only.
2
Is there an ongoing need for these drugs?
Two questions need to be asked, are there mortality
benefits for patients and have any drugs been
initiated to treat adverse effects?
Is the dose, frequency and formulation
appropriate?
Consider doses of ACE inhibitors
▲ angioedema during previous ACE inhibitor
therapy
▲ pregnancy.
Contraindications/precautions to the use of betablockers
▲ decompensated, severe heart failure
▲ reversible airways disease and chronic
obstructive pulmonary disease
Whenever possible use at doses which have
demonstrated mortality benefits (see Table 1 for
target doses) 1,2,3,5. With careful dose titration and
follow-up high doses are achievable and well
tolerated in most patients1,5. Monitor blood
pressure, renal function and volume status.
▲ symptomatic bradycardia (< 50 beats/minute)
Consider doses of diuretics
▲ angioedema with ACE inhibitor.
Is the dose of loop diuretic achieving adequate
relief of symptoms of fluid retention? Monitor
carefully to achieve optimal dosing avoiding
volume depletion from overdosing or fluid
retention from underdosing. Increase the diuretic
dose if congestive symptoms worsen and decrease
when fluid retention is resolved.
Contraindications to the use of digoxin
If inadequate doses of diuretics are used when
congestion is present, this may diminish the
response to ACE inhibitors1.
Excessive diuretic doses can increase the risk of
hypotension and renal impairment with the ACE
inhibitor. Reduce the dose of loop diuretic if
necessary (eg low dose frusemide 20-40mg) to
enable the use of maximum tolerated dose of ACE
inhibitor7.
Would compliance be improved by changed dosing
times and frequency?
Discuss options for timing of diuretic doses with
the patient, eg taking the dose later in the day if
more convenient or splitting the dose.
Does the patient have contraindications to
any medications?
Contraindications to the use of ACE inhibitors
▲ bilateral renal artery stenosis, or a history of
anuric renal failure during previous exposure to
an ACE inhibitor
▲ advanced heart block.
Contraindications to the use of angiotensin II receptor
antagonists
▲ pregnancy
▲ intermittent complete heart block and second
degree atrioventricular block
▲ Wolff-Parkinson-White syndrome
▲ ventricular tachycardia
▲ cor pulmonale
▲ constrictive pericarditis.
Are adverse effects occurring?
The major adverse effects of ACE inhibitors are
hypotension, syncope, renal impairment,
hyperkalaemia, angioedema (rare), rash and taste
disturbance.
Dry cough is not an absolute contraindication to
the use of an ACE inhibitor but if troublesome,
therapy may need to be discontinued. Exclude
pulmonary congestion as the cause of the cough
before withdrawing the ACE inhibitor1,3-4. Consider
substitution of an angiotensin II receptor
antagonist on a private prescription.
Are there clinically important drug interactions?
(see Table 2 below)
Table 2 - Selected drug interactions
(see Australian Medicines Handbook for further information and a full list)
Drug
Interacting drugs
Interaction
Management
ACE inhibitors /
angiotensin II
receptor
antagonists
Loop or thiazide diuretics
Increased risk of 1st dose
hypotension
Lithium
Reduced excretion of
lithium and increased risk
of toxicity
Potassium & potassium
sparing diuretics
Increased risk of
hyperkalaemia
NSAIDs /
COX-2-selective NSAIDs
May reduce effect of ACE
inhibitor and precipitate
peripheral or pulmonary
oedema. Increased risk of
acute renal impairment
and hyperkalaemia
Enhanced hypoglycaemic
response
Withhold diuretic for 24
hours before initiation
of ACE inhibitor or
angiotensin II receptor
antagonist
Monitor serum lithium
levels when initiating,
ceasing or changing the
dose of an ACE inhibitor
Use with caution, closely
monitor serum
potassium
Avoid combined use. If
concomitant use
essential, monitor renal
function, serum
potassium and signs of
heart failure
Close monitoring of
blood glucose
Hypoglycaemic agents
Loop and thiazide
diuretics
ACE inhibitors/
angiotensin II receptor
antagonists
Increased risk of 1st dose
hypotension
Digoxin
Monitor serum
potassium levels and
supplement if necessary,
ensure correction prior
to initiating digoxin
Increased serum lithium
Monitor for signs of
levels
toxicity and serum
lithium levels, adjust
lithium dose if necessary
Use combination with
Reduced effectiveness of
caution, monitor renal
loop diuretics, increased
function
risk of nephrotoxicity
Use with caution and
Diuretic induced
hypokalaemia may increase monitor serum
potassium levels
the risk of arrhythmia
Lithium
NSAIDs /
COX-2-selective NSAIDs
Drugs that prolong the
QT interval
(eg amiodarone, sotalol,
terfenadine, astemizole,
cisapride,
anticholinergics)
Digoxin
Withhold diuretic for 24
hours before initiation
of ACE inhibitor or
angiotensin II receptor
antagonist
Diuretic induced
hypokalaemia may increase
the risk of digoxin induced
arrhythmia
Calcium, vitamin D and
calcitriol (with thiazides)
Increased risk of
hypercalcaemia
Monitor serum calcium
Diuretics
Corticosteroids
Diuretic or corticosteroid
induced hypokalaemia may
increase the risk of digoxin
induced arrhythmia
Increased serum digoxin
levels; additive negative
effects on heart rate and
conduction
Increased serum digoxin
levels, increased risk of
toxicity
Monitor serum
potassium and correct
hypokalaemia
Diltiazem, verapamil
Amiodarone, quinidine
Antacids, sucralfate, bile
acid binding resins
Reduced absorption of
digoxin
Monitor serum digoxin
levels and reduce dose if
necessary
Halve digoxin dose on
initiation of amiodarone
or quinidine, monitor
serum digoxin levels and
allow for long half-life
of amiodarone
Separate doses by at
least 2 hours
Is the drug effect and/or side effects
monitored appropriately?
Diuretic
▲ Monitor clinical status and electrolytes to avoid
volume depletion and electrolyte disturbance7.
Monitor potassium and magnesium, renal
function, blood pressure and daily weight.
potassium sparing diuretic or potassium
supplement should be added2. Low doses of
potassium sparing diuretic may be more effective
than a potassium supplement1. In patients with
renal impairment hypokalaemia rarely occurs.
Digoxin
▲ Monitor serum digoxin levels, serum potassium
and renal function to avoid toxicity2.
ACE inhibitor
▲ Monitor blood pressure, renal function and
electrolytes. A significant increase in serum
creatinine occurs in up to 30% of patients with
heart failure treated with an ACE inhibitor.
ACE inhibitor and loop diuretic
▲ In patients with normal renal function,
hypokalaemia occasionally occurs and a
Action/Plan
Changing therapy
Increasing and maintaining the dose of an ACE
inhibitor
▲ Ensure the patient is not volume depleted before
increasing the dose. Increase the dose in small
increments. Check blood pressure, renal function
and electrolytes after each increase in dose4.
Consider lowering the dose of diuretic at each
increase in dose of ACE inhibitor.
▲ Maintain long term therapy even if symptoms do
not improve.
Adding a new therapy
Commencing an ACE inhibitor
▲ The GP can initiate an ACE inhibitor and titrate
therapy with careful monitoring in the first few
weeks of therapy. (See Table 3 for “high risk”
patients who should be referred for specialist care).
▲ Start at very low doses (see Table 1) to avoid
hypotension and increase the dose gradually over
2-3 weeks3.
Are there problems with
compliance/concordance?
Discuss with the patient how medications are taken
and any problems with supply, administration or side
effects. Ensure that the patient understands the goals
of therapy and their current medication regimen
including life long use of ACE inhibitor therapy.
▲ Withhold loop diuretics for at least 24 hours on
initiation of ACE inhibitor7, in those taking high
doses reduce the dose several days before
commencing and correct any hypovolaemia.
Withhold or reduce the dose of thiazide diuretics
for at least 24 hours. Avoid potassium sparing
diuretics (eg spironolactone) during initiation of
therapy.
▲ If possible, start treatment in the evening, when
supine, to minimise potential hypotensive effects.
Otherwise, observation of the patient for a few
hours after the first dose is advisable3. Use caution
in the elderly to avoid falls.
▲ Monitor blood pressure, renal function and
electrolytes prior to and approximately one week
after initiating therapy and after each significant
increase in dose4. When stable, monitor renal
function and electrolytes at 6-12 month intervals3.
▲ If symptomatic hypotension, hyperkalaemia or a
significant deterioration in renal function occurs
(eg a serum creatinine rise of over 0.05mmol/L4),
treatment should be modified. Renal function will
often improve if the dose of concomitant diuretic
therapy is reduced1.
▲ Symptomatic improvement may not be seen for
weeks or months after initiation of an ACE
inhibitor.
...continued on back page
Table 3 - “High-risk” patients with any of the following should be referred for specialist
care3 when commencing an ACE inhibitor
▲ cause of heart failure unknown
▲ serum sodium < 130mmol/L
▲ systolic blood pressure < 100mmHg
▲ moderate or severe heart failure
▲ serum creatinine > 0.13mmol/L (note - British
▲ valve disease.
guidelines4 suggest creatinine >0.15mmol/L)
5
Action/Plan
...continued
Commencing a diuretic
Commencing spironolactone
▲ Monitor serum electrolytes, serum urate and
▲ In severe heart failure when symptoms continue
(despite ACE inhibitor and loop diuretic
therapy) in the patient with normal serum
potassium and renal function, initiate
spironolactone at 25mg each morning, increased
to 50mg daily if tolerated. Monitor serum
potassium closely.
renal function 3-6 weeks after starting thiazide
therapy.
▲ Loop diuretics carry a higher risk of electrolyte
disturbances. Monitor serum electrolytes, renal
function and urate one week after starting
therapy and repeat periodically every 3-6 weeks.
▲ If serum potassium increases to >5.5mmol/L,
▲ If potassium supplementation is necessary,
reduce dose of spironolactone to 25mg every
second day.
consider the use of spironolactone. If
hypokalaemia is difficult to correct it may
indicate low total body magnesium levels.
References:
1. Advisory Council to Improve Outcomes Nationwide in Heart Failure. Consensus recommendations for the management of chronic
heart failure. Am J Cardiol 1999;82(2A):1A-38A
2. Therapeutic Guidelines: Cardiovascular 3rd ed, Melbourne: June 1999.
3. Task Force of the Working Group on Heart Failure of the European Society of Cardiology. The treatment of heart failure. Eur Heart
Journal 1997;18:736-753
4. Eccles M, Freemantle N, Mason J, for the North of England Guideline Develoment Group. North of England evidence based project:
guideline for angiotensin converting enzyme inhibitors in primary care management of adults symptomatic heart failure. BMJ
1998;316:1369-1375
5. European Society of Cardiology Congress Symposium. Saving Lives in Heart Failure: Outcome Trials with ACE inhibitors, Vienna, Aug
1998.
6. Pitt B, Zannad F, Remme WJ, Cody R, Castaigne A et al. The effect of spironolactone on morbidity and mortality in patients with
severe heart failure. N Engl J Med 1999;341:709-17
7. Australian Medicines Handbook 2000. Adelaide 2000
8. The Digitalis Investigation Group. The effect of digoxin on mortality and morbidity in patients with heart failure. N Engl J Med
1997;336:525-533
The information contained in this material is derived from a critical analysis of a wide range of authoritative evidence.
Any treatment decisions based on this information should be made
in the context of the individual clinical circumstances of each patient.
N P S
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