Practical recommendations for the use of ACE inhibitors, beta-blockers and spironolactone in heart failure: Putting Guidelines into Practice

1
Practical recommendations for the use of ACE
inhibitors, beta-blockers and spironolactone in
heart failure Putting Guidelines into
Practice INTRODUCTION

• McMurray J, Cohen-Solal A, Dietz R, Eichhorn
  E, Erhardt L, Hobbs R, Maggioni A, Pina I,
  Soler-Soler J, Swedberg K Eur J Heart
  Failure 20013495502

2
Practical Recommendations for Heart Failure
Treatment Putting Guidelines into Practice
INTRODUCTION

• A number of large, carefully designed clinical
  outcome trials have been
• conducted in patients with chronic heart failure
• The trials were sufficiently powered to allow
  unequivocal interpretation
• of the results
• Consequently, there now exists robust safety and
  efficacy information
• on a number of therapeutic interventions
• The translation of these results into clinical
  prescribing has been
• slow and incomplete
• Patients may therefore be denied the full benefit
  of proven
• therapeutic interventions

3
Practical Recommendations for Heart Failure
Treatment Putting Guidelines into Practice
INTRODUCTION

• Development of Recommendations
• The speed and extent of update of evidence-based
  therapies (particularly ACE inhibitors and
  beta-blockers) for the treatment of heart failure
  has been disappointing in hospital practice and
  primary care
• This may reflect a lack of practical advice
  regarding dosing issues and the management of
  associated adverse events
• Consequently, a group of eminent clinicians with
  expertise in the management of heart failure met
  during 2000
• The remit of the faculty was to review all the
  relevant published clinical trials and produce a
  set of clinical recommendations independent of
  any other interests

4
Practical Recommendations for in Heart Failure
Treatment Putting Guidelines into Practice
INTRODUCTION

• Advisory Group
• John McMurray Glasgow, UK
• Alain Cohen-Solal Clichy, France
• Rainer Dietz Berlin, Germany
• Eric Eichhorn Dallas, USA
• Leif Erhardt Malmö, Sweden
• Richard Hobbs Birmingham, UK
• Aldo Maggioni Florence, Italy
• Ileana Pina Cleveland, USA
• Jordi Soler-Soler Barcelona, Spain
• Karl Swedberg Göteborg, Sweden

5
Practical Recommendations for Heart Failure
Treatment Putting Guidelines into Practice
INTRODUCTION

• Output
• The output from discussions was a step-wise,
  concise set of clinical recommendations
  concentrating on three key therapies for the
  management of heart failure
• These recommendations are not meant to replace
  existing guidelines, but rather provide a tool to
  facilitate their implementation
• The opinions expressed are those of the faculty
  members and do not necessarily reflect the views
  of AstraZeneca or the manufacturers of the
  products mentioned
• Prescribers need to be aware of the relevant
  product prescribing information which applies in
  their country
• The costs associated with the Advisory Group
  meetings were met by an educational grant from
  AstraZeneca

6
Practical Recommendations for Heart Failure
Treatment Putting Guidelines into Practice
INTRODUCTION

• Format
• The practical recommendations for treatment are
  reviewed under the
• following headings
• Why? what evidence exists to support the use of
  these treatments
• In whom and when? which patients, what
  contra-indications, what cautions and drug
  interactions
• Where? hospital or primary care setting
• Which agent and what dose? options offered
  based on outcome evidence
• How to use titration and monitoring information
• Advice to patient expected benefits and
  drawbacks
• Problem solving management of adverse events
  and concomitant medications

7
Practical Recommendations for Heart Failure
Treatment Putting Guidelines into Practice
INTRODUCTION

• Practical Recommendations
• These recommendations start from the assumption
  that the physician has made
• a clinical diagnosis of heart failure and may
  have initiated diuretic treatment for
• treating the symptoms and signs associated with
  fluid overload
• STEP 1
• - Confirm left ventricular systolic dysfunction
  (LVSD) by echocardiography, radionuclide
  ventriculography or radiological left ventricular
  angiography. These investigations are
  regarded as definitive and must be regarded as
  representing the minimum standard of care.

8
Practical Recommendations for Heart Failure
Treatment Putting Guidelines into Practice
INTRODUCTION

• Practical Recommendations
• STEP 2
• - Initiate first-line therapy in all
  patients with heart failure due to LVSD with an
  ACE inhibitor for NYHA class I-IV and a
  beta-blocker for NYHA class II-III, unless these
  are contra-indicated.
• - Initiate ACE inhibitor first, followed by
  beta-blocker, both initially at low doses and
  then up-titrate slowly to the target doses used
  in the clinical trials, check tolerability and
  blood chemistry.
• STEP 3
• - Initiate second-line therapy in patients with
  persistent signs and symptoms of heart failure
  (NYHA class III/IV) with spironolactone and
  digoxin contra-indications and cautions should
  be observed.
• - Initiate spironolactone first followed by
  digoxin, both at a low dose and then up-
  titrate, check tolerability and blood chemistry.

9
Practical Recommendations for Heart Failure
Treatment Putting Guidelines into Practice
INTRODUCTION

• The preparation of these concise and practical
  clinical recommendations for the prescribing of
  ACE inhibitors and beta-blockers should provide
  doctors with the confidence to practise
  evidence-based medicine in their patients with
  chronic heart failure. This would improve not
  only the outcomes for the individual patient but
  also reduce the burden on healthcare systems.
• McMurray J, Cohen-Solal A, Dietz R, Eichhorn E,
  Erhardt L,
• Hobbs R, Maggioni A, Pina I, Soler-Soler J,
  Swedberg K
• Eur J Heart Failure 20013495502

10
Practical recommendations for the use of ACE
inhibitors, beta-blockers and spironolactone in
heart failure Putting Guidelines into Practice
ACE INHIBITORS

• McMurray J, Cohen-Solal A, Dietz R, Eichhorn E,
  Erhardt L, Hobbs R, Maggioni A, Pina I,
  Soler-Soler J, Swedberg K Eur J Heart
  Failure 20013495502

11
Practical Recommendations for Heart Failure
Treatment Putting Guidelines into Practice
ACE INHIBITORS

• Format
• The practical recommendations for treatment are
  reviewed under the
• following headings
• Why? what evidence exists to support the use of
  these treatments
• In whom and when? which patients, what
  contra-indications, what cautions and drug
  interactions
• Where? hospital or primary care setting
• Which agent and what dose? options offered
  based on outcome evidence
• How to use titration and monitoring information
• Advice to patient expected benefits and
  drawbacks
• Problem solving management of adverse events
  and concomitant medications

12
Practical Recommendations for Heart Failure
Treatment Putting Guidelines into Practice
ACE INHIBITORS

• ACE Inhibitors Why?
• CONSENSUS I, the SOLVD-treatment study and a
  meta-analysis of smaller trials showed
  conclusively that ACE inhibitors increase
  survival, reduce hospital admissions and improve
  NYHA class and quality of life in patients with
  all grades of symptomatic heart failure
• ATLAS showed clinically important advantages with
  higher doses of ACE inhibitors in heart failure
• SAVE, AIRE and TRACE showed that ACE inhibitors
  increase survival in patients with systolic
  dysfunction after acute myocardial infarction
• SOLVD-prevention study showed that ACE inhibitors
  delay or prevent the development of symptomatic
  heart failure in patients with asymptomatic LVSD

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Practical Recommendations for Heart Failure
Treatment Putting Guidelines into Practice
ACE INHIBITORS

• Co-operative North Scandinavian Enalapril
  Survival Study I CONSENSUS I
• CONSENSUS Trial Study Group N Engl J Med
  198731614291435

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Practical Recommendations for Heart Failure
Treatment Putting Guidelines into Practice
ACE INHIBITORS

• Studies of Left Ventricular Dysfunction SOLVD
  (Treatment Study)
• SOLVD Investigators N Engl J Med
  1991325293302

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Practical Recommendations for Heart Failure
Treatment Putting Guidelines into Practice
ACE INHIBITORS

• Assessment of Treatment with Lisinopril and
  Survival Study ATLAS
• Event-
• free
• survival High-dose
• Low-dose

Combined all-cause mortality plus all-cause
hospitalisations
Risk reduction 12 p0.002
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Practical Recommendations for Heart Failure
Treatment Putting Guidelines into Practice
ACE INHIBITORS

• ACE Inhibitors In Whom and When?
• Indications
• Potentially all patients with heart failure
• First-line treatment (along with beta-blockers)
  in NYHA class IIV heart failure
• Contra-indications
• History of angioneurotic oedema
• Cautions/seek specialist advice
• Significant renal dysfunction (creatinine gt2.5
  mg/dL or 221 µmol/L) or hyperkalaemia (K gt5.0
  mmol/L)
• Symptomatic or severe asymptomatic hypotension
  (SBP lt90 mmHg)
• Drug interactions to look out for
• K supplements/ K sparing diuretics (including
  spironolactone)
• NSAIDs
• AT1-receptor blockers avoid unless essential

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Practical Recommendations for Heart Failure
Treatment Putting Guidelines into Practice
ACE INHIBITORS

• ACE Inhibitors Where?
• In the community for most patients
• Exceptions see CAUTIONS/SPECIALIST ADVICE

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Practical Recommendations for Heart Failure
Treatment Putting Guidelines into Practice
ACE INHIBITORS

• ACE Inhibitors Which and What Dose?
• Starting dose Target dose
• captopril 6.25 mg tds 50100 mg tds
• enalapril 2.5 mg bd 1020 mg bd
• lisinopril 2.55 mg od 3035 mg od
• ramipril 2.5 mg od 5 mg bd/10 mg od
• trandolapril 1 mg od 4 mg od
• od once daily bd twice daily tds
  thrice daily

19
Practical Recommendations for Heart Failure
Treatment Putting Guidelines into Practice
ACE INHIBITORS

• ACE Inhibitors How to Use
• Start with a low dose
• Double dose at not less than two weekly
  intervals
• Aim for target dose or, failing that, the highest
  tolerated dose
• Remember some ACE inhibitor is better than no ACE
  inhibitor
• Monitor blood chemistry (urea, creatinine, K)
  and blood pressure
• When to stop up-titration/down-titration see
  PROBLEM SOLVING

20
Practical Recommendations for Heart Failure
Treatment Putting Guidelines into Practice
ACE INHIBITORS

• ACE Inhibitors Advice to Patient
• Explain expected benefits (see WHY?)
• Treatment is given to improve symptoms, to
  prevent worsening of heart failure and to
  increase survival
• Symptoms improve within a few weeks to a few
  months
• Advise patients to report principal adverse
  effects
• (i.e. dizziness/symptomatic hypotension, cough)

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Practical Recommendations for Heart Failure
Treatment Putting Guidelines into Practice
ACE INHIBITORS

• ACE Inhibitors Problem Solving
• Asymptomatic low blood pressure
• Does not usually require any change in therapy
• Symptomatic hypotension
• If dizziness, light-headedness and/or confusion
  and low blood pressure occur, reconsider need for
  nitrates, calcium channel blockers and other
  vasodilators
• If no signs/symptoms of congestion, consider
  reducing diuretic dose
• If these measures do not solve the problem, seek
  specialist advice
• calcium channel blockers should be discontinued
  unless absolutely essential (e.g. for angina or
  hypertension)

22
Practical Recommendations for Heart Failure
Treatment Putting Guidelines into Practice
ACE INHIBITORS

• ACE Inhibitors Problem Solving (continued)
• Cough
• Cough is common in patients with heart failure,
  many of whom have smoking-related lung disease
• Cough is also a symptom of pulmonary oedema,
  which should be excluded if a new or worsening
  cough develops
• ACE inhibitor-induced cough rarely requires
  treatment discontinuation
• If a very troublesome cough develops (e.g. one
  stopping the patient sleeping) and can be
  proven to be due to ACE inhibition (i.e. it
  recurs after ACE inhibitor withdrawal and
  rechallenge), substitution with an AT1-receptor
  blocker can be considered

23
Practical Recommendations for Heart Failure
Treatment Putting Guidelines into Practice
ACE INHIBITORS

• ACE Inhibitors Problem Solving (continued)
• Worsening renal function
• Some increase in urea (blood urea nitrogen),
  creatinine and K is to be expected after
  initiation if the increase is small and
  asymptomatic no action is necessary
• An increase in creatinine of up to 50 above
  baseline, or 3 mg/dL (266 µmol/L), whichever is
  the smaller, is acceptable
• An increase in K ? 6.0 mmol/L is acceptable
• If urea, creatinine or K rise excessively,
  consider stopping concomitant nephrotoxic drugs
  (e.g. NSAIDs), other K supplements/ K retaining
  agents (triamterene, amiloride) and, if no signs
  of congestion, reducing the dose of diuretic
• If greater rises in creatinine or K than those
  outlined above persist, despite adjustment of
  concomitant medications, halve the dose of ACE
  inhibitor and recheck blood chemistry if there
  is still an unsatisfactory response, specialist
  advice should be sought

24
Practical Recommendations for Heart Failure
Treatment Putting Guidelines into Practice
ACE INHIBITORS

• ACE Inhibitors Problem Solving (continued)
• Worsening renal function (cont.)
• If K rises to gt6.0 mmol/L, or creatinine
  increases by gt100 or to above 4 mg/dL (354
  µmol/L), the dose of ACE inhibitor should be
  stopped and specialist advice sought
• Blood chemistry should be monitored serially
  until K and creatinine have plateaued
• NOTE it is very rarely necessary to stop an ACE
  inhibitor and clinical deterioration is likely
  if treatment is withdrawn ideally, specialist
  advice should be sought before treatment
  discontinuation

25
Practical Recommendations for Heart Failure
Treatment Putting Guidelines into Practice
AT1-RECEPTOR BLOCKERS

• AT1-Receptor Blockers
• At present, position is unclear due to
  inconclusive evidence from clinical trials
  (ELITE I, ELITE II, Val-HeFT)
• Currently, prescribing AT1-receptor blockers in
  heart failure should be confined to
  patients who are unable to tolerate ACE
  inhibitors
• Results from the ongoing CHARM study programme,
  involving candesartan, should provide a
  clearer picture of their role in heart failure
  management

26
Practical recommendations for the use of ACE
inhibitors, beta-blockers and spironolactone in
heart failure Putting Guidelines into Practice
BETA BLOCKERS

• McMurray J, Cohen-Solal A, Dietz R, Eichhorn E,
  Erhardt L, Hobbs R, Maggioni A, Pina I,
  Soler-Soler J, Swedberg K Eur J Heart
  Failure 20013495502

27
Practical Recommendations for Heart Failure
Treatment Putting Guidelines into Practice
BETA BLOCKERS

• Format
• The practical recommendations for treatment are
  reviewed under the
• following headings
• Why? what evidence exists to support the use of
  these treatments
• In whom and when? which patients, what
  contra-indications, what cautions and drug
  interactions
• Where? hospital or primary care setting
• Which agent and what dose? options offered
  based on outcome evidence
• How to use titration and monitoring information
• Advice to patient expected benefits and
  drawbacks
• Problem solving management of adverse events
  and concomitant medications

28
Practical Recommendations for Heart Failure
Treatment Putting Guidelines into Practice
BETA BLOCKERS

• Beta Blockers Why?
• USCP, CIBIS II, MERIT-HF and COPERNICUS have
  shown conclusively that beta-blockers
  increase survival, reduce hospital admissions and
  improve NYHA class and quality of life when
  added to standard therapy (diuretics, digoxin and
  ACE inhibitors) in patients with stable
  mild and moderate heart failure and in
  some patients with severe heart failure
• One trial (BEST) did not show a reduction in
  all-cause mortality but did report a reduction in
  cardiovascular mortality

29
Practical Recommendations for Heart Failure
Treatment Putting Guidelines into Practice
BETA BLOCKERS

• United States Carvedilol Program (USCP)
• Packer M et al. N Engl J Med
  199633413491355

30
Practical Recommendations for Heart Failure
Treatment Putting Guidelines into Practice
BETA BLOCKERS

• Cardiac Insufficiency Bisoprolol Study II
  (CIBIS II)
• CIBIS II Investigators, Lancet
  1999359913

31
Practical Recommendations for Heart Failure
Treatment Putting Guidelines into Practice
BETA BLOCKERS

• Metoprolol CR/XL Randomized Intervention Trial in
  Congestive Heart Failure (MERIT-HF)
• Hjalmarson A et al. Lancet 199935320012007

32
Practical Recommendations for Heart Failure
Treatment Putting Guidelines into Practice
BETA BLOCKERS

• Beta Blockers In Whom and When?
• Indications
• Potentially all patients with stable mild and
  moderate heart failure patients with
  severe heart failure should be referred for
  specialist advice
• First-line treatment (along with ACE inhibitors)
  in patients with stable NYHA class IIIII
  heart failure start as early as possible
• Contra-indications
• Asthma

33
Practical Recommendations for Heart Failure
Treatment Putting Guidelines into Practice
BETA BLOCKERS

• Beta Blockers In Whom and When? (continued)
• Cautions/seek specialist advice
• Severe (NYHA Class IV) heart failure
• Current or recent (lt4 weeks) exacerbation of
  heart failure (e.g. hospital admission with
  worsening heart failure)
• Heart block or heart rate lt60 beats/min
• Persisting signs of congestion raised jugular
  venous pressure, ascites, marked peripheral
  oedema
• Drug interactions to look out for
• verapamil/diltiazem (should be discontinued)
• amiodarone

34
Practical Recommendations for Heart Failure
Treatment Putting Guidelines into Practice
BETA BLOCKERS

• Beta Blockers Where?
• In the community in stable patients (NYHA class
  IV/severe heart failure patients should be
  referred for specialist advice)
• Not in unstable patients hospitalised with
  worsening heart failure
• Other exceptions see CAUTIONS/SEEK SPECIALIST
  ADVICE

35
Practical Recommendations for Heart Failure
Treatment Putting Guidelines into Practice
BETA BLOCKERS

• Beta Blockers Which and What Dose?
• Starting dose Target dose
• bisoprolol 1.25 mg od 10 mg od
• carvedilol 3.125 mg bd 2550 mg bd
• metoprolol CR/XL 12.525 mg od
  200 mg od
• od once daily bd twice daily

36
Practical Recommendations for Heart Failure
Treatment Putting Guidelines into Practice
BETA BLOCKERS

• Beta Blockers How to Use
• Start with a low dose
• Double dose at not less than two-weekly intervals
• Aim for target dose or, failing that, the highest
  tolerated dose
• Remember some beta-blocker is better than no
  beta-blocker
• Monitor HR, BP, clinical status (symptoms, signs
  especially signs of congestion, and body
  weight)
• Check blood chemistry 12 weeks after initiation
  and 12 weeks after final dose titration
• A specialist heart failure nurse may assist with
  patient education, follow-up (in
  person/by telephone) and dose up-titration
• When to down-titrate/stop up-titration see
  PROBLEM SOLVING

37
Practical Recommendations for Heart Failure
Treatment Putting Guidelines into Practice
BETA BLOCKERS

• Beta Blockers Advice to Patient
• Explain expected benefits (see WHY?)
• Emphasise that treatment given as much to prevent
  worsening of heart failure as to
  improve symptoms beta-blockers also increase
  survival
• If symptomatic improvement occurs, this may
  develop slowly, 36 months or longer
• Temporary symptomatic deterioration may occur
  (estimated 2030 of cases) during
  initiation/up-titration phase

38
Practical Recommendations for Heart Failure
Treatment Putting Guidelines into Practice
BETA BLOCKERS

• Beta Blockers Advice to Patient (continued)
• Advise patient to report deterioration (see
  PROBLEM SOLVING) and that deterioration
  (tiredness, fatigue, breathlessness) can usually
  be easily managed by adjustment of other
  medication patients should be advised not to
  stop beta-blocker therapy without
  consulting their physician
• Patients should be encouraged to weigh themselves
  daily (after waking, before dressing, after
  voiding, before eating) and to increase their
  diuretic dose should their weight increase,
  persistently (gt2 days), by gt1.52.0 kg

39
Practical Recommendations for Heart Failure
Treatment Putting Guidelines into Practice
BETA BLOCKERS

• Beta Blockers Problem Solving
• Worsening symptoms/signs (e.g. increasing
  dyspnoea,
• fatigue, oedema, weight gain)
• If increasing congestion, double the dose of
  diuretic and/or halve the dose of beta-blocker
  (if increasing diuretic does not work)
• If marked fatigue (and/or bradycardia see
  below), halve the dose of beta-blocker (rarely
  necessary)
• Review patient in 12 weeks if not improved,
  seek specialist advice
• If serious deterioration, halve the dose of
  beta-blocker or stop this treatment (rarely
  necessary) seek specialist advice

40
Practical Recommendations for Heart Failure
Treatment Putting Guidelines into Practice
BETA BLOCKERS

• Beta Blockers Problem Solving (continued)
• Low heart rate
• If lt50 beats/min and worsening symptoms halve
  the dose of beta-blocker or, if
  severe deterioration, stop beta-blocker (rarely
  necessary)
• Review need for other heart-rate slowing drugs
  (e.g. digoxin, amiodarone, diltiazem)
• Arrange ECG to exclude heart block
• Seek specialist advice

41
Practical Recommendations for Heart Failure
Treatment Putting Guidelines into Practice
BETA BLOCKERS

• Beta Blockers Problem Solving (continued)
• Asymptomatic low blood pressure
• Does not usually require any change in therapy
• Symptomatic hypotension
• If dizziness, light-headedness and/or confusion
  and a low blood pressure occur, reconsider need
  for nitrates, calcium channel blockers and other
  vasodilators
• If no signs/symptoms of congestion, consider
  reducing diuretic dose
• If these measures do not solve problem, seek
  specialist advice
• NOTE Beta-blockers should not be stopped
  suddenly unless absolutely necessary (there is
  a risk of a rebound increase in myocardial
  ischaemia/infarction and arrhythmias) ideally
  specialist advice should be sought before
  treatment discontinuation

42
Practical recommendations for the use of ACE
inhibitors, beta-blockers and spironolactone in
heart failure Putting Guidelines into
Practice SPIRONOLACTONE

• McMurray J, Cohen-Solal A, Dietz R, Eichhorn E,
  Erhardt L, Hobbs R, Maggioni A, Pina I,
  Soler-Soler J, Swedberg K Eur J Heart
  Failure 20013495502

43
Practical Recommendations for Heart Failure
Treatment Putting Guidelines into Practice
SPIRONOLACTONE

• Format
• The practical recommendations for treatment are
  reviewed under the
• following headings
• Why? what evidence exists to support the use of
  these treatments
• In whom and when? which patients, what
  contra-indications, what cautions and drug
  interactions
• Where? hospital or primary care setting
• Which agent and what dose? options offered
  based on outcome evidence
• How to use titration and monitoring information
• Advice to patient expected benefits and
  drawbacks
• Problem solving management of adverse events
  and concomitant medications

44
Practical Recommendations for Heart Failure
Treatment Putting Guidelines into Practice
SPIRONOLACTONE

• Spironolactone Why?
• The RALES study showed that low-dose
  spironolactone increased survival, reduced
  hospital admissions and improved NYHA class when
  added to standard therapy (diuretic, digoxin, ACE
  inhibitor and, in a minority of cases, a
  beta-blocker) in patients with severe (NYHA class
  III or IV) heart failure

45
Practical Recommendations for Heart Failure
Treatment Putting Guidelines into Practice
SPIRONOLACTONE

• Pitt B et al. N Engl J Med 199910709717

46
Practical Recommendations for Heart Failure
Treatment Putting Guidelines into Practice
SPIRONOLACTONE

• Spironolactone In Whom and When?
• Indications
• Potentially all patients with symptomatically
  moderately severe or severe heart failure
• Second-line therapy (after ACE inhibitors and
  beta-blockers) in patients with NYHA class IIIIV
  heart failure
• Cautions/seek specialist advice
• Significant renal dysfunction (creatinine gt221
  µmol/L or 2.5 mg/dL)
• Significant hyperkalaemia (K gt5.0 mmol/L)

47
Practical Recommendations for Heart Failure
Treatment Putting Guidelines into Practice
SPIRONOLACTONE

• Spironolactone In Whom and When? (Continued)
• Drug interactions to look out for
• ACE inhibitors, AT1-receptor blockers, other K
  sparing diuretics (beware combination
  preparations, e.g. frusemide plus amiloride or
  triamterene), K supplements (e.g.
  KCl)
• NSAIDs
• Low salt substitutes with high K content

48
Practical Recommendations for Heart Failure
Treatment Putting Guidelines into Practice
SPIRONOLACTONE

• Spironolactone Where?
• In the community or in hospital
• Exceptions see CAUTIONS/SEEK SPECIALIST ADVICE
  
• Spironolactone Which Dose?
• Starting dose 25 mg od or on alternate days
• Target dose 2550 mg od

49
Practical Recommendations for Heart Failure
Treatment Putting Guidelines into Practice
SPIRONOLACTONE

• Spironolactone How to Use
• Start at 25 mg once daily
• Check blood chemistry at 1, 4, 8 and 12 weeks 6,
  9 and 12 months 6
  monthly thereafter
• If K rises to between 5.5 and 6.0 mmol/L, or
  creatinine rises to 2.5 mg/dL (221
  µmol/L), reduce dose to 25 mg on alternate days
  and monitor blood chemistry closely
• If K rises to gt6.0 mmol/L, or creatinine to gt4.0
  mg/dL (354 µmol/L), stop spironolactone and seek
  specialist advice

50
Practical Recommendations for Heart Failure
Treatment Putting Guidelines into Practice
SPIRONOLACTONE

• Spironolactone Advice to Patient
• Explain expected benefits (see WHY?)
• Treatment is given to improve symptoms, prevent
  worsening of heart failure and to
  increase survival
• Symptom improvement occurs within a few weeks to
  a few months of starting treatment
• Avoid NSAIDs not prescribed by a physician
  (self-purchased over the counter treatment,
  e.g. ibuprofen)
• Temporarily stop spironolactone if diarrhoea
  and/or vomiting occur and contact physician

51
Practical Recommendations for Heart Failure
Treatment Putting Guidelines into Practice
SPIRONOLACTONE

• Spironolactone Problem Solving
• Worsening renal function/hyperkalaemia
• See HOW TO USE section
• Major concern is hyperkalaemia (K gt6.0 mmol/L)
  though this was uncommon in RALES a high-normal
  K may be desirable in heart failure patients,
  especially if taking digoxin
• It is important to avoid other K retaining drugs
  (e.g. K sparing diuretics) and nephrotoxic
  agents (e.g. NSAIDs)
• Some low salt substitutes have a high K
  content
• Male patients may develop breast discomfort
  and/or gynaecomastia