Beta-blockers: take the next step for heart failure

Heart failure is a common reason for attendance at general practitioner clinics. It affects 4% of Australians (aged 45 years or more)¹ with the prevalence increasing from about 1% at age 50 to 59 years, to over 50% above age 84². Heart failure is likely to be prevalent amongst veterans of whom 82% are over 65 years of age³.

The management of patients with heart failure is increasing in the primary care setting, and the emphasis of new national programs on early recognition of signs and diagnosis of heart failure suggest that this trend will continue⁴.

The focus of this second module of the Veterans’ MATES program is on recent evidence for the role of beta-blockers in managing heart failure. This module will address how to initiate and monitor beta-blockers, particularly in the primary care setting, as well as concerns about adverse effects, contraindications and co-morbidities.

Evidence for beta-blockers in heart failure

Patients who have mild symptoms or who appear clinically stable may not seem to require additional treatment. These patients are however at high risk for morbidity and mortality and are likely to deteriorate during the ensuing 12 months even if treated with loop diuretics⁵ and ACE inhibitors with or without digoxin. Therefore, even if they do not benefit symptomatically because they have little disability, patients with mild symptoms should receive treatment with a beta-blocker to reduce the risk from disease progression, future clinical deterioration and sudden death⁶.

Gradual up-titration of beta-blockers improves left ventricular function and reduces risk of death and hospitalisation for patients with all grades of systolic heart failure^2,6,7. These benefits are in addition to those achieved with ACE inhibitors^2,6,7.

To obtain these additional benefits it is recommended that you take the next step in managing your veteran’s heart failure by considering the careful addition of a beta-blocker after achieving the highest tolerated dose of an ACE inhibitor.

Who will benefit from beta-blockers?

Beta-blockers are recommended therapy, unless not tolerated or contraindicated^a, for all patients with systolic heart failure in addition to appropriate doses of ACE inhibitors^b and loop diuretics (commonly used for heart failure of moderate severity).^5,6,8

The benefits of beta-blockers in heart failure are also seen in patients with co-existent diabetes mellitus. Close monitoring of blood glucose levels is essential.^6,9

Beta-blockers are also recommended for patients with symptoms of advanced heart failure².

Beta-blockers should not be initiated during a phase of acute heart failure but only after the patient’s condition has stabilised².

Patients who are already taking a beta-blocker for a concomitant condition such as angina or hypertension may be changed to one approved for the treatment of heart failure, or the beta-blocker already prescribed may be continued⁸.

For patients who have previously tried a beta-blocker for another condition, and discontinued it because of minor adverse effects, consider re-starting beta-blocker therapy with an agent approved for heart failure unless contraindicated.^6,8

^a See below for pre-existing conditions where specialist management may be indicated.

^b Information on appropriate doses of ACE inhibitors is available in Therapeutic Guidelines, Cardiovascular or the Australian Medicines Handbook.

Initiating beta-blockers

Start low and go slow:

• Commence with the low dose specified in Table 1.
• Increase the dose gradually to the highest tolerated dose (target doses and dose titration intervals schedules appear in Table 1).

The schedules outline minimum recommended titration intervals. The rate of dosage increase may need to be slower in the veteran population.

Table 1: Dosage recommendations of beta-blockers approved to treat heart failure in Australia^c

Beta Blocker	Starting Dose	Up-Titration	Target Dose
Bisoprolol (Bicor®)	1.25 mg once daily for one week;	Increase dose if tolerated: 2.5 mg once daily for one week, then 3.75 mg once daily for one week, then 5 mg once daily for four weeks, then 7.5 mg once daily for four weeks	10 mg once daily
Carvedilol (Dilatrend®, Kredex®)	3.125 mg twice daily for two weeks	Increase dose if tolerated: at intervals of at least two weeks to 6.25 mg twice daily, then 12.5 mg twice daily	25 mg twice daily (in patients <85 kg with mild to moderate heart failure and in all patients with severe heart failure) or 50 mg twice daily (in patients >85 kg
Metoprolol succinate controlled-release (Toprol-XL®)	23.75 mg* once daily for two weeks	Increase dose if tolerated: at intervals of at least two weeks to 47.5 mg daily, then 95 mg daily	190 mg daily.

^* If NYHA Class III-IV - initiate at half a 23.75 mg tablet once daily for one week then a full 23.75 mg tablet once daily for the second week

^c Adapted from NPS NEWS 36 with permission.

Monitoring and review^6,8,10

• Monitor heart rate, blood pressure and clinical signs and symptoms of heart failure on a weekly basis during dose titration.
• Advise your patients to weigh themselves daily, preferably each morning before dressing. Changes of >1.5kg in 24 hours may indicate problems.

Managing adverse effects^6,8

Adverse effects are often transient and interventions may only need to be temporary.

Low BP

If asymptomatic hypotension is present, usually no change in therapy is required. If hypotension causes dizziness, light headedness or confusion, consider the effects of drugs that may lower blood pressure e.g. diltiazem, prazosin, tricyclic antidepressants. Diuretic dose may require adjustment.

Heart Rate <50 beats/minute

If the heart rate is <50 bpm an ECG should be performed even if the patient is asymptomatic. The dose of beta-blocker should be reduced if there is symptomatic bradycardia. Review the need to continue treatment with other drugs that may slow heart rate e.g. verapamil, diltiazem, digoxin and amiodarone. If unsure, consult a specialist.

Increased fluid retention

Increase the dose of loop diuretic, monitoring carefully for volume depletion and electrolyte disturbances. If the response is unsatisfactory, consider reducing the dose of beta-blocker. Review the need to continue treatment with drugs that may exacerbate fluid retention e.g. non-steroidal anti-inflammatory drugs (NSAIDs).

Severe fatigue

Exclude conditions such as anaemia, depression or hypothyroidism. If persistent consider reducing the dose of beta-blocker.

Bronchospasm

Consider effects of beta-blockade upon respiratory function for patients with reversible airways disease. Monitor for deterioration and counsel patients to report increasing breathlessness and wheeze.

Beta-blockers should not be stopped abruptly unless absolutely necessary; ideally seek specialist advice before discontinuation.

For a more complete list of adverse effects refer to the Australian Medicines Handbook.¹¹

Pre-existing conditions where specialist management may be indicated^6,10

• Uncontrolled heart failure, valvular heart disease particularly aortic stenosis/ incompetence and mitral regurgitation.
• Severe heart failure requiring hospitalisation and/or intravenous diuretics
• Reversible airways disease, asthma
• Bradycardia i.e. <50 bpm
• Symptomatic hypotension
• Second or third degree heart block (unless managed with a pace maker)

Severe ischaemic heart disease may require other specialist intervention.

Medications for heart failure - summary

A summary of the drugs used in heart failure and their effects on mortality, hospitalisation and symptom improvement is presented in Table 2.

Table 2: Therapeutic outcomes of drugs used in heart failure.^d

Therapeutic Goal	Mortality reduction	Reduced hospitalisation	Symptom improvement
ACE Inhibitor (ACE-I)	+	+	+
Diuretic	−	+	+
Beta-blocker	+	+	+/−
Spironolactone*	+	+	+
Angiotensin II Receptor Blocker (ARB) instead of ACE-I **	+	+	+
ACE Inhibitor and ARB	?	+	+
Digoxin	−	+	+

^*Effect only seen in severe heart failure.

^**Use only if ACE-I absolutely contraindicated.

^d Adapted, with permission, from Table 2. Effect of medications on therapeutic goals with heart failure. Shakib S. Problems of polypharmacy. Australian Family Physician. 2002;31(2):125-27.

What to tell my veteran patient about beta-blockers

Beta-blockers delay worsening heart failure and increase survival with long-term use.^6,12

There may be a temporary worsening of symptoms (20-30% of cases) during initiation of therapy or increase in dose. Even if symptoms do not improve, continue treatment to improve prognosis.⁶

Report increased tiredness, breathlessness or wheezing, swollen feet or ankles, difficulty with exercise or a swollen abdomen to your doctor.² These may be managed by adjusting other medication.

If you feel dizzy at any time or feel that you may fall over, contact your doctor as soon as possible.

Do not stop beta-blocker therapy without advice from your doctor as this may result in worsening of your heart failure.

Weigh yourself daily and consult your doctor if there is a weight gain of >1.5kg in a 24 hour period.²

References

1. Australian Institute of Health and Welfare. Heart failure...what of the future? June 2003. Available at: http://www.aihw.gov.au/publications/aus/bulletin06/bulletin06.pdf.
2. National Heart Foundation of Australia and the Cardiac Society of Australia and New Zealand. Guidelines on the Contemporary Management of the Patient with Chronic Heart Failure in Australia. 2002. Available at: http://www.heartfoundation.com.au/downloads/cont.management.pdf.
3. Department of Veterans’ Affairs. Survey of veterans, war widows and their carers. Canberra: DVA; 2003.
4. Phillips SM, Marton RL, Tofler GH. Barriers to diagnosing and managing heart failure in primary care. MJA. 2004;181(2):78-81.
5. Therapeutic Guidelines. Cardiovascular Version 4. 4 ed. Melbourne: Therapeutic Guidelines Limited; 2003.
6. American College of Cardiology and the American Heart Association. ACC/AHA Guidelines for the Evaluation and Management of Chronic Heart Failure in the Adult. Available at: www.acc.org/clinical/guidelines/failure/pdfs/hf_fulltext.pdf.
7. National Heart Foundation of New Zealand. A guideline for the management of heart failure - health professionals guide. Available at: www.nhf.org.nz/files/Cardiac_Care/heart_failure_guidelines.pdf. Accessed 10/12/2004.
8. The National Collaborating Centre for Chronic Conditions. Chronic Heart Failure: National clinical guideline for diagnosis and management in primary and secondary care. Royal College of Physicians of London,. 2003. Available at: http://www.nice.org.uk/pdf/Full_HF_Guideline.pdf.
9. Haas SJ, Gilbert RE, Krum H. Are beta-blockers as efficacious in patients with diabetes mellitus as in patients without diabetes mellitus who have chronic heart failure? A meta-analysis of large-scale clinical trials. Am Heart J. 2003;146(5):848-853.
10. Remme WJ, et al. Guidelines for the diagnosis and treatment of chronic heart failure. [erratum appears in Eur Heart J 2001 Dec;22(23):2217-8]. Eur Heart J. 2001;22(17):1527-1560.
11. Australian Medicines Handbook. Adelaide: Australian Medicines Handbook; 2004.
12. MERIT-HF Study Group, Fagerberg B. Effect of Metoprolol CR/XL in Chronic Heart Failure: Metoprolol CR/XL Randomised Intervention Trial in Congestive Heart Failure (MERIT-HF). Lancet. 1999;353:2001-2007.

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