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National Collaborating Centre for Chronic Conditions (UK). Chronic Heart Failure: National Clinical Guideline for Diagnosis and Management in Primary and Secondary Care. London: Royal College of Physicians (UK); 2003. (NICE Clinical Guidelines, No. 5.)

  • This publication is provided for historical reference only and the information may be out of date.

This publication is provided for historical reference only and the information may be out of date.

7Treating heart failure

Introduction

The aims of therapy in heart failure are to:

  • improve life expectancy
  • improve quality of life.

The relative importance of these aims will vary between individual patients, should take into account patients’ preferences, and may change with time. Clinical trials have measured achievement of these aims in different ways. Improvements in life expectancy are usually measured in terms of reductions in all-cause mortality and/or heart failure-related mortality. Improvements in quality of life have been assessed using generic measures of health status such as the Short Form-36, and through the use of more disease-specific measures, such as scoring systems that assess symptom control, ability to perform certain activities and exercise capacity. Hospitalisation rates are also often reported in clinical trials. These are relevant in that they reflect both morbidity and cost.

It may also be helpful to consider the aims of heart failure treatment in terms of the process of the delivery of care. These process-oriented aims, such as keeping patients fully informed about their condition and the treatment options, are reflected in the recommendations that appear in later sections.

Much of the evidence base for the management of heart failure relates to heart failure due to left ventricular systolic dysfunction. Although this is the most common underlying cardiac abnormality in patients with heart failure in the UK, it should not be forgotten that other cardiac abnormalities may be the cause of the heart failure – for example valve disease, or ‘diastolic’ dysfunction of the left ventricle. In some patients several abnormalities may co-exist. The evidence on which to base clinical management of these other cardiac abnormalities is much smaller than that for LV systolic dysfunction, and is covered briefly in 7.6. Specialist advice is recommended.

The guidance for the treatment of heart failure is presented under the following headings:

7.1.

Lifestyle

7.2.

Pharmacological treatment of heart failure due to LV systolic dysfunction

7.3.

Algorithm for the pharmacological treatment of symptomatic heart failure due to LV systolic dysfunction

7.4.

Invasive procedures

7.5.

Oxygen therapy and continuous positive airways pressure treatment

7.6.

Treatment of heart failure not due to LV systolic dysfunction

7.1. Lifestyle

7.1.1. Exercise training

Updated in August 2010

Inactivity can lead to physical deconditioning, which leads to a worsening of symptoms and exercise performance.45 Training can improve exercise performance – through adaptations to peripheral muscles – without adversely affecting cardiac function.46 Both aerobic exercise (such as brisk walking) and resistive exercise (such as weight training) will improve a patient’s symptoms, exercise performance and quality of life without deleterious effects on central haemodynamics.46,47 The long-term effects of exercise training (greater than a year) are not well defined. A forthcoming systematic review may clarify this (please visit www.nelh.nhs.uk/cochrane.asp). (Ia)

Breathing exercise training has been suggested to improve exercise performance.48 In one small study this yoga-derived type of respiration (a particular form of slow deep breathing) was reported to decrease breathlessness and increase oxygen saturation by about half of that found in full exercise training programmes. This has yet to be confirmed in controlled trials. (III)

Health economic evidence: There is very little economic evidence on the cost effectiveness of exercise training. Costs and benefits are specific to the particular programme adopted and it is important to consider patient borne costs, such as travel time and expenses, when considering cost effectiveness (see Appendix F).

7.1.2. Rehabilitation programmes

Updated in August 2010

The World Health Organization defined rehabilitation as the sum of the activities required to ensure the patient the best possible physical, mental and social conditions so that they may, by their own efforts, resume as normal a place as possible in the life of the community.49

Rehabilitation programmes have been shown to be effective in patients with coronary heart disease, reducing hospitalisation rates, improving quality of life, and improving exercise performance.50 It is likely that widening the remit of cardiac rehabilitation programmes to include patients with heart failure will lead to benefit for these patients, as several small RCTs have reported similar benefits to those gained by patients after myocardial infarction.50,51 (Ia)

Programmes that combine exercise, psychological support, and education, can be of greater benefit than programmes that provide only one of these components.50 Such a combined approach has also been shown to improve cardiac risk factors for patients with coronary heart disease.50 (Ia)

There are no characteristics of programme design in terms of frequency or duration that have been shown to be superior to others, and it has been suggested that the most effective regimes are those tailored to individual patients with a ‘menu’-based approach.51 (IV)

Health economic evidence: Very little is known about the health economics of rehabilitation programmes for patients with heart failure. Evidence from other disease areas suggests that if a rehabilitation programme can reduce the risk of hospitalisation they often represent a very cost effective use of resources.

RECOMMENDATIONS ON EXERCISE TRAINING AND REHABILITATION

R12.

Patients with heart failure should be encouraged to adopt regular aerobic and/or resistive exercise. This may be more effective when part of an exercise programme or a programme of rehabilitation. [B]

7.1.3. Smoking

There are no published studies of the effects of stopping smoking in patients with heart failure. Smoking has many potentially adverse effects on, for example, haemodynamics and oxygen delivery. There was consensus amongst the guideline development group that total abstinence from smoking was beneficial to the clinical status of patients with heart failure. (IV)

Counselling and education programmes can provide assistance with quitting.52,53 (Ia)

RECOMMENDATION

R13.

Patients must be strongly advised not to smoke. Referral to smoking cessation services should be considered. [GPP]

7.1.4. Alcohol

Chronic excessive alcohol consumption may damage cardiac muscle and lead to heart failure.54 Cardiac function may improve, or completely recover, in such patients if they abstain from alcohol. For patients in whom alcohol is not the cause of their heart failure, alcohol may still have clinically important effects such as precipitating arrhythmias (eg atrial fibrillation) or causing acute deterioration in cardiac function leading to clinical decompensation.55 The volume load of alcoholic beverages varies – drinking beer or lager involves a greater volume of fluid than drinking the same amount of alcohol in the form of spirits. For patients with heart failure with fluid retention that is difficult to control, this extra fluid consumption may exacerbate the problem. Many patients with heart failure, however, continue to drink alcohol without any obvious harm, and there is no evidence that alcohol should be prohibited for all patients with heart failure.51 (III)

RECOMMENDATIONS

R14.

Patients with alcohol-related heart failure should abstain from drinking alcohol. [C]

R15.

Healthcare professionals should discuss alcohol consumption with the patient and tailor their advice appropriately to the clinical circumstances. [GPP]

7.1.5. Diet and nutrition

The evidence base for diet and nutrition for patients with heart failure is limited. One small randomised trial of non-pharmacological therapy, with exercise training, dietary control, and cognitive behaviour therapy in group sessions found improvements in indices of anxiety and depression in the short term; however, potential methodological limitations to the study makes this an unreliable evidence base on which to make recommendations.56

Particular issues include:

  • Nutritional status and its assessment. Many patients with heart failure may be malnourished, but this may be partially masked by fluid retention. Assessment is not straightforward.
  • Weight reduction may be appropriate in some people with heart failure.
  • Fluid restriction is commonly advocated for those with heart failure, but this may cause dehydration in some, and may exacerbate confusion in the elderly.
  • Salt reduction is also commonly recommended by physicians to help control fluid status, but may make food less palatable.

Further research in this area is required.

7.1.6. ‘Natural’ supplementary therapies

Several supplements have been considered for treatment in heart failure, including Co-enzyme Q10, hawthorn extract, and Myrobalan (Terminalia arjuna). Neither observational nor controlled trials show evidence of benefit in terms of hospitalisation and mortality. Where trials have shown benefit they have been of poor quality57 or have small sample size.58 The mechanism of action of these therapies is not clearly understood. Studies have shown little risk of side effects or complications, although there is a potential for interactions with prescribed therapies. As supplements may be obtained without advice from a healthcare professional enquiries should be made as to the use of supplements during patient consultations (see p 63). (IIb)

Co-enzyme Q10 shows no benefit compared to placebo in terms of mortality and morbidity and the long-term safety profile is not as yet known.59–61 (Ib)

No recommendations are made.

7.1.7. Sexual activity

The systematic search did not identify any published studies of the effect of sexual activity in patients with heart failure. Breathlessness on exertion and inability to lie flat may limit activity. Patients and their partners may be concerned about the possible risk of sexual activity, and may wish guidance from a healthcare professional. There was consensus among the guideline development group that these issues should be discussed with patients and their partners, where appropriate.

Sexual intercourse increases energy expenditure by a factor of 3 to 5 in healthy men, but with a wide variation.62 Related American expert consensus guidance suggests that if a patient with coronary heart disease can achieve 5 or 6 METS on the exercise tolerance test without demonstrating arrhythmias or ischaemia electrocardiographically, they most likely are not at high risk for developing myocardial ischaemia as a result of their normal sexual activities.63 (IV)

RECOMMENDATION

R16.

Healthcare professionals should be prepared to broach sensitive issues with patients, such as sexual activity, as these are unlikely to be raised by the patient. [GPP]

7.1.8. Vaccination

There are no randomised controlled studies of vaccination against influenza in patients with heart failure. There was consensus among the guideline development group that the current UK recommendations for annual influenza vaccination for patients at high risk of developing complications from influenza infection should apply to patients with heart failure.

Patients with heart failure should also receive vaccination against pneumococcal disease (following guidance in the BNF). (IV)

RECOMMENDATIONS

R17.

Patients with heart failure should be offered an annual vaccination against influenza. [GPP]

R18.

Patients with heart failure should be offered vaccination against pneumococcal disease (only required once). [GPP]

7.1.9. Air travel

There are no pathophysiological reasons why most patients with stable heart failure and well-controlled symptoms should not be able to travel by air. Patients with decompensated heart failure, including pulmonary oedema, may become more hypoxic during air travel, and those who are symptomatic at rest or on minimal exertion may also not be fit to fly. The British Heart Foundation’s factfile on air travel states that ‘in general, if a patient can manage a flight of stairs without stopping and without significant symptoms whilst holding a conversation, he/she should be fit enough to fly… In the event of significant left ventricular dysfunction/failure flying is contra-indicated if oxygen is needed at rest on the ground.’64

For many patients the most difficult part of air travel is the long walk within the airport. Assistance may be required. (IV)

RECOMMENDATION

R19.

Air travel will be possible for the majority of patients with heart failure, depending on their clinical condition at the time of travel. [GPP]

7.1.10. Driving regulations

The Driver and Vehicle Licensing Agency (DVLA) is responsible for licensing drivers of all motor vehicles in the UK. The regulations are updated from time to time, and are much stricter for those who wish to hold or retain a licence for a public service vehicle (PSV) or heavy goods vehicle (HGV) than for driving a car for personal use only. Patients with symptomatic heart failure are likely to be disqualified from holding a PSV or HGV licence, but may be re-licensed if they fulfil certain criteria. It is the responsibility of the patient to inform DVLA of any medical condition that may impact on their ability to drive, but the guideline development group considered it important to recommend that physicians are up to date with current guidelines. The ultimate decision regarding licensing rests with the DVLA.

RECOMMENDATION

R20.

HGV and PSV licence: Physicians should be up to date with the latest DVLA guidelines. Check the website for regular updates: www​.dvla.gov.uk [GPP]

7.2. Pharmacological treatment of heart failure due to LV systolic dysfunction

Drug therapy is required for the vast majority of patients with heart failure. This section should be read in conjunction with the guidance on the sequencing of therapy, in particular the treatment algorithm (p 54). It is the responsibility of the individual prescriber to check the dosage of medication, as well as the cautions and contra-indications. This document should be read as a guide to treatment rather than being considered a protocol that must be followed prescriptively in all patients. Treatment should be tailored to the individual patient, with referral for more specialist advice being considered where appropriate.

In general, the dose of drugs used for improving symptoms and exercise capacity can be adjusted according to patient responses, but drugs used with the aim of improving longevity or reducing hospitalisation rates should not usually be adjusted on this basis; instead attempts should be made to ensure that the patient is treated with the doses proven to be effective in RCTs (details in tables 47), or if this is not possible, the maximum tolerated dose.

Table 4. Diuretics (oral): dosages and side effects.

Table 4

Diuretics (oral): dosages and side effects.

Table 5. Practical recommendations on the use of ACE inhibitors.

Table 5

Practical recommendations on the use of ACE inhibitors.

Table 6. Practical recommendations on the use of beta-blockers.

Table 6

Practical recommendations on the use of beta-blockers.

Table 7. Practical recommendations on the use of spironolactone.

Table 7

Practical recommendations on the use of spironolactone.

Evidence statements and recommendations on specific drugs

7.2.1. Diuretics

Diuretics remain a key element in the treatment of heart failure. Diuretics preceded the advent of randomised control trials, and there are no large or long-term placebo controlled trials of their use. A systematic review of a number of small randomised trials indicated a possible benefit from diuretics in terms of mortality, compared to placebo.65

One small study66 demonstrated that patients with symptomatic heart failure deteriorated (increased body weight, reduced walking distance and worse quality of life) when diuretic therapy was withdrawn. (III)

Diuretics improve symptoms (breathlessness) and exercise performance in patients with heart failure.67 It is common practice to initiate diuretic therapy at low doses,68 and to increase the dose as required to control fluid retention – provided renal function does not deteriorate substantially. Most patients with heart failure who require diuretic therapy are treated with loop diuretics, rather than thiazides, as they are more powerful agents. Combination diuretic therapy, with a loop diuretic and a potassium sparing diuretic, may be used to increase the diuresis and also reduce the risk of hypokalaemia. The risk of hypokalaemia is less if an ACE inhibitor is used (see section on ACE Inhibitors, p 37). (Ib)

Health economic evidence: There are no economic evaluations of the use of diuretics in the treatment of heart failure. There is some evidence from the United States which suggests that the total costs of treatment with torasemide are less than those with furosemide, despite the higher acquisition cost of the newer drug (see Appendix D).

RECOMMENDATION
R21.

Diuretics should be routinely used for the relief of congestive symptoms and fluid retention in patients with heart failure, and titrated (up and down) according to need following the initiation of subsequent heart failure therapies. [C]

7.2.2. Angiotensin converting enzyme (ACE) inhibitors

Updated in August 2010

Systematic reviews of randomised controlled trials comparing ACE inhibitor to placebo have found that ACE inhibitor therapy in patients with heart failure due to left ventricular systolic dysfunction increases life expectancy69,70 compared to placebo.71 The effect is more marked in patients with more severe LV systolic impairment, or more severe symptoms – although there is benefit for all NYHA classes.70 Compared with placebo, ACE inhibitor therapy also reduces the risk of hospitalisation for heart failure in such patients, and also for patients with asymptomatic left ventricular systolic dysfunction.69,70,72 (Ia)

The symptoms of heart failure in patients with heart failure due to left ventricular systolic dysfunction improve on therapy with an ACE inhibitor.72,73 There is some evidence from a randomised controlled trial that quality of life improves with ACE inhibitor therapy in this group.74 Exercise performance has not consistently been shown to improve with ACE inhibitor therapy for all patients with heart failure due to left ventricular systolic dysfunction.71,72,74 However, a systematic review and a subsequent randomised controlled trial suggest a greater improvement in patients with more depressed LV ejection fraction.71,74 (Ia)

High doses of ACE inhibitors lower blood pressure more than lower doses but do not necessarily confer greater benefit in terms of improving symptoms or life expectancy.75,76 A higher dose does appear to reduce the risk of hospitalisation due to worsening heart failure more than lower dose.75 (Ib)

In the absence of any large RCT with mortality as an outcome, the decision was taken not to use surrogate outcomes for intra-class comparisons.

Health economic evidence: Treatment of heart failure with ACE inhibitors is cost effective, largely due to the costs saved from the reduced risk of hospitalisation. Treatment can be cost saving and has very favourable cost effectiveness ratios even when conservative assumptions are employed.

RECOMMENDATIONS
R22.

All patients with heart failure due to left ventricular systolic dysfunction should be considered for treatment with an ACE inhibitor. [A]

R23.

ACE inhibitor therapy should be instituted in patients with heart failure due to left ventricular systolic dysfunction before beta-blockade is introduced. [A]

R24.

ACE inhibitor therapy should be initiated at the appropriate dose (see Table 5), and titrated upwards at short intervals (eg every two weeks) until the optimal tolerated or target dose is achieved. [GPP]

R25.

Blood biochemistry (urea, creatinine and electrolytes) should be measured after initiation and at each dose increment. [GPP]

Absolute contraindications to the use of ACE inhibitors include a history of anuria or angioedema with past exposure to the drug, bilateral renal artery stenosis, pregnancy, and cardiogenic shock. Hypotension is not necessarily a contraindication, but consultation with a specialist is advised before use in a patient with a systolic blood pressure less than 80 mmHg. Risk factors for ACE-induced hypotension include hyponatraemia, hypovolaemia, and high dose diuretics. Therefore when ACE inhibitors are introduced in patients who are already taking a high dose of a loop diuretic (eg furosemide 80 mg), the ACE inhibitor may need to be initiated under specialist supervision. ACE inhibitor therapy may be harmful in patients with severe aortic stenosis (see section on valve disease, p 60).

As a general rule, ACE inhibitors should be used with caution in patients with a serum creatinine > 200 μmol/L or a potassium > 5.0 mmol/L. A small rise in serum creatinine is frequently observed in patients with heart failure and is not necessarily a reason for discontinuation. In patients without fluid retention, a reduction in diuretic dose may improve renal function. Risk factors for hyperkalemia during ACE inhibitor therapy include pre-existing renal dysfunction, concomitant use of potassium-sparing diuretics, and diabetes.

7.2.3. Beta-blockers

Updated in August 2010

Many large clinical trials reviewed in four meta-analyses, and one subsequent RCT have shown that several beta-blockers increase life expectancy in patients with heart failure due to LV systolic dysfunction, compared with placebo. This effect has been seen in patients with all functional classes of heart failure (NYHA classes I – IV).77–82 (Ia)

In randomised controlled trials, evaluated in three large systematic reviews of long-term outcomes, the use of certain beta-blockers in patients with heart failure significantly reduces hospitalisation compared to placebo, and has an even more marked effect on hospitalisation due to heart failure.77,79,81 (Ia)

Beta-blockers may not all have the same efficacy. The best evidence of benefit exists for bucindolol, carvedilol and modified-release metoprolol; there is little evidence of benefit from other beta-blockers.77,83,84 (Ia)

There is little evidence to suggest a clinically important difference in the effect on hospitalisation and mortality between selective and non-selective beta-blockers77 or those with or without vasodilating properties that have been examined in randomised control trials (carvedilol, metoprolol, bisoprolol).81 A direct head-to-head comparison of carvedilol with metoprolol in a large randomised trial (COMET) has completed follow-up, and the results will be reported in 2003.85 This will provide more robust evidence as to whether there is a clinically important difference in the effect of beta-blockers in patients with heart failure, and may influence future recommendations on the use of this class of drugs in the management of heart failure. (Ia)

There are no randomised clinical trials of atenolol, or some other commonly used beta-blockers, in patients with heart failure. The consensus among the guideline development group was that if a patient with heart failure due to LV systolic dysfunction not already on beta-blockade therapy then they should be commenced on a beta-blocker licensed for the treatment of heart failure in the UK at the time of issue of this guideline (bisoprolol or carvedilol). Alternatively, if a patient developed heart failure due to LV systolic dysfunction and was already on a beta-blocker for a concomitant condition such as angina or hypertension, then the physician could either decide to change the beta-blocker to one of the beta-blockers licensed for the treatment of heart failure, in the UK at the time of issue of this guideline, or continue with the agent already prescribed. (IV)

Health economic evidence: There is less economic evidence on beta-blockers than ACE inhibitors, but the evidence that does exist consistently shows beta-blockers to be cost effective, largely through the costs saved from the reduced risk of hospitalisation.

In the UK, only carvedilol and bisoprolol are licensed for the treatment of heart failure (at the time of issue of this guideline). No study has made a direct comparison between carvedilol and bisoprolol, and there is no evidence on their relative cost-effectiveness (see Appendix D).

The BNF recommends that treatment should be initiated by a doctor experienced in the management of heart failure. This may include general practitioners and other clinicians with a special interest in the condition.

Effort should be made to achieve the doses of beta-blockers that have been shown to be of benefit in terms of mortality in large clinical trials (as shown in Table 6). Although beta-blockers can cause fluid retention and fatigue, maximum doses were generally well tolerated in the randomised trials that were included in systematic reviews in this area.68,82,86–90 (Ia)

RECOMMENDATIONS
R26.

Beta-blockers licensed for use in heart failure should be initiated in patients with heart failure due to LV systolic dysfunction after diuretic and ACE inhibitor therapy (regardless of whether or not symptoms persist). [A]

R27.

Beta-blockade therapy for heart failure should be introduced in a ‘start low, go slow’ manner, with assessment of heart rate, blood pressure, and clinical status after each titration. [C]

R28.

Patients who develop heart failure due to LV systolic dysfunction and who are already on treatment with a beta-blocker for a concomitant condition (eg angina, hypertension) should continue with a beta-blocker – either their current beta-blocker or an alternative licensed for heart failure treatment. [GPP]

7.2.4. Aldosterone antagonists

Updated in August 2010

These drugs also act as potassium-sparing diuretics. Currently, the only aldosterone antagonist licensed for heart failure in the UK is spironolactone. A more selective aldosterone antagonist, eplerenone, has been developed and a large mortality trial in patients with heart failure after myocardial infarction (EPHESUS) is due to be published in 2003.91 The results of this trial may influence future recommendations on the use of aldosterone antagonists in patients with heart failure.

Spironolactone

In patients with moderate to severe heart failure (NYHA Class III and IV) due to LV systolic dysfunction, the addition of low-dose spironolactone to therapy with a loop diuretic and ACE inhibitor (±digoxin) has been shown in a large randomised controlled trial to increase life expectancy when compared to placebo.92 In addition, hospitalisation for cardiac causes is greatly reduced.92 (Ib)

Use of this drug may increase blood potassium93 but there was no significant clinical problem with hyperkalaemia in the patients included in the RALES trial, which involved close monitoring and titration.92 In this trial, patients with raised serum creatinine or potassium concentration were excluded. (Ib)

Health economic evidence: No relevant economic evidence relating to spironolactone has been identified.

Eplerenone

Eplerenone is an aldosterone antagonist with fewer side-effects than spironolactone. There is no RCT evidence relating to patients with heart failure currently available to support the use of eplerenone in such patients. The evidence for the clinical effect of eplerenone in patients with heart failure will become clearer when the EPHESUS trial reports.94 This drug is not currently licensed for use in the UK. (IIb)

RECOMMENDATIONS
R29.

Patients with heart failure due to LV systolic dysfunction who remain moderately to severely symptomatic despite optimal therapy (as outlined in the algorithm) should be prescribed spironolactone at a dose of 12.5 to 50 mg once per day – specialist advice should be sought. [A]

R30.

Patients with heart failure taking spironolactone should have blood potassium and creatinine levels monitored for signs of hyperkalaemia and/or deteriorating renal function (see Table 7 for further details). If hyperkalaemia is a problem then the dose of spironolactone should be halved and biochemistry rechecked. [GPP]

7.2.5. Digoxin

Despite a small systematic review that suggests that fewer patients withdraw from randomised trials of therapy when on digoxin than on placebo,308 there are no published data from randomised control trials on the effect of digoxin on the signs and symptoms (except for exercise performance)95,96 and quality of life96 of patients with heart failure. Digoxin reduces the risk of admission to hospital with worsening heart failure in patients with heart failure due to LV systolic dysfunction in sinus rhythm, and may reduce heart failure-specific mortality.97 However, a large systematic review and two additional RCTs with medium-term follow up, suggest that it does not increase overall life expectancy.95,97 (Ib)

There is some evidence from a medium sized RCT that digoxin therapy may prevent deterioration in maximal exercise performance for patients with heart failure due to LV systolic dysfunction and in sinus rhythm95 – and withdrawal may lead to deterioration in maximal, but not sub-maximal, exercise performance.96 The clinical effects of the withdrawal of digoxin may be more marked in patients with poorer LV systolic function (eg lower ejection fractions) and more severe symptoms (eg worse NYHA class).96 (Ib)

Digoxin has a narrow therapeutic window, with arrhythmias and gastrointestinal side effects being the most common clinical problems. In clinical trials digoxin therapy rarely has to be withdrawn for toxicity reasons.95,97 (Ib)

The use of digoxin has an important role in patients with heart failure and atrial fibrillation. Initial treatment with digoxin need not preclude the subsequent use of a beta-blocker.98 (IV)

Health economic evidence: There are no economic evaluations of the use of digoxin to treat heart failure in the UK. There is one cost-effectiveness analysis from the United States (based on international RCT evidence) that shows that digoxin may be cost saving in the treatment of patients with heart failure, whether or not they are also receiving ACE Inhibitors (see Appendix D).99

The usual daily dose of oral digoxin is 125 to 250 μg if the serum creatinine is within the normal range. Higher doses (> 250 μg) are rarely used for heart failure treatment. Lower doses are used if the patient is elderly (over age 70 years) or has impaired renal function. There is little relationship between digoxin concentration and therapeutic effects.68

A number of drugs can alter the pharmacokinetics of digoxin. Those producing the most significant perturbation of digoxin levels are:

  • anti-arrhythmic drugs affecting renal clearance and/or volume of distribution (verapamil, amiodarone, propafenone and quinidine)
  • drugs increasing its absorption (erythromycin, omeprazole and tetracycline)
  • drugs decreasing its absorption (colestipol, cholestyramine).

A number of drugs can alter the pharmacokinetics of digoxin. See the BNF (http://bnf.org) for a comprehensive list.

The role of therapeutic monitoring of serum digoxin concentrations is discussed in the section on monitoring (section 8).

RECOMMENDATIONS

Updated in August 2010

R31.

Digoxin is recommended for:

  • worsening or severe heart failure due to LV systolic dysfunction despite ACE inhibitor, beta-blocker and diuretic therapy [A]
  • patients with atrial fibrillation and any degree of heart failure. [C]

7.2.6. Angiotensin-II receptor antagonists

Updated in August 2010

Currently, none of the angiotensin-II receptor antagonists is licensed for use in heart failure in the UK. The clinical evidence for the use of this class of drugs in heart failure is still emerging with several large randomised trials ongoing.

Angiotensin-II receptor antagonists have not been shown to increase life expectancy compared to ACE inhibitor therapy for patients with heart failure due to left ventricular systolic dysfunction in several RCTs.100–103 (Ia)

One systematic review of 17 randomised controlled trials demonstrated that the combination of angiotensin-II receptor antagonists and ACEI did not reduce risk of mortality as compared to ACEI on their own. However, significantly fewer patients required hospitalisation with the dual therapy.100 (1a)

One large prospective randomised trial, Val-HeFT, showed that the addition of the angiotensin-II receptor antagonist valsartan, at doses of 40 mg to 160 mg twice daily, to standard therapy with a diuretic and ACE inhibitor (with or without digoxin), does not improve life expectancy for patients with heart failure due to left ventricular systolic dysfunction, but reduces hospitalisation with worsening heart failure.103 (Ib)

Clarification will emerge from ongoing clinical trials as to the possible harm from the ‘triple combination’ of ACE inhibitor, angiotensin-II receptor antagonist and beta-blocker, suggested by post hoc subgroup analysis. In the meantime this combination should be avoided.

Therapy with an angiotensin-II receptor antagonist in patients with heart failure due to LV systolic dysfunction who are not on an ACE inhibitor or cannot tolerate an ACE inhibitor (for example, due to a cough) reduces mortality compared with treatment with placebo, as indicated by a systematic review.102 There are few data on the impact of angiotensin-II receptor antagonists on symptoms, quality of life and exercise performance in patients with heart failure due to LV systolic dysfunction.101,103,104 (Ia)

In clinical trials, angiotensin-II receptor antagonists are better tolerated than ACE inhibitors.101,104 Hypotension and reversible renal dysfunction are the most common serious side effects. (Ib)

A large clinical trial examining the effect of candesartan as an addition to ACE inhibition in patients with heart failure due to LV systolic dysfunction, as an alternative to ACE inhibition in patients intolerant of such therapy, and in patients with diastolic heart failure is due to report in 2003 (CHARM).105 A large randomised outcome trial examining the effects of valsartan monotherapy or as an addition to ACE inhibition in post myocardial infarction patients who have either clinical or radiological signs of heart failure and/or evidence of left ventricular systolic dysfunction is due to report in 2003 (VALIANT). The results of these studies may influence future recommendations on the use of this class of drugs in the management of heart failure.

Health economic evidence: There are no economic evaluations of the use of angiotensin-II receptor antagonists in the treatment of heart failure in the UK. There is one cost effectiveness analysis from the United States, based on international RCT evidence, comparing losartan with the ACE inhibitor, captopril. This shows little difference between the cost effectiveness ratios of these two drugs when used for symptomatic heart failure in older people (see Appendix D).106

RECOMMENDATIONS
R32.

At the time of issue of this guideline, angiotensin-II receptor antagonists (see Table 8) are not licensed in the UK for heart failure and studies are ongoing. However, angiotensin-II receptor antagonists may provide an alternative to ACE inhibitors for patients intolerant of ACE inhibitors (for example, because of cough). [A]

R33.

The triple combination of ACE inhibitor, beta-blocker and angiotensin-II receptor antagonist should be avoided, pending the results of further trials. [GPP]

Table 8. Currently available angiotensin-II receptor antagonists.

Table 8

Currently available angiotensin-II receptor antagonists.

7.2.7. Amiodarone

A small number of RCT and meta-analyses have demonstrated that amiodarone is effective against most ventricular arrhythmias.107–109 Evidence from one-meta analysis with long-term outcome assessment suggests a neutral effect on mortality in patients with heart failure.107,110,111 (Ia)

Amiodarone has numerous side effects. Photosensitivity and asymptomatic corneal micro-deposits are common but other side effects are potentially more serious, eg thyroid dysfunction, pulmonary fibrosis, liver damage, neuropathy.107–110 (Ia)

Because of the potentially serious side effects from long-term therapy with amiodarone, the guideline development group recommended that the decision to initiate, and to continue, such therapy should be made in consultation with a specialist.

Health economic evidence: No relevant economic evidence relating to amiodarone was identified.

RECOMMENDATIONS
R34.

The decision to prescribe amiodarone should be made in consultation with a specialist. [GPP]

R35.

The need to continue the prescription should be reviewed regularly. [GPP]

R36.

Patients taking amiodarone should have a routine six-monthly clinical review, including liver and thyroid function test, and including a review of side effects. [GPP]

7.2.8. Anticoagulants

Randomised control trials have demonstrated that warfarin reduces the risk of stroke in patients with heart failure with atrial fibrillation. Patients with heart failure were included within these studies.112 (Ia)

There is no RCT evidence that patients with heart failure and intracardiac thrombus, left ventricular aneurysm, and/or a history of thromboembolism (in the absence of atrial fibrillation) benefit from oral anticoagulation. The consensus among the guideline development group was that warfarin is likely to be beneficial in such circumstances. (IV)

One RCT reported no difference in the risk of death, myocardial infarction and/or stroke for patients with heart failure in sinus rhythm when taking warfarin as opposed to aspirin or no anticoagulant/anti-platelet therapy.113 There is an ongoing trial (WATCH), which will add to the evidence in this area. (Ib)

RECOMMENDATIONS
R37.

Anticoagulation is indicated for patients with the combination of heart failure and atrial fibrillation (see also atrial fibrillation section, p 60). [A]

R38.

In patients with heart failure in sinus rhythm, anticoagulation should be considered for those with a history of thromboembolism, left ventricular aneurysm, or intracardiac thrombus. [GPP]

For guidance on international normalised ratio (INR) levels in atrial fibrillation, please refer to the Haemostasis and Thrombosis Task Force Guidelines on Oral Anticoagulation114 at www.bcshguidelines.com/pdf/bjh715.pdf

7.2.9. Aspirin

There is systematic review evidence that aspirin reduces the risk of vascular events in patients with atherosclerotic arterial disease.115 Aspirin is currently recommended for patients with coronary heart disease,116 although specific RCT evidence for its benefit in patients with heart failure is lacking. (Ia)

Concern has been raised from post hoc analyses of RCTs that aspirin may reduce the beneficial effect of ACE inhibitors in patients with heart failure or atherosclerotic arterial disease,117,118 although not all reports confirm this.119,120 In order to provide more robust evidence prospective RCTs to examine this concern are planned. (IIb)

The guideline development group discussed the concerns regarding aspirin use in patients with heart failure, many of whom are also prescribed an ACE inhibitor. In the absence of conclusive evidence, and general consensus as to the benefits of aspirin in patients with atherosclerotic arterial disease, the decision was made to continue to support the use of aspirin in patients with heart failure who also had atherosclerotic arterial disease.

RECOMMENDATION
R39.

Aspirin (75–150 mg once daily) should be prescribed for patients with the combination of heart failure and atherosclerotic arterial disease (including coronary heart disease). [B]

7.2.10. Statins (hydroxymethylglutaryl-coenzyme A reductase inhibitors)

Updated in August 2010

In the UK, coronary artery disease (CAD) is the single most common cause of heart failure. Patients with heart failure that subsequently develop myocardial infarction and/or unstable angina have a worse outcome than patients without ischaemic events.121,122 (Ib)

Several large RCTs report that statins reduce the frequency of ischaemic events and prolong life expectancy in patients with known CAD.122–125 The risk of developing heart failure is also reduced.126 Although post hoc analysis suggests that statins are effective in patients with and without heart failure,122 many statin trials have excluded patients with severe heart failure. (Ib)

Experimental studies suggest that statins may improve left ventricular function through a variety of mechanisms not linked to the prevention of myocardial ischaemia, but may also increase the oxidative stress and the effects of endotoxin in patients with heart failure.127 The effect of statins on ventricular function and heart failure progression has not been specifically addressed in a randomised controlled trial.

Health economic evidence: There is evidence that statins are a cost effective therapy in patients with cardiovascular disease who are at high risk of CHD events.128 However, there is no specific cost-effectiveness information available on the use of statins in patients with heart failure.

RECOMMENDATION
R40.

Patients with the combination of heart failure and known atherosclerotic vascular disease should receive statins only in accordance with current indications. Specific trials in this area are ongoing. [GPP]

7.2.11. Isosorbide/hydralazine combination (specialist initiation only)

Updated in August 2010

Oral isosorbide dinitrate in combination with hydralazine has been shown in one large RCT (which included only men) with long term outcomes to extend life expectancy in patients with heart failure compared with placebo.129 It is not, however, as effective as ACE inhibitors.130–135 (Ia)

Such combination therapy is less well tolerated than ACE inhibitors, with more frequent adverse events than placebo, including gastrointestinal problems and headaches.130,132,133,136,137 (Ib)

There is evidence that oral isosorbide dinitrate in combination with hydralazine improves exercise capacity and in the one trial that reported on this outcome increases LV ejection fraction.129,130 The benefit of hydralazine and dinitrates (in combination) as an additive therapy to ACE inhibitors or beta-blockers remains unclear. (Ib)

Health economic evidence: One study in the US considered the cost effectiveness of isosorbide/hydralazine combination in comparison to standard therapy with digoxin and diuretics, using data from the V-HeFT II trial. This was found to be a cost effective therapy in the US context, but the generalisability of this result to the UK is questionable.

RECOMMENDATION
R41.

An isosorbide/hydralazine combination may be used in patients with heart failure who are intolerant of ACE inhibitors or angiotensin-II receptor antagonists. [A]

7.2.12. Inotropic agents (specialist use only)

Inotropic agents are of proven clinical benefit in the short-term treatment of acute decompensation. One large and two small RCTs suggest that dobutamine, milrinone and enoximone improve symptoms and exercise performance.138–140 However, a large multi-centre randomised controlled trial found no effect of short term inotropic therapy on hospitalisaton of patients with acute decompensation of heart failure.140 (Ib)

Intravenous inotropic agents increase mortality when used as chronic therapy and no oral inotropic agent has been shown to be of benefit in chronic therapy in terms of increasing life expectancy, although they can improve symptoms.139,141–144 (Ia)

Randomised control trials of the chronic use of inotropic agents at different dose levels (and of novel inotropic agents) in patients with heart failure are ongoing.

Health economic evidence: No relevant economic evidence relating to inotropic agents was identified.

RECOMMENDATION
R42.

Intravenous inotropic agents (such as dobutamine, milrinone or enoximone) should only be considered for the short-term treatment of acute decompensation of chronic heart failure. This will require specialist advice. [A]

7.2.13. Calcium channel blockers

Three RCTs with medium- to long-term follow up suggest that calcium channel blockers do not improve life expectancy compared with placebo in patients with heart failure who are already receiving an ACE inhibitor.145–147 Verapamil, diltiazem and short-acting dihydropyridines such as nifedipine can cause clinical deterioration.146,148 (Ia)

Amlodipine, a long-acting dihydropyridine, is not harmful in terms of adverse events.147,149 (Ib)

Health economic evidence: No relevant economic evidence relating to calcium channel blockers was identified.

RECOMMENDATION
R43.

Amlodipine should be considered for the treatment of co-morbid hypertension and/or angina in patients with heart failure, but verapamil, diltiazem or short acting dihydropyridine agents should be avoided. [A]

7.2.14. Others

Nesiritide

Nesiritide is synthetic human BNP. Three medium-term RCTs in patients with heart failure suggest it has short-term haemodynamic benefits in patients with acute decompensation. It is currently not licensed for use in the UK.150–152

Levosimendan

Levosimendan is a calcium sensitiser. Three medium-sized RCTs of patients with heart failure with severely depressed LV ejection fraction suggest this drug may provide short-term haemodynamic benefits in patients with acute decompensation. It is currently not licensed for use in the UK.153–155

Other pharmacological therapies

The guideline development group reviewed both systematic review and small scale RCT evidence for several other drug therapies. The drugs considered were: d-sotalol,156 epoproserol,157,158 magnesium supplementation, vitamin E supplementation,159 interferon/thymomodulin,146 human recominant growth hormone,160 L-cartinine,161 pentoxifylline,162 immunosuppressants.163

The group concluded however, that the evidence in non-specialist practice was not robust enough to warrant inclusion in the guideline.

7.2.15. Major co-morbidities that impact on the pharmacological management of heart failure

Updated in August 2010

The presence of certain co-morbidities may affect the drugs that can be used for the treatment of heart failure, or increase the likelihood of side effects. These are summarised in Table 9.

Table 9. Major co-morbidities that impact on the management of heart failure.

Table 9

Major co-morbidities that impact on the management of heart failure.

7.2.16. Drugs to be avoided or used with caution in heart failure

Patients with heart failure may have significant renal (and hepatic) impairment. Drugs cleared predominantly by the kidney (and liver) can accumulate in these patients causing drug-related toxicity – these include drugs used to treat heart failure itself, such as ACE inhibitors and digoxin.

Non-prescription drugs (such as herbal remedies) can have important interactions with the prescription drugs taken by patients with heart failure, eg St John’s wort can affect the blood levels of both warfarin and digoxin. Please see the section on anxiety and depression for further details (section 11). Comprehensive details on non-prescription drugs can be found on http://herbmed.org

Non steroidal anti inflammatory drugs (NSAIDs) may exacerbate oedema and renal impairment in patients with HF and should be used with caution – this applies to both non-selective agents as well as the newer COX-2 selective agents. Oral and intravenous steroids may also exacerbate oedema. Drugs with a negative inotropic effect should also be avoided – such as verapamil, diltiazem, and Class I anti-arrhythmic drugs.

This guideline can only provide an outline of the relevant issues. Please see the British National Formulary for more complete listings and detail (http://bnf.org).

7.2.17. Side effects of drugs commonly used in the treatment of heart failure

All drugs have side effects. The major complications of drugs commonly used for the treatment of heart failure are listed in Table 10. Further details can be found in the ABPI Electronic Medicines Compendium, which can be found at www.emc.vhn.net

Table 10. Major complications of drug therapy in chronic heart failure.

Table 10

Major complications of drug therapy in chronic heart failure.

It is important that possible side effects are discussed with patients (and carers where appropriate).

7.2.18. Improving adherence to pharmacological therapy

There is evidence to suggest that non-adherence with treatment is a significant cause of readmission in patients with heart failure.166,167 There are many causes of non-adherence, which may be accidental or deliberate. There are few studies specific to patients with heart failure but the guideline development group considered that it was reasonable to extrapolate from studies in other chronic conditions.

Simplifying dosing regimens, and educating patients and their carers about their medicines, appear to be important. Three systematic reviews168–170 including mixed populations of patients with chronic conditions requiring chronic medication, reported that a simplified dosing regime (reductions in number of medications and frequency of dosing from three times daily to once daily where possible) improved adherence with the number of doses correctly taken. There is, however, mixed evidence for the benefit of reducing twice-daily regimes to once daily. There is no evidence that changing the timing of doses improves adherence. None of these studies demonstrated direct benefits in terms of patient outcome. (Ia)

RECOMMENDATION
R44.

Dosing regimens should be kept as simple as possible, and the healthcare professional should ensure that the patient and carer are fully informed about their medication. [B]

7.3. Algorithm for the pharmacological treatment of symptomatic heart failure due to LV systolic dysfunction

Updated in August 2010

Patients with symptomatic heart failure due to LV systolic dysfunction should be treated with the following drugs (if tolerated and not contraindicated) and in the sequence indicated. The reader must refer to the text of the main guideline for more detailed discussion and explanation.

Please note:

  • Diuretic is first line therapy when a patient presents with acute pulmonary oedema
  • Please refer to tables 37 (in Section 7) for starting doses of drugs
  • The arrow on the left indicates the increasing likelihood of the need for specialist input.
Table 3. Drugs in this guideline unlicensed for the treatment of heart failure or its common signs and symptoms in the UK at the time of issue of this guideline.

Table 3

Drugs in this guideline unlicensed for the treatment of heart failure or its common signs and symptoms in the UK at the time of issue of this guideline.

Flowchart Icon

Flowchart (PDF, 100K)

7.4. Invasive procedures

Although drug therapy is the mainstay of treatment of heart failure, some patients will also benefit from diagnostic or interventional invasive procedures. These procedures are normally organised by a specialist. Several RCTs are currently examining the benefit of such procedures, and the evidence base is likely to change substantially in the next 5–10 years. This guideline can only give general advice, and specialist advice is strongly recommended where such procedures might be considered.

7.4.1. Coronary revascularisation

Although ischaemic heart disease is the commonest cause of heart failure due to left ventricular damage in the UK, the benefits of revascularisation in patients with congestive heart failure remain uncertain, with evidence limited to a systematic review of cohort studies of patients with moderate to severe LV systolic dysfunction.179 Subgroup analyses in large randomised trials of surgical and medical therapy in patients with chronic stable angina180 have suggested that patients with a low ejection fraction and triple vessel coronary artery disease may have improved survival with surgery. However, left ventricular dysfunction and severe symptoms increase the risks of coronary artery bypass grafting (CABG). Although a number of small studies have suggested that revascularisation may be beneficial in patients with heart failure with large areas of noncontractile but ‘viable’ myocardium, there is an absence of randomised studies of surgery in patients with heart failure. Further data will become available in the near future. This will provide a clearer picture of which patients are likely to benefit from coronary revascularisation. (III)

There are a variety of imaging techniques to detect non-contractile but viable myocardium including nuclear imaging, stress echocardiography and magnetic resonance imaging.

Health economic evidence: Little is known about the health economics of revascularisation in heart failure. A health technology appraisal of interventions for chronic stable angina in 1998 identified no relevant economic evaluations of CABG or PTCA.181

RECOMMENDATION

R45.

Coronary revascularisation should not be routinely considered in patients with heart failure due to systolic left ventricular impairment, unless they have refractory angina. [C]

7.4.2. Cardiac transplantation

Although there are no randomised studies of transplantation in patients with heart failure owing to the intrinsic practical limitations in this field, observational data demonstrate an improved quality of life after transplantation with a 70–80% survival at five years.182 The major limitations of cardiac transplantation are limited donor organ availability and the fact that most patients do not fulfil current selection criteria (see Table 11). Long-term prognosis is limited by the side effects of immunosuppression (hypertension, malignancy, renal failure and infection) and the development of graft vascular disease. (IV)

Table 11. Indications for heart transplantation, adapted from ACC/AHA & ESC Guidelines.

Table 11

Indications for heart transplantation, adapted from ACC/AHA & ESC Guidelines.

Health economic evidence: There are no recent economic evaluations of cardiac transplantation in the UK. While this is a relatively expensive procedure the benefits in terms of both quality and length of life have been shown to be large, resulting in favourable cost effectiveness ratios (see Appendix E).

RECOMMENDATION

R46.

Specialist referral for transplantation should be considered in patients with severe refractory symptoms or refractory cardiogenic shock. [C]

7.4.3. Ventricular assist devices (VADs)

The worldwide experience of using implantable ventricular assist devices is steadily increasing, with a small number of patients continuing with such mechanical support for more than one year in one prospective trial and in case series.183,184 Although some patients appear to recover during VAD therapy, there are insufficient data on the mechanisms of response and the identification of patients in whom devices can be safely removed to justify recommendation of more widespread use of VADs as a bridge to recovery185,186 or as chronic therapy. (Ib)

Health economic evidence: These are a relatively new and rapidly evolving technology. At present the cost of the devices is high and the evidence on potential benefits is not of sufficient quality to conduct an economic evaluation. A study of the clinical and cost effectiveness of VADs has recently been funded by the health technology assessment programme and is due to report in 2004 (see Appendix E).

7.4.4. Cardiac resynchronisation therapy

Updated in August 2010

Approximately 30% of patients with heart failure have delayed or incoordinate electrical activation of ventricular contraction. This is manifest on a surface ECG by a bundle branch block pattern and a QRS duration > 120 ms.187 The presence of left bundle branch block is associated with adverse haemodynamic consequences and reduced survival in patients with heart failure. Two small, short-term RCTs have shown that cardiac function or oxygen uptake can be improved in patients with LBBB by simultaneously pacing the left and right ventricles (referred to as cardiac ‘resynchronisation’).188,189 (Ib)

Randomised trials (often employing a cross-over design) of biventricular pacing have demonstrated improvements in symptoms, exercise tolerance and reduced hospitalisations for heart failure. The effect on long-term survival is currently being evaluated in ongoing studies189–191 with publication of results expected imminently. (Ib)

Health economic evidence: Implantation and follow-up costs of CRT devices are not significantly dissimilar to those seen with standard dual chamber pacemakers; preliminary results from trials suggest potential cost savings through lower hospitalisation rates coupled with overall benefits in terms of mortality and morbidity.

The results of a large clinical trial examining the impact of cardiac resynchronisation therapy (with or without an implantable cardiac defibrillator) in patients with NYHA Class III or IV heart failure, a QRS duration > 120 mseconds and left ventricular ejection fraction (LVEF) <= 35% is due to be published in 2003. This study (COMPANION-CHF)192 is likely to influence future recommendations on the use of cardiac resynchronisation therapy (with or without an implantable cardiac defibrillator) in patients with heart failure.

RECOMMENDATION

R47.

Resynchronisation therapy should be considered in selected patients with left ventricular systolic dysfunction (LVEF <= 35%), drug refractory symptoms, and a QRS duration > 120 ms. The result of ongoing trials will help guide appropriate patient selection. [A]

7.4.5. Implantable cardioverter-defibrillators (ICDs)

Updated in August 2010

In a large systematic review of CHD patients, ICDs have been shown to prolong life in patients with impaired left ventricular function and a history of sustained ventricular arrhythmia.193 There are no large-scale randomised data in unselected patients with heart failure. Ongoing RCTs will help clarify this area.

A NICE health technology appraisal provided guidance on the use of ICDs for arrhythmias,194 and the recommendations are summarised below.

Health economic evidence: A review of the clinical and cost effectiveness of ICDs for the HTA programme revealed a very wide range of cost effectiveness ratios. The applicability of this evidence to the treatment of heart failure is unclear. As this technology is rapidly evolving the currently high cost of devices is likely to fall and ongoing trials are likely to provide better evidence on potential benefits. The HTA is due to be updated in September 2003.

RECOMMENDATION

R48.

Recommendation from NICE Technology Appraisal Guidance No. 11 Guidance on the use of implantable cardioverter defibrillators for arrhythmias (www​.nice.org.uk/Docref.asp?d=10239): [NICE]

The use of implantable cardioverter defibrillators (ICDs) should be routinely considered for patients in the following categories:

“Secondary prevention” ie for patients who present, in the absence of a treatable cause, with:

  • Cardiac arrest due to either ventricular tachycardia (VT) or ventricular fibrillation (VF).
  • Spontaneous sustained VT causing syncope or significant haemodynamic compromise.
  • Sustained VT without syncope/cardiac arrest, and who have an associated reduction in ejection fraction (less than 35%) but are no worse than class 3 of the New York Heart Association functional classification of heart failure.

“Primary prevention” for patients (see paragraph 2.5 for definition) with:

  • a history of previous myocardial infarction (MI) and all of the following:
    1. non sustained VT on Holter (24 hour ECG) monitoring;
    2. inducible VT on electrophysiological testing;
    3. left ventricular dysfunction with an ejection fraction (EF) less than 35% and no worse than class III of the New York Heart Association functional classification of heart failure.
  • A familial cardiac condition with a high risk of sudden death, including long QT syndrome, hypertrophic cardiomyopathy, Brugada syndrome, arrhythmogenic right ventricular dysplasia (ARVD) and following repair of Tetralogy of Fallot.

7.4.6. Other invasive therapies

Patients with severe ventricular dilatation often have clinically important mitral regurgitation. Surgical correction of the mitral regurgitation has been suggested as a therapeutic option in such patients from case series but there are no controlled studies.195

Cardiomyoplasty is possibly of benefit in patients with class III heart failure, however it is currently an experimental procedure, with no RCT evidence to substantiate its use.196

Health economic evidence: There are no economic evaluations of the use of mitral valve surgery or cardiomyoplasty in the treatment of heart failure.

7.5. Oxygen therapy and continuous positive airways pressure treatment

Patients with heart failure may develop arterial hypoxaemia through mismatches in lung ventilation and perfusion, and disturbances in nocturnal ventilation and respiratory drive (including periodic breathing such as Cheyne-Stokes respiration).197,198 This may have acute and chronic deleterious effects on cardiac function.

Domiciliary oxygen therapy

One very small RCT of domiciliary oxygen for seven nights in patients with heart failure and Cheyne-Stokes respiration suggested some improvement in breathing pattern at night, but no improvement in awakenings or daytime sleepiness and functional status.199 There was a high drop out rate even during the short duration of this study. A working party report of the Royal College of Physicians included recommendations for patients with heart failure.200 Long-term oxygen therapy was recommended if there is daytime hypoxaemia (PaO2 on air of < 7.3 kPa) or nocturnal hypoxaemia with SaO2 below 90% for at least 30% of the night. There is a need for further studies in this area. (IV)

Continuous positive airways pressure (CPAP) treatment

Currently the majority of published reports relate to the use of CPAP as therapy for patients with heart failure with Cheyne-Stokes respiration. All the trials are small and may not have a sufficiently long washout period after crossover. Benefit is reported in patients with moderate to severe heart failure in terms of sleep quality,199 peak oxygen consumption during exercise,199 maximal inspiratory pressure,201 LV ejection fraction,201 and cognitive function.199 No significant differences in arterial oxygen saturations have been reported.202 The findings are mixed in terms of effect on functional status and symptoms.201,202 One of the largest RCTs to date included 66 patients with 31 randomised to CPAP at 12.5cm H2O for at least six hours at night for three months,203 with unsupervised use thereafter. Patients were stratified by whether they had Cheyne Stokes respiration or not, and for those who had there was a significant increase in LV ejection fraction. There was no significant difference in transplant-free survival to two years, but the study was underpowered to detect this. No adverse effects of CPAP were noted, which was well tolerated. There is a need for further studies in this area. (Ib)

The guideline development group was unable to come to any recommendation on the use of domiciliary oxygen or CPAP therapy for patients with heart failure. Further research is required.

7.6. Treatment of heart failure not due to LV systolic dysfunction

7.6.1. Valve disease

Clinical examination and an echocardiogram should detect valve disease. Detection is important because heart failure due to valve disease is potentially curable, but will require management that differs from that of other causes of heart failure such as LV systolic dysfunction.16,68 ACE inhibitor therapy may be harmful in patients with severe aortic stenosis. (III)

RECOMMENDATIONS

R49.

Patients with heart failure due to valve disease should be referred for specialist assessment and advice regarding follow-up. [C]

R50.

ACE inhibitor therapy should not be initiated in a patient with a clinical suspicion of haemodynamically significant valve disease, until the valve disease has been assessed by a specialist. [C]

Patients with valve disease (but no heart failure) should also be assessed by a specialist, as the onset of heart failure increases the risk of surgery and reduces the likelihood of full recovery.

7.6.2. Diastolic dysfunction

The RCT evidence for the treatment of diastolic dysfunction is sparse, but will strengthen in the next few years as the results of ongoing trials become available. The guideline development group agreed the following principles.

RECOMMENDATION

R51.

The diagnosis and treatment of diastolic dysfunction should be made by a specialist, and other conditions that present in a similar way may need to be considered. Patients in whom this diagnosis has been made should usually be treated with a low to medium dose of loop diuretics (eg < 80 mg furosemide per day). Patients who do not respond to this treatment will require further specialist advice. [GPP]

7.6.3. Other causes

The GDG agreed that the management of other causes of heart failure would require specialist input. Such causes include congenital heart disease, cardiomyopathies, and specific heart muscle disease such as amyloid.

7.6.4. Atrial fibrillation (AF)

Updated in August 2010

Atrial fibrillation is common in heart failure and may exacerbate or precipitate heart failure. Management may be directed at either controlling the heart rate or restoring and maintaining sinus rhythm which can improve symptoms, and hence quality of life.

Although there is no randomised trial evidence that restoration of normal sinus rhythm is of clinical benefit to patients with heart failure, it may be appropriate for individual patients. (III)

Amiodarone has been shown in a large scale systematic review of 32 trials to increase the chance of restoring and maintaining sinus rhythm171 although benefits on survival are unproven. (Ia)

Nodal ablation and pacemaker implantation may be of benefit in patients with intractable symptoms and poor heart rate control despite pharmacological intervention171 although more evidence in this field is required. (Ia)

A systematic review of the large RCTs of beta-blockers in patients with heart failure showed that the benefits of beta-blockers are no different in patients with atrial fibrillation than in those without.171 (Ia)

Anticoagulation in patients with heart failure and atrial fibrillation has been discussed in section 7.2.8, p 47. Readers should also see the digoxin section (7.2.5) on p 44.

RECOMMENDATIONS

R52.

For patients with heart failure and atrial fibrillation, specialist advice should be sought as to whether the aim is improvement of heart rate control or cardioversion (return to sinus rhythm). [C]

R53.

Anticoagulation is indicated for patients with heart failure and atrial fibrillation (see also anticoagulation section, p 47). [A]

Subgroups of patients with heart failure

7.6.5. Age

The average age of a patient with a new diagnosis of heart failure in the UK is 76 years.1 In principle, the pharmacological treatment for elderly patients should be similar to that of any other patient with heart failure, but tolerance may be lower, side effects more frequent, and adherence poorer.

One systematic review and five small prospective randomised trials were identified that related to the treatment of older patients, although the definitions of age cut-offs varied between studies. ACE inhibitors have been reported in one systematic review to produce more side effects but improve quality of life in older patients.172 RCT data have suggested that angiotensin-II receptor antagonists may be initiated in a similar manner in older patients as in other patients with heart failure.173 (Ia)

There is no evidence that the dose of beta-blockers should be reduced in older patients, and with low dose initiation and slow titration, trials have indicated benefit.174 (Ib)

A randomised controlled trial has reported no difference in the clinical response to digoxin compared to placebo in older patients compared with younger patients.175 More adverse events have been noted in older patients, and low dose initiation of drug therapy is particularly advised where patients have a raised blood creatinine concentration. (Ia)

RECOMMENDATIONS
R54.

The management of heart failure should be determined by clinical criteria, irrespective of the age of the patient. [A]

R55.

Tolerance of drugs may be lower and side-effects require closer and more frequent monitoring in older patients. [GPP]

7.6.6. Gender

Women tend to be under-represented in RCTs of pharmacological therapy in heart failure. The evidence that is available from post hoc analysis of randomised trials of most therapy does not suggest that the clinical effects of drugs are different. A post hoc analysis of the DIG trial suggested possible differences in mortality between men and women on digoxin.176 (IIa)

If a woman of reproductive age has heart failure, there are several important clinical considerations regarding the risk of pregnancy (to mother and child) and the possible teratogenic effects of drugs used to treat heart failure. If the woman has (or has had) peripartum cardiomyopathy (heart muscle disease of no obvious cause developing during or shortly after pregnancy) the risk of further cardiac problems in a subsequent pregnancy is substantial.177 Drugs such as ACE inhibitors and amiodarone have teratogenic effects. (III)

RECOMMENDATIONS
R56.

The principles of pharmacological management of heart failure should be the same for men and women. [GPP]

R57.

The potential teratogenic effects of drugs should be considered. [GPP]

R58.

Pregnancy in women of reproductive age who have heart failure, contraception and pregnancy should be discussed. If pregnancy is being considered or occurs, specialist advice should be sought. Subsequently, specialist care should be shared between the cardiologist and obstetrician. [GPP]

7.6.7. Ethnicity

Updated in August 2010

Non-Caucasian populations are under represented in RCTs, making it difficult to draw firm conclusions. As most evidence available is from post hoc analysis of large randomised trials more research in this area is required.178

RECOMMENDATION
R59.

The principles of pharmacological management should be the same for all patients with heart failure, regardless of ethnicity. [GPP]

Copyright © 2003, Royal College of Physicians of London.
Cover of Chronic Heart Failure
Chronic Heart Failure: National Clinical Guideline for Diagnosis and Management in Primary and Secondary Care.
NICE Clinical Guidelines, No. 5.
National Collaborating Centre for Chronic Conditions (UK).

NICE (National Institute for Health and Care Excellence)

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