Diuretics

• The recommendation to give diuretics to relieve symptoms of heart failure is consistent with guidelines from the National Institute for Health and Clinical Excellence (NICE) [National Clinical Guideline Centre for Acute and Chronic Conditions, 2010], the Scottish Intercollegiate Guidelines Network (SIGN) [SIGN, 2007], and the European Society of Cardiology (ESC) [European Society of Cardiology, 2008].
• The use of diuretics to improve congestive symptoms of heart failure is well established. Although there is no direct evidence from randomized controlled trials (RCTs), it is widely accepted that diuretics are effective at improving symptoms and exercise performance in people with heart failure.
• Limited evidence from several small RCTs indicates that diuretics may also reduce the risk of death and worsening heart failure compared with placebo.

Angiotensin-converting enzyme (ACE) inhibitors

• The recommendation to give an ACE inhibitor to all people with heart failure and left ventricular systolic dysfunction is consistent with guidelines from NICE [National Clinical Guideline Centre for Acute and Chronic Conditions, 2010], SIGN [SIGN, 2007], and ESC [European Society of Cardiology, 2008].
• Good evidence indicates that ACE inhibitors reduce the mortality and morbidity associated with heart failure.
• A systematic review of large RCTs found that ACE inhibitors reduce the risk of death from any cause, readmission because of heart failure, and re-infarction after myocardial infarction. The benefits of ACE inhibitors occur soon after the start of treatment and persist in the long term. The benefits seem to be independent of age, sex, and baseline use of diuretics, aspirin, and beta-blockers and occur over the full range of ventricular dysfunction.
• Some evidence from one large RCT indicates that higher doses of an ACE inhibitor may reduce morbidity more than lower doses, with no increase in adverse events.
• Evidence from one observational study indicates that people with heart failure who are not on target doses of ACE inhibitors are more likely to be readmitted to hospital [Luthi et al, 2003].

Angiotensin-II receptor antagonists (AIIRAs)

• The recommendation to give an AIIRA to people who are intolerant of ACE inhibitors is consistent with guidelines from NICE [National Clinical Guideline Centre for Acute and Chronic Conditions, 2010], SIGN [SIGN, 2007], and ESC [European Society of Cardiology, 2008].
• NICE found evidence from five randomized placebo-controlled trials that AIIRAs significantly reduce the rate of hospitalization due to heart failure, and the composite endpoint of cardiovascular mortality and hospitalization due to heart failure. There was no statistically significant reduction in all-cause mortality.
• Although evidence from several large comparative RCTs suggests that there is no difference in efficacy between AIIRAs and ACE inhibitors, ACE inhibitors are preferred to AIIRAs because there is stronger evidence to support their use (placebo-controlled trials of ACE inhibitors have consistently found reductions in mortality).

Beta-blockers

• The recommendation to give a beta-blocker to all people with heart failure and left ventricular systolic dysfunction is consistent with guidelines from NICE [National Clinical Guideline Centre for Acute and Chronic Conditions, 2010], SIGN [SIGN, 2007], and ESC [European Society of Cardiology, 2008].
• Good evidence from large RCTs indicates that beta-blockers reduce mortality and morbidity associated with heart failure. This improvement seems to be independent of the cause or severity of heart failure.
• NICE recommends that beta-blockers should be offered to all people with heart failure due to left ventricular systolic dysfunction, including older people and people with peripheral vascular disease, erectile dysfunction, diabetes mellitus, interstitial pulmonary disease, and irreversible chronic obstructive airway disease. NICE states that these people are often undertreated when they develop heart failure.

Sequencing treatment with beta-blockers and ACE inhibitors

• NICE recommends that treatment may be initiated first with either a beta-blocker or an ACE inhibitor [National Clinical Guideline Centre for Acute and Chronic Conditions, 2010]. This is based on evidence from one RCT which found that people with heart failure had similar outcomes regardless of which treatment was started first. The decision to use one of these two drugs before the other depends on the clinical status of the person (for example blood pressure, heart rate, symptomatic ischaemia, arrhythmias, and other comorbidities).

Aspirin

• Uncertainty remains about the use of aspirin in people with chronic heart failure (without atherosclerotic disease).
• No good RCT evidence is available on the efficacy of aspirin in the management of heart failure. However, there is good evidence that aspirin reduces the risk of cardiovascular events in people with established ischaemic cardiovascular disease or those who are at high risk of cardiovascular disease [Antithrombotic Trialists' Collaboration, 2002], and aspirin is currently recommended for people with cardiovascular disease [British Cardiac Society et al, 2005; National Collaborating Centre for Primary Care, 2008].
• Post-hoc analyses of some of the studies of ACE inhibitors in heart failure have raised concern that aspirin may reduce the beneficial effect of ACE inhibitors, although this has not been confirmed by further analysis.
• NICE recommends that, in the absence of conclusive evidence and general consensus as to the benefits of aspirin in people with atherosclerotic arterial disease, aspirin (75 mg to 150 mg once daily) should be prescribed for people with heart failure and atherosclerotic arterial disease (including coronary heart disease) [National Clinical Guideline Centre for Acute and Chronic Conditions, 2010].
• SIGN concludes that there is no firm evidence to support the use or withdrawal of aspirin in people with chronic heart failure [SIGN, 2007].
• The ESC guidelines conclude that there is no evidence that antiplatelet drugs reduce atherosclerotic risk in people with heart failure [European Society of Cardiology, 2008].

Warfarin

• The recommendation to prescribe anticoagulation for people with heart failure and atrial fibrillation is based on NICE guidance on atrial fibrillation [National Collaborating Centre for Chronic Conditions, 2006].
• The recommendation to prescribe anticoagulation to people with heart failure in sinus rhythm who have a history of thromboembolism, left ventricular aneurysm, or intracardiac thrombus is a good practice point recommended by NICE [National Clinical Guideline Centre for Acute and Chronic Conditions, 2010].

Statins

• NICE recommends that people with heart failure should receive statins only in accordance with current indications (if the person has atherosclerotic arterial disease or has a 10-year risk of a cardiovascular event which is 20% or more).
• Evidence from several randomized placebo-controlled trials, and a subsequently published meta-analysis of these trials, suggests that statins do not decrease all-cause mortality or cardiovascular mortality in people with heart failure. However, results from the meta-analysis indicate that statins may increase left ventricular ejection fraction and decrease hospitalization for worsening heart failure.

Referral

• The recommendation that people who remain symptomatic despite optimal treatment with a diuretic, an ACE inhibitor (or AIIRA), and a beta-blocker should be referred for specialist assessment and management is based on guidelines published by NICE [National Clinical Guideline Centre for Acute and Chronic Conditions, 2010].
• People at this stage usually have severe heart failure and are likely to benefit from specialist opinion.
• There is no clear evidence regarding the most appropriate drug to use next in such people.
• The addition of another drug at this stage greatly increases the risk of adverse effects, with less clear evidence of benefit.
• Other therapeutic options may be available, such as cardiac resynchronisation therapy and implantable cardioverter-defibrillators.

Specialist

• NICE defines the term 'specialist' as a physician with sub-speciality interest in heart failure (often a consultant cardiologist) who leads a specialist multidisciplinary heart failure team of professionals with appropriate competencies from primary and secondary care. The team will involve, where necessary, other services (such as rehabilitation, tertiary care, and palliative care) in the care of individual persons.

These recommendations reflect the National Institute for Health and Clinical Excellence (NICE) guideline Chronic heart failure: national clinical guideline for diagnosis and management in primary and secondary care [National Clinical Guideline Centre for Acute and Chronic Conditions, 2010] and are in line with international guidelines [ICSI, 2007; SIGN, 2007; European Society of Cardiology, 2008].

Functional capacity

• The New York Heart Association (NYHA) classification of functional capacity has been widely used over many decades, both in research and clinical practice. The current version is the result of a series of updates to the 1928 classification [American Heart Association, 1994]. It aims to provide a standard and more objective way of describing severity of symptoms.
• A UK survey of 30 cardiologists found that they had no consistent method for assessing NYHA class [Raphael et al, 2006]. The same report included a study of inter-operator variability among four cardiologists assessing 50 people. The average concordance between any pair of cardiologists was 54%, and there was very poor agreement in differentiating between class II and class III. The authors considered the NYHA classification to be useful despite these limitations and recommended that the objectivity of the classification be improved by clarifying how 'ordinary physical activity', 'slight limitation', and 'marked limitation' are elicited from people.

Fluid status

• Fluid status should be determined because this allows response to treatment to be assessed and guides further management.

Assessing cardiac rhythm

• It is important to regularly and routinely assess cardiac rhythm because people with heart failure frequently have treatable arrhythmias (especially atrial fibrillation), and these can be discovered at any time before, at, or after the initial presentation with heart failure.
• If symptoms deteriorate and the pulse is regular, electrocardiography should be considered because atrial tachycardia can be regular and may be missed on clinical examination.
• For more information, see Complications.

The recommendations for referral reflect the National Institute for Health and Clinical Excellence (NICE) guideline Chronic heart failure: national clinical guideline for diagnosis and management in primary and secondary care [National Clinical Guideline Centre for Acute and Chronic Conditions, 2010] and are largely based on expert opinion.

Specialist

• NICE defines the term 'specialist' as a physician with sub-speciality interest in heart failure (often a consultant cardiologist) who leads a specialist multidisciplinary heart failure team of professionals with appropriate competencies from primary and secondary care. The team will involve, where necessary, other services (such as rehabilitation, tertiary care, and palliative care) in the care of individual persons.

These recommendations reflect recommendations in the National Institute for Health and Clinical Excellence (NICE) guideline Chronic heart failure: national clinical guideline for diagnosis and management in primary and secondary care [National Clinical Guideline Centre for Acute and Chronic Conditions, 2010], as well as guidelines from the Scottish Intercollegiate Guidelines Network (SIGN) [SIGN, 2007] and European Society of Cardiology guidelines [European Society of Cardiology, 2008].

Recognizing the symptoms of heart failure

• The recommendation to teach people how to recognize the symptoms of heart failure is largely based on expert opinion [European Society of Cardiology, 2008].

How to monitor body weight

• The recommendation to teach people to monitor their weight is largely based on expert opinion [SIGN, 2007; European Society of Cardiology, 2008].
• Evidence from one study indicates that increases in body weight are not always associated with a deterioration of symptoms of heart failure and fluid retention [Lewin et al, 2005].

Keeping active and fit

• Keeping active and fit is generally recommended — see the CKS topic on CVD risk assessment and management. This may be even more important for people with heart failure and is widely recommended by experts on the basis of experience and evidence of benefit that is not always consistent [ICSI, 2007; SIGN, 2007; European Society of Cardiology, 2008; National Clinical Guideline Centre for Acute and Chronic Conditions, 2010].
• Older systematic reviews found small studies providing evidence that exercise reduces mortality and hospitalization, and improves exercise tolerance and health-related quality of life [Piepoli et al, 2004; Rees et al, 2004; Smart and Marwick, 2004].
• Two more recent randomized controlled trials (RCTs) in people with chronic heart failure suggest that intensive aerobic exercise may be more effective than less intensive exercise and weight training [Feiereisen et al, 2007; Wisloff et al, 2007].
• A small RCT found that 6 years after participation in a residential rehabilitation programme, people with chronic heart failure had slightly better outcomes than the control group, maintained exercise capacity, and engaged in activities that exceed the minimal amount recommended by guidelines for cardiovascular health [Mueller et al, 2007].
• A large RCT (1159 participants) found that exercise training resulted in a nonsignificant reduction in the risk of death (from any cause) or hospitalization, and a small but statistically significant improvement in self-reported health status [Flynn et al, 2009; O'Connor et al, 2009].
• A systematic review on the effects of moderate- to high-intensity resistance training in people with chronic heart failure found 10 trials, all with methodological flaws [Spruit et al, 2009]. The review concluded that the evidence on benefits was weak and inconsistent and that there was no evidence of harm.

Stopping smoking

• Stopping smoking is recommended for everyone — see the CKS topic on Smoking cessation. It may be even more important for people with heart failure.
• The effect of smoking cessation in people with heart failure has not been studied in clinical trials. However, current smoking was an independent predictor of readmissions for heart failure in two observational studies [Evangelista et al, 2000; Suskin et al, 2001].

Prudent use of alcohol

• Prudent use of alcohol is generally recommended — see the CKS topic on Alcohol - problem drinking. It may be even more important for people with heart failure.
• A recent review [Djousse and Gaziano, 2008] found:
• Good evidence that heavy alcohol use is associated with cardiomyopathy and that abstinence leads to improved survival.
• Limited evidence that moderate alcohol use reduces the risk of heart failure compared with abstinence.
• No evidence on the type of beverage and heart failure, or on drinking patterns (binge drinking versus frequent light to moderate drinking) and heart failure.

Losing excess weight and maintaining weight loss

• Losing excess weight and maintaining weight loss are generally recommended — see the CKS topic on Obesity.
• Losing excess weight is thought to be important for people with heart failure, although there is little evidence to support this assumption [Kenchaiah et al, 2007; Abdulla et al, 2008; Shirley et al, 2008].

Restricting salt consumption

• The recommendation to restrict salt consumption is largely based on expert opinion and extrapolation from evidence of the effects of salt consumption on hypertension [SIGN, 2007; European Society of Cardiology, 2008].
• Two RCTs of low-salt diets in people with heart failure found weak evidence for modest benefits in terms of weight loss, oedema, fatigue, quality of life, and New York Heart Association classification of heart failure [Alvelos et al, 2004; Colin Ramirez et al, 2004].

Restricting fluid intake

• The recommendation to restrict fluid intake in people with severe symptoms of heart failure is largely based on expert opinion [SIGN, 2007; European Society of Cardiology, 2008].
• One open-label RCT in people hospitalized for severe heart failure symptoms failed to find evidence of benefit from fluid restriction [Travers et al, 2007]. Nevertheless, there is no concern that fluid restriction to 1.5–2 L per day could be harmful.

Diarrhoea and vomiting

• The recommendation to stop treatment with an ACE inhibitor, AIIRA, diuretic, or spironolactone for a short time (1–2 days) is based on concern that continued treatment may increase the risk of acute renal failure [Stirling et al, 2003; McGuigan et al, 2005], and CKS expert reviewers (based on pharmacological and physiological knowledge of drug effects on the kidney).

Immunizations

• The recommendation for influenza and pneumococcal immunization is largely based on expert opinion and extrapolation from the benefits of these immunizations in other populations at risk — see the CKS topics on Immunizations - seasonal influenza and Immunizations - pneumococcal.
• A large epidemiological study in elderly people found that immunization against influenza was associated with reductions in the risk of hospitalization for heart disease, cerebrovascular disease, and pneumonia or influenza, as well as the risk of death from all causes during influenza seasons [Nichol et al, 2003].

• This information is from the Driver and Vehicle Licensing Agency [DVLA, 2010].

These recommendations and information are in line with recommendations in the National Institute for Health and Clinical Excellence (NICE) guideline Chronic heart failure: national clinical guideline for diagnosis and management in primary and secondary care [National Clinical Guideline Centre for Acute and Chronic Conditions, 2010], as well as European professional association guidelines [European Society of Cardiology, 2008].

Risk of sexual activity

• The recommendation to counsel people about sexual activity and the advice on the safety of sexual activity are largely based on expert opinion [European Society of Cardiology, 2008] and a consensus development panel [Jackson et al, 2006].

Interaction between nitrates/nicorandil and phosphodiesterase inhibitors

• The combination of a phosphodiesterase inhibitor and a nitrate (including amyl nitrite) or nicorandil can result in excessive hypotension and possibly precipitate myocardial infarction [Baxter, 2010].
• The interaction with phosphodiesterase inhibitors is well established and clinically significant.
• It is not yet established whether nicorandil interacts with phosphodiesterase inhibitors to the same extent, but the manufacturers recommend that its use is contraindicated with phosphodiesterase inhibitors.

• These recommendations are based on published expert opinion from the Working Group of the British Cardiovascular Society, Fitness to fly for passengers with cardiovascular disease [Smith et al, 2010].
• Commercial airline passengers breathe air with a reduced oxygen content that results in low blood oxygen saturations, which may be expected to have adverse effects on people with heart failure. There is little evidence regarding the effects of hypoxia in people with heart failure. The Working Group of the British Cardiovascular Society found evidence from three small trials that [Smith et al, 2010]:
• In people with stable heart failure, including New York Heart Association (NYHA) class III or IV, short-term (up to 1 hour) hypoxia at rest produces no significant adverse effects.
• People with mild to moderate stable heart failure (NYHA class II) can tolerate up to 7 hours of hypoxia at rest.
• The Working Group of the British Cardiovascular Society did not find evidence that in-flight oxygen prevents adverse effects in people with heart failure. However, the Working Group recommended that access to in-flight oxygen should be available for passengers who have severe heart failure (NYHA class IV). They also state that availability of in-flight oxygen should be considered for people with NYHA class III.

• This information is in line with recommendations in the National Institute for Health and Clinical Excellence (NICE) guideline Chronic heart failure: national clinical guideline for diagnosis and management in primary and secondary care [National Clinical Guideline Centre for Acute and Chronic Conditions, 2010], as well as Scottish national guidelines and European professional association guidelines [SIGN, 2007; European Society of Cardiology, 2008]. These guidelines strongly emphasize the importance of providing information to affected individuals, their family, and carers.