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.