4 Research recommendations

The Guideline Development Group has made the following recommendations for research, based on its review of evidence, to improve NICE guidance and patient care in the future.

4.1 Beta-blockers and angiotensin-converting enzyme inhibitors for heart failure with preserved left ventricular ejection fraction

What is the effectiveness of angiotensin-converting enzyme (ACE) inhibitors and beta-blockers (given either alone or in combination) compared with placebo in patients with heart failure and preserved left ventricular ejection fraction?

Why this is important

At least half of people with heart failure in the community have preserved left ventricular ejection fraction. Research has focused on heart failure with left ventricular systolic dysfunction and found several agents to be beneficial (notably ACE inhibitors, beta-blockers and aldosterone antagonists). To date, studies of treatment in patients with preserved left ventricular ejection fraction have found no significant benefit. However, there is limited evidence that suggests potential benefit of both beta-blockers and ACE inhibitors in this population. The equivocal evidence base for beta-blockers and ACE inhibitors needs to be explored in greater depth to establish whether there is definite benefit or not. This is particularly important because of the extent of heart failure with preserved left ventricular ejection fraction in the general population.

4.2 Home telemonitoring, natriuretic peptide-guided therapy and formal follow-up by a heart failure team

What is the effectiveness and cost effectiveness of home telemonitoring, monitoring of serum natriuretic peptides and formal follow-up by a heart failure team for patients with heart failure due to left ventricular systolic dysfunction?

Why this is important

Heart failure is characterised by repeated hospitalisation. For people with left ventricular systolic dysfunction, hospitalisation can be reduced by appropriate treatment and organised nursing care. Recent studies of ways to prevent hospitalisation have focused on telemonitoring (the patient's status is assessed in the patient's own home) and the use of serum natriuretic peptide levels (to guide uptitration of drugs) compared with 'usual' care. The studies used various research methods and differing levels of 'usual' care, which makes it difficult to compare the results. It has been suggested that, when care is delivered by an organised heart failure team under consultant supervision, additional strategies such as telemonitoring and monitoring of serum natriuretic peptides may not confer advantage. Further research is important to ascertain whether monitoring and supervision techniques afford advantage over formal, organised care by a specialist multidisciplinary heart failure team.

4.3 The role of natriuretIc peptides in the management and prognosis of heart failure

What is the optimal use of natriuretic peptides in the management and prognostic stratification of patients with heart failure?

Why this is important

Heart failure is characterised by repeated hospitalisation, high mortality in the period immediately following hospitalisation and an unpredictable course in the later stages. In people with heart failure, natriuretic peptide levels have been shown to correlate with poor prognosis. Studies of the use of natriuretic peptides to guide drug titration have suggested a potential reduction in mortality in some groups, although the overall utility of this remains uncertain in the broader population with heart failure. Research is needed in three areas:

  • Whether elevated natriuretic peptides despite maximum tolerated therapy could be used to predict prognosis and to guide an 'end-of-life' strategy for late-stage heart failure.

  • Whether the level of natriuretic peptides at the time of discharge could be used to prioritise routine follow-up after discharge.

  • Whether routine monitoring of natriuretic peptides in people with heart failure in the community might allow optimal use of community nursing resources.

4.4 Aldosterone antagonists and angiotensin II receptor antagonists in heart failure

What is the comparative effectiveness of aldosterone antagonists and angiotensin II receptor antagonists (ARBs) in symptomatic patients with heart failure due to left ventricular systolic dysfunction who are:

  • on optimal therapy with a beta-blocker and an ACE inhibitor, or

  • on a beta-blocker but are intolerant of ACE inhibitors?

Why this is important

Inhibition of the renin-angiotensin-aldosterone system with an ACE inhibitor in combination with a beta-blocker is currently the cornerstone of the management of heart failure with left ventricular systolic dysfunction.

The first question is which antagonist of the renin-angiotensin-aldosterone system should be added if the patient remains symptomatic despite being on optimal therapy with a beta-blocker and an ACE inhibitor?

In trials, both aldosterone antagonists and ARBs have been used in addition to ACE inhibitors for patients with heart failure who remain symptomatic. However, there are no trials comparing the effectiveness and safety of adding aldosterone antagonists or ARBs to otherwise optimal therapy.

The second question concerns the comparative effectiveness of aldosterone antagonists and ARBs in patients (at least 10%) who are intolerant of ACE inhibitors. An ARB may be less effective than an ACE inhibitor. Aldosterone antagonists have been shown to be beneficial in patients with heart failure due to left ventricular systolic dysfunction but most were taking an ACE inhibitor. It is important to know which is the most effective method for inhibition of the renin-angiotensin-aldosterone system when ACE inhibitors are not tolerated: an aldosterone antagonist in combination with a beta-blocker or an ARB in combination with a beta-blocker.

4.5 Hydralazine in combination with nitrate for heart failure with preserved left ventricular ejection fraction

What is the comparative effectiveness of vasodilator therapy with nitrates and hydralazine in patients with heart failure and preserved left ventricular ejection fraction?

Why this is important

More than half of people with heart failure in the community have preserved left ventricular ejection fraction. To date, studies have not shown that ARBs, ACE inhibitors or beta-blockers afford significant prognostic benefit for this population. In patients with heart failure due to left ventricular systolic dysfunction, studies have indicated that the combination of nitrate and hydralazine improves prognosis.

The pathophysiology of heart failure with preserved left ventricular ejection fraction is not clearly understood. However, hypertension is common, arterial compliance may play a major part and increased preload is a potential problem contributing to this form of heart failure. Hydralazine is an arterial vasodilator, and nitrates may reduce preload. Research is needed to investigate whether using these drugs in combination would benefit patients with heart failure and preserved left ventricular ejection fraction.

  • National Institute for Health and Care Excellence (NICE)