How medication reviews make one-stop general practice work
Dr Strat Liddiard details the latest evidence on management of a condition that now affects nearly 2 per cent of the population
Some 40 per cent of patients die within 12 months of being diagnosed with heart failure. Subsequent mortality is about 10 per cent a year – a rate similar to colon cancer and worse than breast or prostate malignancy. Heart failure is prevalent in
1-2 per cent of the whole population and a further 1-2 per cent have undiagnosed asymptomatic systolic left ventricular dysfunction (SLVD). Most of these are over 75; 6 per cent are aged 75-85 and in the over-85s the figure rises to 10 per cent.
Treating heart failure costs the NHS about £700 million a year – 2 per cent of its total budget. About £500 million of this is spent on inpatient hospital care. But this figure could be greatly reduced by pre-emptive medical care.
The NICE definition of heart failure is a complex syndrome that can result from any structural or functional cardiac disorder that impairs the ability of the heart to support a physiological circulation. It is characterised by breathlessness, fatigue and fluid retention1. The NICE definition is an attempt to encapsulate a syndrome where the symptoms and signs do not lead us to the diagnosis and the pathology does not lead us to the symptoms and signs.
Diagnosing heart failure
The NICE diagnostic algorithm in box 1 (page 44) shows investigations that are necessary for all patients with breathlessness, tiredness and ankle oedema. These start with an ECG and where available b-type natriuretic peptide (BNP) test. Those with an abnormal result should have echocardiography.
GPs can find ECGs difficult to interpret and these alone should not be regarded as an effective exclusion test for heart failure if there is a reason for further
investigation. Additional tests might include chest X-ray, lung function and blood tests for patients suffering from breathlessness. Such tests will not confirm a diagnosis of chronic heart failure, however.
The BNP test
The BNP test can be used to rule out heart failure. BNP is a natriuretic peptide predominantly released by the left ventricle when it is stretched. Two biochemical measurements can be made: N-terminal pro-BNP, which is measured in the laboratory, and BNP which can be measured on a portable device in the home or the GP's surgery. Both can be used as tests in new patients to exclude heart failure.
Unless the local health provider will provide unlimited echocardiography, BNP will have a major role in screening out non-cardiac problems. There is a powerful argument for extending this to screening patients at high risk of SLVD.
Plasma BNP levels are higher in those with more severe heart failure. It is an independent predictor of death in patients with chronic heart failure (and acute heart failure). This correlation may help to identify patients with severe heart failure on maximal therapy who are approaching the terminal phase of the illness.
Trials are in progress to examine the use of BNP in guiding treatment decisions. There are no universally agreed non-invasive diagnostic test criteria and this is where the BNP test may come into its own.
Treating heart failure
Establishing the cause
Having established the diagnosis the cause of the heart failure must be identified. Although most cases are caused by SLVD due to ischaemia or hypertension, a significant minority may be caused by diastolic dysfunction.
A recent paper reviewed eight published studies of diastolic dysfunction diagnosed on echocardiographic criteria and found a 16-fold difference in the prevalence2.
There is no treatment that is proven to be beneficial in diastolic dysfunction. The diagnosis should be made with great caution and the patient managed symptomatically. Other rarer causes must be kept in mind, particularly in the younger patient. Heart failure in the absence of an obvious cause is an indication for referral.
ACE inhibitors and angiotensin-II receptor antagonists (ARBs)
The NICE treatment algorithm is outlined in box 2. The evidence for ACE inhibitors is widely accepted but GPs remain reluctant to increase the dose to the maximum recommended. I find using titration packs useful to achieve maximum dosage.
The case for ARBs (the sartans) was equivocal until the CHARM studies were published last year. There were three arms to the CHARM study, outlined in box 3.
When the three trials are analysed together6 there is a reduction in cardiovascular mortality and a marked reduction in heart failure hospitalisation. This study provided the evidence to support the long-held belief that ARBs are useful in patients who are intolerant of ACE inhibitors. The questions about adding ARBs to ACE inhibitors and using them in symptomatic patients with no evidence is less clear. More work is needed to try to identify which patients benefit – for undoubtedly some do.
It flies in the face of years of indoctrination but some ß-blockers are undoubtedly good for heart failure. The recent carvedilol or metoprolol European trial (COMET7) compared two of the drugs suggested to be of benefit in previous studies. Patients (1,518) on metoprolol, a selective ß1 antagonist, fared less well than those taking carvedilol, a non-specific ß1 and ß2 blocker with some a blocking properties.
Although there were criticisms of the study it seems the two main contenders in this country for use in heart failure are carvedilol and bisoprolol. Other studies show an increasing response with increasing doses in carvedilol but not bisoprolol – so it is important to achieve the maximum dose if using the former.
Once the patient is on the maximum doses of diuretic, ACE inhibitor and ß-blocker but still has problems it is time to consider other drugs. Digoxin improves symptoms but has no effect on prognosis and I find it particularly useful in patients with atrial fibrillation or hypotension and exhaustion.
Spironolactone has been shown to be beneficial but has side-effects. A new drug, eplerinone, which is a selective aldosterone antagonist, has been tested8. Some 6,632 patients with heart failure or left ventricular dysfunction following a myocardial infarction were randomised to placebo or eplerinone therapy in addition to conventional treatment. There was a 15 per cent decrease in all-cause mortality in the eplerinone group9.
The companion study on eplerinone mentioned suggests biventricular pacing or resynchronisation therapy with or without an implantable defibrillator is of great value in some patients with severe left ventricular dysfunction. This is a relatively expensive therapy and funding may be an issue.
There has been some excitement about revascularisation in patients who do not have angina. There is no evidence to support this but the HEART-UK trial should answer the question. A meta-analysis of smaller studies has shown exercise is good for heart failure patients and many rehabilitation teams are looking to develop programmes for these patients.
The way forward
Much progress has been made in treating heart failure but much more needs to be done in turning the research into everyday practice in the UK. We need to find SLVD sooner and treat it more aggressively. This needs to happen in the community, not in hospitals.
When there is nothing else to be done medically to sustain life, patients and their relatives need support and help of the sort given to people dying of cancer. This has been lacking but the need is recognised and recent collaboration between cardiologists, GPs and the palliative care teams across the country are moving this forward.
Strat Liddiard is national clinical lead for the CHD collaborative and a GP in Poole, Dorset
Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity (CHARM)
Mortality and morbidity (CHARM)
The CHARM alternative trial
2,028 patients with heart failure due to SLVD and who were
intolerant of ACE inhibitors were randomised to placebo or candesartan. There was unequivocal improvement in mortality and hospitalisation in the treated group3.
The CHARM added trial
2,548 patients with heart failure due to SLVD already receiving an ACE inhibitor were randomised to placebo or candesartan. There was a small
but significant reduction in the end-point of cardiovascular death or hospitalisation for heart failure but no change in the all-cause mortality4.
The CHARM preserved trial
3,023 patients with symptoms of heart failure but no evidence of SLVD were randomised to placebo or candesartan. There was no effect on mortality but a reduction in admissions for heart failure in the candesartan group5.
1 National Institute for Clinical Excellence. Chronic heart failure; national clinical guideline for diagnosis and management in primary and secondary care. www.nice.org.uk
2 Petrie MC et al. Poor concordance of commonly used echocardiographic measures of left ventricular diastolic function: is there a reliable echocardiographic measure of diastolic dysfunction? Heart 2004;90:511-17
3 Granger CB et al. Effects of candesartan in patients with chronic heart failure and reduced left-ventricular systolic function intolerant to ACE inhibitors: the CHARM alternative trial. Lancet 2003; 362:772-76
4 McMurray JJV et al. Effects of candesartan in patients with chronic heart failure and reduced left-ventricular systolic function taking ACE inhibitors: the CHARM added trial. Lancet 2003; 362: 767-77-1
5 Yusuf S et. Al. Effects of candesartan in patients with chronic heart failure and preserved left-ventricular ejection fraction: the CHARM-Preserved trial. Lancet 2003; 362: 777-81
6 Pfeiffer MA et al. Effects of candesartan on mortality and morbidity in patients with chronic heart failure: the CHARM overall programme. Lancet 2003; 362:759-66
7 Poole-Wilson PA et al. Comparison of carvedolol and metoprolol on clinical outcomes in patients with chronic
heart failure in the Carvedolol Or Metoprolol European
Trial (COMET): randomised controlled trial.
Lancet 2003 362: 7-13
8 Zannad F et al. Eplerinone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS). NEJM 2003 348; 1309-21
9 Bristow M et al. Cardiac-Resynchronisation Therapy with or without an Implantable Defibrillator in Advanced Chronic Heart Failure. NEJM 350:2140-2150
•In addition there are booklets for patients from the British Cardiac Patients Association at
•And a Government guide at