2009 Edition Developed by Professor Martin R Cowie National Heart and Lung Institute, Imperial College, London
Chronic heart failure
A complex syndrome that can result from any structural or functional cardiac disorder that impairs the pumping ability of the heart Most common cause is left ventricular muscle damage Various conditions may predispose to, or cause, such muscle damageBACKGROUND
Characterising the heart failure syndrome
Symptoms and signs Severity of syndrome Underlying cardiac abnormalities Aetiology of cardiac abnormality Precipitating and exacerbating factors Identification of relevant co-morbidities Estimation of prognosisBACKGROUND
Heart failure is not in itself a complete diagnosis. It is important to characterise the syndrome by:
Symptoms and signs of heart failure (1)
Symptoms Shortness of breath on exertion Decreased exercise tolerance (often simply 'fatigue') Paroxysmal nocturnal dyspnoea Orthopnoea Ankle swellingBACKGROUND
NICE, 2003; CKS
Symptoms and signs of heart failure (2)
Signs The most specific signs are: Laterally displaced apex beat Elevated jugular venous pressure Third heart sound Less specific signs include: Tachycardia Lung crackles (usually at bases) Hepatic engorgement (tender hepatomegaly) Peripheral oedema
BACKGROUND
NICE, 2003; CKS
The NYHA classification
Class INo limitations on activity. No fatigue, breathlessness or palpitation on ordinary physical activity
Annual mortality 3-5%
Class II
Patients are comfortable at rest but ordinary physical activity such as climbing stairs or doing housework results in symptoms
‘Mild’ heart failure Annual mortality 10%
Class III
Patients have a marked limitation of physical activity. Although patients are comfortable at rest, less than ordinary physical activity will lead to symptoms
‘Moderate’ heart failure Annual mortality 12-16%
Class IV
Patients have symptoms even at rest and are unable to undertake any physical activity without discomfort
‘Severe’ heart failure Annual mortality 15-20%
BACKGROUND
Adapted from ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure; Eur Heart J, 2008
Relevant history
Ischaemic heart disease: angina; myocardial infarction Hypertension Atrial fibrillation Valvular heart disease Diabetes mellitus Renal dysfunction Chronic lung disease
BACKGROUND
Coronary artery disease is the leading cause of heart failure
Adapted from Fox et al, Eur Heart J, 2001BACKGROUND
Full investigation (including coronary angiography) in new patients aged <75 in a UK population-based study
Coronary artery disease (52%)
Hypertension alone (4%)
Valve disease (10%)
Alcohol (4%)
AF alone (3%)
Other (5%)
Idiopathic (no CAD) (13%)
Undetermined (no angiographic data) (10%)
Epidemiology and health service impact
An Educational Slide Set Developed by Professor Martin R Cowie National Heart and Lung Institute, Imperial College, LondonThe Incidence of Heart Failure The Hillingdon Heart Failure Study
02
4
6
8
10
12
14
16
18
25-34
35-44
45-54
55-64
65-74
75-84
85+
Men
Women
Incidence (new cases/1000 population/year)
Age group (years)
Cowie et al, Eur Heart J, 1999
Median age at first presentation is 76 years
EPIDEMIOLOGY AND HEALTH SERVICE IMPACT
Adapted from Cowie et al. 1999.
The Prevalence of Heart Failure The Echocardiographic Heart of England Study
05
10
15
20
25
45-54
55-64
65-74
75-84
85+
Men
Women
Percentage with definite heart failure
Age group (years)
Davies et al, Lancet, 2001
EPIDEMIOLOGY AND HEALTH SERVICE IMPACT
Adapted from Davies et al. 2001.
552 incident cases followed up to March 2002; 338 deaths
Cowie et al, Heart, 2000EPIDEMIOLOGY AND HEALTH SERVICE IMPACT
The poor prognosis of heart failure London Heart Failure Study
Analysis time (years)
Median survival: 3 years from diagnosis
1.00
0.75
0.50
0.25
0.00
0
2
4
6
8
Survival
Adapted from Cowie et al. 2000.
The prognosis is as bad as for many cancers
British Heart Foundation, 2002
Non-Hodgkins Lymphoma
0
20
40
60
80
100
Pancreas
Lung
Oesophagus
Stomach
Leukaemia
Kidney
Ovary
Heart failure
Colon
Prostate
Bladder
Uterus
Breast
Skin
One year survival rate %
EPIDEMIOLOGY AND HEALTH SERVICE IMPACT
Adapted from British Heart Foundation et al. 2002.
Survival may be improving (1) United States data (1950-1999)
EPIDEMIOLOGY AND HEALTH SERVICE IMPACTLevy et al, N Engl J Med, 2002
Adapted from Levy et al. 2002.
Adapted from Levy et al. 2002.
Survival may be improving (2) England (Leicestershire)
Hazard ratio of death according to year of first hospital admission for heart failure (1993/4 as baseline)Blackledge et al, Heart, 2003;
EPIDEMIOLOGY AND HEALTH SERVICE IMPACT
Adapted from Blackledge et al. 2003.
Survival may be improving (3) Scotland
EPIDEMIOLOGY AND HEALTH SERVICE IMPACTJhund et al, Circulation, 2009
Trend in median survival (excluding deaths within 30 days), 1986-2003
Adapted from Jhund et al. 2009.
Admission rates in England (1990/91 to 1999/2000)Heart failure admission rates per 1000 population for those aged 45 years British Heart Foundation, 2002
EPIDEMIOLOGY AND HEALTH SERVICE IMPACT
0
0.2
0.4
0.6
0.8
1
1.2
1.4
1.6
1.8
2
1990/91
1992/93
1994/95
1996/97
1998/99
Men
Women
Admission rates per 1000
Adapted from British Heart Foundation et al. 2002.
Trend to reduced admission rates Scotland: 1986-2003
EPIDEMIOLOGY AND HEALTH SERVICE IMPACTJhund et al, Circulation, 2009
Adapted from Jhund et al. 2009.
Heart failure related hospital admissions are long
British Heart Foundation, 20020
5
10
15
20
25
30
All diagnoses
All circulatory
Coronary Heart Disease
Angina
Acute MI
Heart failure
Stroke
Diabetes
All cancer
All nervous system
All respiratory system
All digestive system
All GU system
Complications of pregnancy & childbirth
Injuries and poisoning
Average duration of hospital admission (days)
EPIDEMIOLOGY AND HEALTH SERVICE IMPACT
Adapted from British Heart Foundation et al. 2002.
Cost is high and driven by inpatient care
British Heart Foundation, 2002Total cost approx 2% of annual NHS budget
(11-13 visits per year)
EPIDEMIOLOGY AND HEALTH SERVICE IMPACT
Outpatient investigation 6%
Outpatient care 8%
Drugs 9%
Primary Care 17%
Inpatient care 60%
Adapted from British Heart Foundation et al. 2002.
Many patients remain symptomatic even at time of discharge from hospital
Prospective Outcomes Study in Heart Failure (POSH): 300 patients admitted with decompensated HF to European centres, 2002/30%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
Admission
Discharge
I
II
III
IV
NYHA Class
EPIDEMIOLOGY AND HEALTH SERVICE IMPACT
Cowie et al, Eur Heart J, 2007
Adapted from Cowie et al. 2007.
Size of the problem Summary
Common Affects 1-2% of the population Annual incidence is 0.5-1% Serious (but improving) 40% mortality at 1 year, 10% per year thereafter Increasing Ageing population and better treatment of acute MI Disabling Symptoms have enormous impact on quality of life, worse than many other chronic conditions Expensive Around 2% of NHS budget, 5% of acute admissions, and 10% of bed occupancyEPIDEMIOLOGY AND HEALTH SERVICE IMPACT
BMJ, 2002; Eur J Heart Failure, 1999; NICE, 2003; BHF, 2002; DOH 2009
National initiatives
An Educational Slide Set Developed by Professor Martin R Cowie National Heart and Lung Institute, Imperial College, LondonSTANDARD 11Doctors should arrange for people with suspected heart failure to be offered appropriate investigations (e.g. electrocardiography, echocardiography) that will confirm or refute the diagnosis. For those in whom heart failure is confirmed, its cause should be identified – the treatments most likely to both relieve symptoms and reduce their risk of death should be offered. Department of Health, 2000
NATIONAL INITIATIVES
The National Service Framework for Coronary Heart Disease
The National Service Framework for Coronary Heart Disease
TARGETS Every primary care team should ensure that all those with heart failure are receiving a full package of appropriate investigation and treatment, demonstrated by clinical audit data not more than 12 months old Every hospital should offer complete and correct packages of audited effective interventions to all people discharged with a diagnosis of heart failure, demonstrated by clinical audit data no more than 12 months old.Department of Health, 2000
NATIONAL INITIATIVES
Scotland
CHD is a national priorityTarget of a reduction in death rate from CHD in people under 75 by 50% between 1995 and 2010‘Better health, better care’ health action planAction needed to reduce heart failure readmissionsRevised CHD and stroke strategy due in 2009NHS Quality Improvement Scotland (QIS)Clinical standards and a national audit programme for CHD under development NATIONAL INITIATIVESScottish Government, 2007, 2008
The Welsh perspective (1)
The Cardiac Disease National Service Framework for Wales (2008) is the key policy document for the delivery and development of cardiac services in Wales Standard 4 (Managing the care of patients with chronic heart failure) states: “Each person with chronic heart failure and their carers has access to high quality evidence-based assessment, treatment and care services so that their quality of life is improved as much as possible” NATIONAL INITIATIVESWelsh Assembly Government 2008
The Welsh perspective (2)
Key interventions in cardiac disease NSF for Wales relating to heart failure include: Establishing local heart failure teams, based in primary care or hospital, to serve a defined group of general practices. Each local team to be linked to a tertiary heart failure centre GP access to a weekly diagnostic heart failure clinic run by the local heart failure team Patients to have information and support to help them manage their own condition Patients with a confirmed diagnosis should be seen by a heart failure specialist nurse to discuss their management plan All appropriate patients to be offered cardiac rehabilitationNATIONAL INITIATIVES
Welsh Assembly Government 2008
NICE guideline for chronic heart failure England & Wales, 2003 (partial update expected late 2010)
Best practice advice on day-to-day delivery of care for patients with chronic heart failure Diagnostic algorithm Treatment algorithm Monitoring Support after discharge When to refer to a specialist Lifestyle issues Education and support for patients Managing end-of-life issues
NATIONAL INITIATIVES
NICE Guideline Key recommendations for implementation (1)
The basis for historical diagnoses of HF should be reviewed, and only patients with a confirmed diagnosis should be managed according to the guideline Echo should be performed to exclude important valve disease, assess the function of the left ventricle and detect intracardiac shunts All patients with HF due to LVSD should be considered for treatment with an ACE inhibitor Beta-blockers licensed for use in HF should be initiated in patients with HF due to LVSD after diuretic and ACEI therapy (regardless of whether or not symptoms persist)NATIONAL INITIATIVES
NICE, 2003
5. All patients require monitoring, which should include: A clinical assessment of functional capacity, fluid status, cardiac rhythm and cognitive and nutritional status A review of medication, including need for changes and possible side-effects Serum urea, electrolytes and creatinine 6. Patients should generally be discharged from hospital only when their clinical condition is stable and the management plan is optimised 7. The primary care team, patient and carer must be aware of the management plan 8. Management of HF should be seen as a shared responsibility between patient and healthcare professional
NATIONAL INITIATIVES
NICE Guideline Key recommendations for implementation (2)
NICE, 2003
SIGN guideline for chronic heart failure Scotland, 2007
National clinical guideline Diagnostic tests Behavioural modification Pharmacological treatment Interventional procedures Models of care Palliative careSIGN, 2007
NATIONAL INITIATIVES
The General Medical Services Contract (GMS) for primary care
NHS Employers/General Practitioners Committee, 2009Links practice income to achievement of evidence-based and measurable clinical targets in chronic disease management Maximum 1000 points on offer in key quality domains: Clinical (697 points) Organisational (167.5 points) Patient experience (91.5 points) Additional services (44 points) This is payment for work that many practices already undertake
NATIONAL INITIATIVES
Cardiovascular diseases have a high priority in the QOF
NATIONAL INITIATIVESNHS Employers/General Practitioners Committee, 2009
QOF points
Secondary prevention of CHD
87
Primary prevention of CHD (new addition 2009)
13
Heart failure
29
Stroke and TIA
24
Hypertension
81
Diabetes
100
Atrial fibrillation
27
Smoking
60
Heart failure clinical indicators in QOF
NHS Employers/General Practitioners Committee, 2009Indicator
Points
Payment stages
HF1: Register of patients with heart failure
4
HF2: Patients with diagnosis of heart failure confirmed by echocardiogram or by specialist assessment
6
40-90%
HF3: Patients with heart failure due to LVD treated with an ACE inhibitor or ARB
10
40-80%
HF4: Patients with heart failure due to LVD treated with an ACE inhibitor or ARB who are also treated with a beta-blocker
9
40-60%
NATIONAL INITIATIVES
Adapted from NHS Employers/General Practitioners Committee, 2009.
How are we doing? Heart failure service review
Healthcare Commission, 2007
NATIONAL INITIATIVES
Healthcare Commission (HCC) review to assess progress in developing services for heart failureData for 2005/6 from PCTs and Acute Trusts (England)Local services assessed against NSF standards and NICE guideline, plus health care professionals’ and patients’ views on what is important Covers services to patients with suspected or confirmed heart failure due to left ventricular dysfunction
HCC assessment framework
Outcome levelCriteria level
Question themes
Delivery of effective heart failure services
Readmission rates Mortality rates National audit milestones
Patients with suspected heart failure are being effectively diagnosed
Patients are receiving evidence-based treatment consistent with NICE guidelines and are being monitored effectively to ensure optimum treatment and quality of life.
There are adequate and effective multidisciplinary services and care processes in place, which provide patients and carers with adequate education and support
Services are having a positive impact on hospital admissions, mortality and patient experience
Confirmation of diagnosis Rapid access to diagnosis
Prescribing rates Monitoring arrangements
Access to specialist services Structured care processes End of life care Education and support
NATIONAL INITIATIVES
Final results for communities
Diagnosis Treatment and monitoring Multidisciplinary services and care, education & support Hospital admissions, mortality and patient experienceNATIONAL INITIATIVES
Healthcare Commission, 2007
Adapted from Healthcare Commission et al. 2007.
National heart failure audit
NHS Information Centre, 2008NATIONAL INITIATIVES
Adapted from NHS Information Centre 2008.
‘High Quality Care For All’ - the Darzi review Empowers staff and gives patients choiceHealth care will be: Personalised and fairInclude the most effective treatments within a safe systemHelp patients to stay healthyNo new central targetsPower devolved to SHAsInvestment in wellbeing and prevention services e.g. “Reduce your risk” campaign to raise awareness of free vascular checks for 40-74 year olds “Vision of an NHS that gives patients and the public more information and choice, works in partnership and has quality of care at its heart” NATIONAL INITIATIVES
SHAs charged to achieve vision set out in ‘High Quality Care For All’ The 10 English Strategic Health Authorities are charged with local delivery and target settingAll change to be locally led No new central targetsAccountability will be based on quality of care delivered rather than on set targetsNHS bodies will be required to publish ‘quality accounts’‘Vital signs’ indicators for managing national and local priorities NATIONAL INITIATIVES
Advice on heart failure service delivery
NHS Institute for Innovation and Improvement guide to key characteristics of high quality care for patients with heart failure to help local health communities improve the quality and value of care they deliver NHS Improvement commissioning guide to help development of integrated heart failure services across the care pathway highlights evidence-based practice and measurable outcomesNATIONAL INITIATIVES
NHS Institute for Innovation and Improvement, 2009 NHS Improvement, 2008Diagnosis
An Educational Slide Set Developed by Professor Martin R Cowie National Heart and Lung Institute, Imperial College, LondonChronic heart failure
A complex syndrome that can result from any structural or functional cardiac disorder that impairs the pumping ability of the heartDIAGNOSIS
The diagnosis of heart failure in primary care is often inaccurate
Scotland: Only 41% (32/78) patients prescribed diuretics for heart failure had evidence of LVSD on echocardiography. Wheeldon et al, 1993 London: 26% (40/157) of patients with diagnosis of heart failure made by GP had diagnosis confirmed on further assessment. Cowie et al, 1999 UK: 34% (104/306) of patients with diagnosis of heart failure made by GP had diagnosis confirmed on further assessment. Zaphiriou et al, 2005DIAGNOSIS
5 centres in UK natriuretic peptide study
Why is heart failure so difficult to diagnose?
Symptoms are often non-specific Fatigue, weakness, breathlessness, obesity, nocturia, anorexia, abdominal bloating and discomfort, constipation, and cerebral symptoms may each present in other conditions Clinical signs may be insensitive Signs of fluid retention, raised jugular venous pressure, a displaced apex beat and a third heart sound may each not be present Variable primary care access to cardiac investigations BNP testing EchocardiographyDIAGNOSIS
Other conditions that may present with similar symptoms
ObesityHypoalbuminaemiaChest disease – including of lung, diaphragm or chest wallIntrinsic renal or hepatic diseaseVenous insufficiency in lower limbsPulmonary embolic diseaseDrug-induced ankle swelling (e.g. dihydropyridine calcium channel blockers)Depression and/or anxiety disordersDrug-induced fluid retention (e.g. NSAIDs)Severe anaemia or thyroid diseaseAnginaBilateral renal artery stenosis DIAGNOSISNICE, 2003
Diagnostic recommendations NICE Guideline 2003
Detailed historyClinical examinationExclude other disorders presenting in a similar manner Useful ‘rule out’* tests in patients with new symptoms include:12 lead ECG (if completely normal) and/ornatriuretic peptides (BNP or NTproBNP)If one or both are abnormal a diagnosis of heart failure cannot be excluded and transthoracic echocardiography should be performed to consolidate the diagnosis and provide information on both the nature and degree of cardiac dysfunction DIAGNOSIS*No test for heart failure has 100% negative predictive value: if clinical suspicion remains high then further investigation should be undertaken
NICE, 2003
The NICE algorithm for new diagnosis
DIAGNOSIS
NICE, 2003
Adapted from NICE 2003.
SIGN 2007 diagnostic algorithm
DIAGNOSISIncreased emphasis on natriuretic peptide testing
SIGN, 2007
Adapted from SIGN et al. 2007.
DIAGNOSIS
NICE, 2003A normal ECG is unlikely in heart failure
Anterior Q waves and left bundle branch block in patients with ischaemic heart disease are both good predictors of systolic dysfunctionECG signs of left atrial enlargement or left ventricular hypertrophy may be associated with left ventricular dysfunctionAtrial fibrillation is commonly found in patients with heart failure, and complicates the management decisionsBut minor changes in the ECG are common in the elderly, although the majority do not have heart failureAn abnormal ECG does not confirm the diagnosis – further investigation is needed
Peptides now offer a useful “rule out” testin patients with new symptoms DIAGNOSIS
ROC Curve BNP1 - Specificity
1.00
.75
.50
.25
0.00
Sensitivity
1.00
.75
.50
.25
0.00
AUC = 0.84 [0.79-0.88]
ROC Curve NTproBNP
1 - Specificity
1.00
.75
.50
.25
0.00
Sensitivity
1.00
.75
.50
.25
0.00
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Cut off point of 125 pg/ml for NTproBNP gives 97% NPV
Cut off point of 100 pg/ml for BNP gives 87% NPV
Zaphiriou et al, Eur J Heart Failure 2005
Adapted from Zaphiriou et al. 2009.
Echocardiography is the key imaging method for patients with suspected heart failure
Provides detailed information on the structure and function of the cardiac chambers, valves and pericardium Ejection fraction gives a useful measure of left ventricular systolic function Reports should provide technical information in a clinical context May now be available directly to GP (open access), or as part of a diagnostic clinic Obese patients, and those with chronic lung disease, may require other imaging methods (radio-nuclide; magnetic resonance; trans-oesophageal echocardiography)DIAGNOSIS
NICE, 2003
Cardiac magnetic resonance
Provides valuable information about the structure and function of the heart Provides information about the extent of fibrosis and perfusion abnormalities Particularly useful when echo images are poor due to obesity or chronic obstructive lung disease Specialist referral is usually requiredDIAGNOSIS
NICE, 2003
Picture courtesy of Dr S Prasad, Royal Brompton Hospital
Heart failure with preserved ejection fraction(‘diastolic heart failure’) Often presumed when symptoms and signs of heart failure occur in a patient with preserved left ventricular systolic function (normal ejection fraction/normal end-diastolic volume) at rest More common in the elderly, women and those with hypertension or diabetes Diagnosis remains controversial Echocardiography may help confirm the diagnosis Natriuretic peptides may be helpful in ruling out heart failure in those with preserved ejection fraction
DIAGNOSIS
ESC, 2008; NICE, 2003
Treatment
An Educational Slide Set Developed by Professor Martin R Cowie National Heart and Lung Institute, Imperial College, LondonAims of treatment of chronic heart failure
The aims of therapy in heart failure are to: Improve life expectancy Improve quality of life The relative importance of these aims varies: Between patients Over timeTREATMENT
NICE, 2003
Modern management
The therapeutic approach in chronic heart failure due to systolic dysfunction consists of: Non-pharmacological measures Patient education Avoid obesity Dietary measures e.g. salt restriction if prescribed Avoid excessive fluid intake Smoking cessation Exercise/rehabilitation Influenza/pneumococcal vaccination Pharmacological therapy Devices and surgeryESC, 2008
TREATMENT
Co-morbidities that may impact on treatment (1)
Co-morbidityComments
COPD/asthma/reversible airways disease
Beta-blockers are contraindicated in patients with reversible airways disease
ACE inhibitors and angiotensin II receptor blockers may be contraindicated
NICE, 2003TREATMENT
Adapted from NICE 2003.
Co-morbidities that may impact on treatment (2)
Co-morbidityComments
Thyroid disease
Severe thyroid dysfunction may cause or precipitate heart failure
Peripheral vascular disease
High index of suspicion for renal artery stenosis required
Urinary frequency
Alpha blockers may cause hypotension or fluid retention but are not contraindicated; diuretics likely to be less well tolerated
Gout
Avoid NSAIDs; gout may be exacerbated by diuretics
NICE, 2003
TREATMENT
Adapted from NICE et al. 2003.
Treatment options for chronic heart failure Drug therapy
Diuretics Neurohormonal antagonists ACE inhibitors Beta blockers Aldosterone antagonists Angiotensin II receptor blockers Digoxin Other drugs Amiodarone Nitrates/Hydralazine Aspirin WarfarinTREATMENT
Diuretic therapy
Rapid relief of congestive symptoms and fluid retention, improving: Breathlessness Exercise performance May be titrated according to need following initiation of subsequent therapies No evidence for mortality benefit No effect on disease progression“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 initiation of subsequent heart failure therapies” NICE, 2003
TREATMENT
Use of oral diuretics
NICE, 2003Drug
Initial dose (mg)
Maximum recommended daily dose (mg)
Loop diuretics Bumetanide Furosemide Torasemide
0.5–1.020–405–10 5–10250–500100–200 Thiazides* Bendroflumethiazide (bendrofluazide) Indapamide Metolazone
2.5 2.5 2.5
5 2.5 10
Potassium-sparing diuretic Amiloride Triamterene
+ACEI –ACEI2.5 525 50 +ACEI –ACEI20 40100 200 *May be effective when added to loop diuretics when fluid retention is resistant, but can promote dramatic diuresis and disturbance in fluid balance and electrolytes. Patients must be closely monitored and specialist advice is required. ACEI=ACE inhibitor
TREATMENT
Adapted from NICE et al. 2003.
ACE inhibitor therapy for heart failure and LVSD
Systematic overview of data from five long-term RCTs Compared with placebo, ACE inhibitors reduce: Mortality (p<0.0001) Readmission (p<0.0001) Reinfarction (p<0.0001) Benefit begins early after the start of therapy and persists in the long-termFlather et al, Lancet; 2000
TREATMENT
5
Cumulative mortality (%)
40
30
20
10
0
0
1
2
3
4
Time since randomisation (years)
All trials
ACE-1 Placeb0
6391 6372
5378 5279
4204 4025
2457 2364
892 742
Adapted from Elather et al. 2000.
ACE inhibitor therapy for heart failure due to LVSD
“All patients with heart failure due to left ventricular systolic dysfunction should be considered for treatment with an ACE inhibitor.ACE inhibitor therapy should be instituted in patients with heart failure due to left ventricular systolic dysfunction before beta-blockade is introduced.”“ACE inhibitor therapy should be initiated at the appropriate dose, and titrated upwards at short intervals (eg every two weeks) until the optimal tolerated or target dose is achieved.” NICE, 2003TREATMENT
All patients with heart failure due to LVSD should be considered for treatment with an ACE inhibitor
NICE, 2003
Licensed ACE-I
Starting dose
Target dose
Captopril
6.25mg three times daily
50–100mg three times daily Cilazapril*
0.5mg once daily
1–2.5mg once daily Enalapril
2.5mg twice daily
10–20mg twice daily Fosinopril*
10mg once daily
40mg once daily
Lisinopril
2.5–5mg once daily 30–35mg once daily Perindopril*
2mg once daily
4mg once daily
Quinapril*
2.5–5mg once daily 10–20mg once daily Ramipril
2.5mg once daily
5mg twice daily or 10mg once daily
*Target dose based on manufacturer’s recommendation rather than large outcome study TREATMENT
Adapted from NICE et al. 2003.
Practical recommendations on use of ACE inhibitors (1) How to use
Start with a low dose Seek specialist advice where the patient is on a high dose (eg furosemide 80mg) of a loop diuretic Double dose at not less than two weekly intervals Aim for target dose or the highest tolerated dose Remember some ACE inhibitor is better than no ACE inhibitor Monitor blood electrolytes (in particular potassium), urea, creatinine and blood pressureNICE, 2003
If the patient develops a troublesome dry cough which interferes with sleep and is likely to be caused by an ACE inhibitor, consider substituting an angiotensin-II receptor blocker
TREATMENT
Practical recommendations on use of ACE inhibitors (2) Advice to patients
Explain expected benefits Treatment is given to improve symptoms, to prevent worsening of heart failure and to increase survival Symptoms improve within a few weeks to a few months Advise patients to report principal adverse effects, i.e. dizziness/symptomatic hypotension, cough.NICE, 2003
TREATMENT
If the patient develops a troublesome dry cough which interferes with sleep and is likely to be caused by an ACE inhibitor, consider substituting an angiotensin-II receptor blocker
* For non-inferiority p<0.025 denotes statistical significance (unilateral test)
Beta-blocker therapy for heart failure due to LVSD - Evidence published after NICE guidelineTREATMENT
% without Endpoint
months
Intention-to-treat (ITT)
50
60
70
80
90
100
0
6
12
18
B/E vs E/B HR 0.94 non-inferiority P=0.019*
505 505
389 388
291 277
87 76
Patients at risk
Bisoprolol-first
Enalapril-first
CIBIS III
Willenheimer et al, Circulation, 2005
Primary Objective: To show that initial monotherapy with bisoprolol for 6 months followed by combination therapy with enalapril was not inferior to the reverse order in preventing the combined endpoint of death and hospitalisation for all causes 1010 patients with NYHA class II or III and LVEF < 35% Mean follow-up of 1.25 years Very similar event rates with either approach but statistically the study just failed to demonstrate non-inferiority of bisoprolol-first approach
Adapted from Wilenheimer et al. 2005.
Beta-blocker therapy for heart failure due to LVSD
Pooled data from 25 RCTs (6511 patients and 810 deaths) Compared with placebo, beta-blockers reduced odds of death by 36% (95% CI 25% to 45%) No evidence of heterogeneity between trial results Benefit is additional to that of ACE inhibitorsCleland et al, BMJ, 1999
TREATMENT
Bisoprolol pooled (2 trials) Bucindolol pooled (4 trials) Carvedilol pooled (5 trials) Metoprolol pooled (9 trials) 5 small trials Overall (25 trials)
Fig 1 Pooled odds ratios (and 95% confidence intervals) describing the effect of beta blockers on mortality in patients with heart failure
Fig 2 Effect on annual rate of mortality (%) of angiotensin inhibitors alone, with beta blockers added, and with both drugs. Risk differences and 95% confidence intervals.
ACE inhibitors alone
Beta Blockers added
Combined effect
Absolute reduction in mortality in 1 year attributable to treatment (%)
0.1
0.2
0.5
1
2
5
10
-8
-6
-4
-2
0
Adapted from Cleland et al. 1999.
All patients with heart failure due to LVSD should be considered for treatment with a beta-blocker (1) Which beta-blocker and what dose?
Three beta-blockers are licensed for the treatment of heart failure in the UK: Bisoprolol (starting dose 1.25 mg once daily; target dose 10 mg once daily)Carvedilol (starting dose 3.125 mg twice daily; target dose 25–50 mg twice daily)Nebivolol (starting dose 1.25mg once daily; target dose 10mg once daily)NB Carvedilol: maximum dose 25 mg twice daily if severe heart failure. For patients with mild to moderate heart failure maximum dose 50 mg twice daily if weight more than 85 kg – otherwise maximum dose 25 mg twice daily NICE, 2003
TREATMENT
All patients with heart failure due to LVSD should be considered for treatment with a beta-blocker (2) How to use?
NICE, 2003
TREATMENT
Start with a low dose Double dose at not less than two weekly intervals Aim for target dose (see above) or, failing that, the highest tolerated dose Remember some beta-blocker is better than no beta-blocker Monitor heart rate, blood pressure, clinical status (symptoms, signs, especially signs of congestion and body weight) Check blood electrolytes, urea and creatinine one to two weeks after initiation and one to two weeks after final dose titration
When starting a patient on a beta-blocker (1) Ensure that the patient
TREATMENTUnderstands the expected benefits of beta-blockers: prevent worsening of heart failure improve symptoms (but may take 3-6 months or more) increase survival Knows that symptoms may deteriorate during initiation / up-titration phase Knows that beta-blockers should not be stopped without first seeking advice Understands that any deterioration (tiredness, fatigue, breathlessness) should be reported as this can be easily managed by adjusting other drugs Is encouraged to weigh themselves each day (after waking, before dressing, after voiding, before eating)
NICE, 2003
When starting a patient on a beta-blocker (2) If patients experience worsening symptoms/signs
TREATMENT
NICE, 2003
Congestion – double dose of diuretic or halve dose of beta-blockerFatigue – halve dose of beta-blocker (rarely necessary)Review patient in 1-2 weeks; if not improved seek specialist adviceSerious deterioration – halve beta-blocker dose or stop treatment and seek specialist advice
The Randomised Aldactone Evaluation Study (RALES)1663 patients with NYHA III or IV heart failure and ejection fraction ≤35% who were already treated with ACE inhibitor, diuretic ± digoxinSpironolactone 25mg od vs placebo, with patients followed for an average of 2 years30% reduction in the risk of death (p<0.001) and 35% reduction in risk of hospitalisation (p<0.001) among patients randomised to spironolactone Aldosterone antagonist therapy for heart failure due to LVSD
Pitt et al, N Engl J Med, 1999
TREATMENT
Probability of Survival
P < 0.001
RRR=0.30 (0.18-0.40)
Spironolactone
Placebo
Months
0
3
6
9
12
15
18
21
24
27
30
33
36
0.00
0.45
0.50
0.55
0.60
0.65
0.70
0.75
0.80
0.85
0.90
0.95
1.00
Adapted from Pitt et al. 1999.
NICE recommendation on spironolactone
Patients with heart failure due to LV systolic dysfunction who remain moderately to severely symptomatic despite optimal therapy should be prescribed spironolactone at a dose of 12.5 to 50 mg once per day – specialist advice should be soughtPatients with heart failure taking spironolactone should have blood potassium and creatinine levels monitored for signs of hyperkalaemia and/or deteriorating renal function. If hyperkalaemia is a problem then the dose of spironolactone should be halved and biochemistry rechecked Symptom improvement occurs within a few weeks to a few months of starting treatment Patients should avoid NSAIDs (including OTC products e.g. ibuprofen) Temporarily stop spironolactone if diarrhoea and/or vomiting and contact physician Male patients may develop breast discomfort and/or gynaecomastiaNICE, 2003
TREATMENT
3313 patients were randomised to eplerenone 25 mg/day and 3319 to placebo (in addition to ‘standard’ medical therapy).Mean follow-up of 16-months. Among those taking eplerenone there was:15% relative risk reduction in all-cause death (p=0.008)13% relative risk reduction in cardiovascular death or hospitalisation (p=0.002)21% relative risk reduction in sudden cardiac death ( p=0.03)Compared with spironolactone, eplerenone is less likely to cause gynaecomastia or breast tenderness, but K+ monitoring is still essential. Aldosterone antagonist therapy for heart failure after MI EPHESUS trial
Pitt et al, N Engl J Med, 2003
TREATMENT
36
No. at Risk Placebo Eplerenone
Cumulative Incidence (%)
Months since Randomization
p=0.008 RR=0.85
0
3
6
9
12
15
18
21
24
27
30
33
0
5
10
15
20
25
30
35
40
Placebo
Eplerenone
3313 3319
3064 3125
2983 3044
2830 2896
2418 2463
1801 1857
1213 1260
709 728
323 336
99 110
2 0
0 0
0 0
Adapted from Pit et al. 2003.
Digoxin
The oldest established treatment for heart failure Digoxin has a narrow therapeutic window Arrhythmias and gastrointestinal side effects are commonTREATMENT
How useful is digoxin? The DIG trial
6800 patients with heart failure (EF45%) already on diuretic + ACE inhibitor Randomised to digoxin or placebo, 250 g/day (mean dose) and followed for average of 37 monthsNo difference in total mortality (p=0.80)28% relative risk reduction in death or hospitalisation due to worsening HF (p<0.001) DIG, N Engl J Med, 1997TREATMENT
40
30
20
10
0
0
4
8
12
16
20
24
28
32
36
40
44
48
52
Placebo
Digoxin
p=0.80
Months
Mortality from Any Cause (%)
40
30
20
10
0
0
4
8
12
16
20
24
28
32
36
40
44
48
52
Placebo
Digoxin
P<0.001
Months
Death or Hospitalisation Due to Worsening Heart Failure (%)
Adapted from DIG 1997.
Adapted from DIG 1997.
NICE recommendation on digoxin
Digoxin is recommended for: worsening or severe heart failure due to LV systolic dysfunction despite ACE inhibitor, beta-blocker and diuretic therapy patients with atrial fibrillation and any degree of heart failureSeveral drugs can alter the pharmacokinetics of digoxin, especially: 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)
NICE, 2003
TREATMENT
Angiotensin II receptor blockers (ARBs)
Several ARBs have been tested for use in chronic heart failure due to LVSD:Losartan – ELITE and ELITE IIValsartan – Val-HeFT Candesartan – CHARMNICE stated“angiotensin-II receptor antagonists may provide an alternative to ACE inhibitors for patients intolerant of ACE inhibitors (for example, because of cough)”Since publication of the NICE guideline, new data are available on one agent – candesartan – which is also now licensed for use in patients with chronic heart failure and LVSD in the UK NICE, 2003; Pfeffer et al. Lancet 2003.TREATMENT
Angiotensinogen
Vasoconstriction Cell growth Na/H2O retention Sympathetic activationrenin
Angiotensin I
Angiotensin II
Angiotensin Converting Enzyme
ACE inhibitor side effects (cough, angioedema)
Bradykinin
Inactive Fragments
Vasodilation Antiproliferation
Aldosterone
AT2
AT1
Non-ACE pathways (e.g., chymase)
Why block the renin-angiotensin-aldosterone system at the AT1 receptor?
+
+
TREATMENT
Elite I
1.000.95
0.90
0.85
0.80
0.00
0
100
200
300
400
Losartan
Captopril
ARB outcome studies in chronic heart failure (1) - ELITE (losartan) studies
ELITE study (722 patients) found an unexpected 46% mortality reduction compared with captopril Findings not replicated in the ELITE II mortality trial (3152 patients) Losartan not shown to be superior to captopril for treatment of chronic heart failure
Pitt et al, Lancet, 1997; Pitt et al, Lancet, 2000
TREATMENT
Follow-up (days)
Probability of survival
1.0
0.8
0.6
0.4
0.2
0
Probability of survival
Losartan
Captopril
p=0.16
All-cause mortality
Elite II
p=0.0035
Adapted from Pitt et al. 1997 & 2000.
ELITE-1 Evaluation of Losartan in the Elderly
722 ACE inhibitor-naпve patients with heart failureEF 40% and age > 65 yearsLosartan vs captopril with 1 year follow-upPrimary end-point: persistent renal dysfunctionNo difference in primary end-point (10.5%)Losartan better tolerated than captoprilSurprise findings: Mortality reduced by 46%Death or hospitalisation reduced by 32%SCD reduced by 64%Pitt et al, Lancet 1997
TREATMENT
ELITE-2
3152 patients with CHF aged over 60 yearsNYHA II- IV and EF 40%Not treated with ACEI or AII receptor blocker in preceding 3 monthsLosartan 50mg od vs Captopril 50mg tds (both incremental)Primary endpoint: all-cause mortalityFollow-up for 3 years or until 406 deaths occurredNo significant difference between losartan and captopril for primary endpoint ၎ĜမĔࠀČČ иĀāĂ㥹h浤湡`ЉArial&Monotype TypographyĆćzྟྨ楐瑴攠⁴污慌据瑥〲〰ྡࠀྪࠉྦрǔːϰԐ̊ಢ氅ѓDǯЂАරїƿǿ̿쎀οTextBox 4ረ ьȰမȨࠀČČ иĀāĂ㥹h浤湡`ЉArial&Monotype TypographyĆćࠀČČ иĀāĂ㥹h浤湡`ЉArial&Monotype TypographyĆć^ྟྨ剔䅅䵔久ൔྡ$CྦрǔːϰԐH氆ఀѓ0ƁࠀƃࠀƓ龎‹Ɣ뷞hƿǿ̄̿ Pitt et al, Lancet, 2000TREATMENT
ELITE 2 Study Endpoint Summary
P Value
1.13 (0.95, 1.35)
P = 0.16 NS
1.25 (0.98, 1.60)
P = 0.08 NS
1.07 (0.97, 1.19)
P = 0.18 NS
228 ( 14.5 )
P <
0.001
149 ( 9.4 )
Losartan n = 1578 number ( % )
Captopril n = 1574 number ( % )
752 ( 47.7 )
707 ( 44.9 )
115 ( 7.3 )
142 ( 9.0 )
280 ( 17.7 )
250 ( 15.9 )
Hazards Ratio ( 95% CI )*
Withdrawal for Adverse Experiences
Combined total mortality or hospitalisations for any reason
Sudden death or/ resuscitated cardiac arrest
All-cause mortality (primary endpoint)
Pitt, B. et al, Lancet 2000; 355:1582-87
TREATMENT
Adapted from Pitt et al. 2000.
Hazard Ratio
AgeGender
NYHA Class.
% EF
Beta Blockers
Overall
70 70 Male
Female
III/IV
II
< 25
> 25
With
Without
1.05
1.33
1.12
1.14
1.19
1.37
1.00
1.19
1.77
1.05
1.13
Hazard
Ratio
3.0
1.0
0.8
0.6
2.0
Hazard Ratio of Death
with 95% C.I.
Subgroups at Baseline
Favors Losartan
Favors Captopril
ELITE 2 Mortality by Subgroup
913
661
1083
491
798
776
290
1284
325
1249
1574
N
Captopril
901
677
1102
476
801
777
267
1311
354
1224
1578
N
Losartan
Pitt, B. et al, Lancet 2000; 355:1582-87
TREATMENT
Adapted from Pitt et al. 2000.
ARB outcome studies in chronic heart failure (2) - Val-HeFT study
Valsartan or placebo added to ‘standard’ therapyVal-HeFT study found no difference in all-cause mortality (p=0.8)Valsartan arm showed a reduction in combined all-cause mortality & morbidity (RR 0.87; p=0.009)Post-hoc analysis suggested more deaths in those given combination of valsartan, ACE inhibitor and beta-blockerValsartan is not currently licensed in the UK for the management of chronic heart failure Cohn et al, N Engl J Med, 2001TREATMENT
100
95
90
85
80
75
70
0
0
3
6
9
12
15
18
21
24
27
Valsartan
Placebo
p=0.80
Months since Randomization
Probability of survival
Adapted from Cohn et al. 2001.
Val-HeFT Valsartan Heart Failure Trial
5010 patients with chronic stable HF (NYHA II-IV) & LVEF < 40% Valsartan or placebo added to standard therapy 1o end-point: all cause mortality (time to death) combined all-cause mortality & morbidity: All cause mortality Sudden death with resuscitation Hospitalisation for heart failure Need for therapeutic doses of IV inotropic or vasodilating agent for at least 4 hrs No significant difference in all cause mortality 13.2% RRR for valsartan in combined endpoint (P=0.009)Cohn et al, N Engl J Med, 2001
TREATMENT
1.0
0.9
0.8
0.7
Survival in Val-HeFT
Time since randomisation (months)
p = 0.80Survival probability (%)
0
3
6
9
12
21
18
15
24
27
Valsartan
Placebo
Cohn et al, N Engl J Med 2001
TREATMENT
Adapted from Cohn et al. 2001.
1.0
0.9
0.8
0.6
13.2% risk reduction p= 0.009
Val-HeFT combined mortality / morbidity endpoint
0
Event-free probability
Placebo
Valsartan
3
6
9
12
21
18
15
24
27
Time since randomisation (months)
0.7
Cohn et al, N Engl J Med 2001
TREATMENT
Adapted from Cohn et al. 2001.
Relative risks and 95% confidence intervals of primary endpoints according to background therapy at baseline
Cox regression model
Cohn et al, N Engl J Med, 2001
TREATMENT
Morbidity
ACEI + BB –
3,034
ACEI + BB +
1,610
ACEI – BB – 226
ACEI – BB + 140
Mortality
ACEI + BB –
3,034
ACEI + BB +
1,610
ACEI – BB – 226
ACEI – BB + 140
Favours valsartan
Favours placebo
0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0 1.1 1.2 1.3 1.4 1.5 1.6 1.7 1.8 1.9
Adapted from Cohn et al. 2001.
1.0
0.8
0.6
0.4
44.5% risk reduction p = 0.0002
Event-free probability
Time since randomisation (months)
3
6
9
12
21
18
15
24
27
0
Valsartan (n = 185)
Placebo (n = 181)
Subgroup analysis of combined mortality/morbidity greatest benefits in patients not on ACE inhibitor therapy
TREATMENT
Cohn et al, N Engl J Med, 2001
Adapted from Cohn et al. 2001.
The NICE treatment algorithm for chronic heart failure due to LVSD, 2003*
NICE, 2003TREATMENT
*Partial update to NICE guideline expected late 2010
Adapted from NICE et al. 2003.
Further Evidence and Guidance since NICE (2003)
An Educational Slide Set Developed by Professor Martin R Cowie National Heart and Lung Institute, Imperial College, LondonARBs in post-MI heart failure
TREATMENTOutcome studies in post-MI heart failure OPTIMAAL study
5477 patients with HF (and/or LVEF < 35%, and/or new anterior Q waves) after acute MI Randomised to losartan or captopril Primary end-point all-cause mortality Strong trend towards less benefit in those randomised to losartan (RR 1.13; p=0.07)Dickstein et al, Lancet, 2002
TREATMENT
Number at risk
Losartan Captoprill
2744 2733
2504 2534
2432 2463
2390 2423
2344 2374
2301 2329
1285 1309
Endpoint rate (%)
25
20
15
10
5
0
Losartan
Captoprill
Relative risk 1.13 p=0.069
0
6
12
18
24
30
36
Adapted from Dickstein et al. 2002.
Outcome studies in post-MI heart failure VALIANT study
Comparison of three arms: valsartan, valsartan and captopril, or captopril Patients with LVSD or heart failure after acute MI Primary endpoint all-cause mortality No difference in all-cause mortality between the three regimens (p=0.98) More drug-related adverse events in those given combination of captopril and valsartan Valsartan licensed in UK for treatment of HF and/or LVSD after acute MIPfeffer et al, NEJM, 2003
TREATMENT
Valsartan
Valsartan and captopril
Captopril
Probability of Event
0.4
0.3
0.2
0.1
0.0
0
6
12
18
24
30
36
Months
Adapted from Pfeffer et al. 2003.
CHARM Added
CHARM PreservedOutcome studies in chronic heart failure The CHARM Programme: 3 component trials comparing candesartan to placebo in patients with symptomatic heart failure
CHARM Alternative
n=2028 LVEF 40%ACE inhibitor intolerant n=3025 LVEF >40% ACE inhibitor treated/not treated
Primary outcome for each trial: CV death or CHF hospitalisation Primary outcome for overall programme: All-cause death
Pfeffer et al, Lancet 2003; Granger et al, Lancet, 2003; McMurray et al, Lancet, 2003; Yusuf et al, Lancet, 2003
TREATMENT
n=2548LVEF 40%ACE inhibitor treated
n=3025 LVEF >40% ACE inhibitor treated/not treated
CHARM PreservedCHARM Programme
3 component trials comparing candesartan to placebo
Primary outcome: CV death or CHF hosp
TREATMENTCHARM Alternative
n=2028 LVEF 40%ACE inhibitor intolerant CHARM Added
CHARM-Alternative: Primary outcome CV death or CHF hospitalisation
0
1
2
3
years
0
10
20
30
40
50
Placebo
Candesartan
%
HR 0.77 (95% CI 0.67-0.89), p=0.0004 Adjusted HR 0.70, p<0.0001
3.5
406 (40.0%)
334 (33.0%)
TREATMENT
Number at risk Candesartan Placebo
1013 1015
929 887
831 798
434 427
122 126
Granger et al, Lancet, 2003
Adapted from Granger et al. 2003.
CHARM-Alternative Permanent study drug discontinuations (all patients)
05
10
15
20
25
Percent of patients
Placebo
Candesartan
19.3
0.9
2.7
0.3
0.4
21.5
3.7
6.1
1.9
0.2
p=0.23
p<0.0001
p<0.0001
p=0.0005
p=0.69
Hypo- tension
Increased creatinine
Increased potassium
Cough
Adverse effects/ lab. abnorm.
0
0.1
p=0.50
Angio- edema
TREATMENT
Granger et al, Lancet, 2003
Adapted from Granger et al. 2003.
n=3025 LVEF >40% ACE inhibitor treated/not treated
CHARM AddedCHARM Preserved
CHARM Programme
3 component trials comparing candesartan to placebo
CHARM Alternative
Primary outcome: CV death or CHF hosp
TREATMENTCHARM-Added Baseline ACE inhibitor
ACE inhibitorProportion taking
Mean daily dose of ACE inhibitor (mg)
Candesartan
Placebo
enalapril
27%
17
17
lisinopril
19%
17
17
captopril
17%
82
83
ramipril
11%
7
7
TREATMENT
McMurray et al, Lancet 2003
Adapted from McMurray et al. 2003.
CHARM-Added: Primary outcome CV death or CHF hospitalisation
01
2
3
years
0
10
20
30
40
50
Placebo
Candesartan
3.5
HR 0.85 (95% CI 0.75-0.96), p=0.011 Adjusted HR 0.85, p=0.010
483 (37.9%)
538 (42.3%)
%
TREATMENT
Number at risk Candesartan Placebo
1276 1272
1176 1136
1063 1013
948 906
457 422
McMurray et al, Lancet 2003
Adapted from McMurray et al. 2003.
CHARM-Added Secondary outcomes
candesartan better
Hazard ratio
placebo better
0.6
0.8
1.0
1.2
1.4
p-value
0.029
0.014
0.010
0.020
0.015
Candesartan
Placebo
0.84
0.83
0.85
0.87
0.87
CV death
302
347
CHF hosp.
309
356
CV death, CHF hosp, MI
495
550
CV death, CHF hosp, MI, stroke
512
559
CV death, CHF hosp, MI, stroke, revasc.
548
596
TREATMENT
McMurray et al, Lancet, 2003
Adapted from McMurray et al. 2003.
CHARM-Added Prespecified subgroups, for CV death or CHF hospitalisation
CandesartanPlacebo
candesartan better
Hazard ratio
placebo better
0.6
0.8
1.0
1.2
1.4
p-value for treatment interaction
0.14
0.26
Beta-blocker
Yes No
223/702 260/574
274/711 264/561
Recom dose of ACE inhibitor
Yes No
232/643 251/633
275/648 263/624
All patients
483/1276
538/1272
TREATMENT
McMurray et al, Lancet, 2003
Adapted from McMuray et al. 2003.
CHARM-Added Permanent study drug discontinuations
PlaceboCandesartan
0
5
10
15
20
25
Percent of patients
p=0.0003
p=0.079
p=0.0001
p<0.0001
Hypo- tension
Increased creatinine
Increased potassium
Adverse effects/ lab. abnorm.
18.3
3.1
4.1
0.7
24.2
4.5
7.8
3.4
TREATMENT
McMurray et al, Lancet, 2003
Adapted from McMurray et al. 2003.
CHARM Programme
n=3025 LVEF >40% ACE inhibitor treated/not treatedCHARM Added
CHARM Preserved
3 component trials comparing candesartan to placebo
CHARM Alternative
Primary outcome: CV death or CHF hosp
TREATMENTBaseline characteristics
Alternative n=2028Added n=2548
Preserved n=3023
Overall n=7599
Mean age (years)
67
64
67
66
Women (%)
32
21
40
32
NYHA class (%) II III IV
48 49 3
24 73 3
60 38 2
45 52 3
Mean LVEF
30
28
54
39
Medical history (%) myocardial infarction diabetes hypertension atrial fibrillation
61 27 50 25
56 30 48 26
44 28 64 29
53 28 55 27
TREATMENT
CHARM-Preserved: Primary outcome CV death or CHF hospitalisation
01
2
3
years
3.5
0
10
20
30
Placebo
Candesartan
5
15
25
HR 0.89 (95% CI 0.77-1.03), p=0.118 Adjusted HR 0.86, p=0.051
%
366 (24.3%)
333 (22.0%)
TREATMENT
Number at risk Candesartan Placebo
1514 1509
1458 1441
1377 1359
833 824
182 195
Yusuf et al, Lancet, 2003
Adapted from Yusuf et al. 2003.
CHARM-Preserved Investigator reported CHF hospitalisations
PlaceboCandesartan
p=0.014
p=0.017
Patients hospitalised
Hospitalisations
Proportion of patients (%)
Number of episodes
Yusuf et al, Lancet, 2003
TREATMENT
Adapted from Yusuf et al. 2003.
Adapted from Yusuf et al. 2003.
CHARM Programme Mortality and morbidity
0.70.8
0.9
1.0
1.1
1.2
0.6
0.7
0.8
0.9
1.0
1.1
1.2
All Cause Mortality
CV Death or CHF Hospitalisation
Hazard ratio
Hazard ratio
heterogeneity p=0.43
Alternative
Added
Preserved
Overall
heterogeneity p=0.37
p=0.0004
p=0.055
p=0.011
p=0.118
p<0.0001
0.77
0.85
0.89
0.84
0.91
TREATMENT
Rates of all cause mortality in the combined low ejection fraction CHARM trials
Young et al, Circulation, 2004TREATMENT
All-cause death (%)
Placebo
Hazard ratio 0.88 (95% Cl 0.79 - 0.98), p=0.018
Candesartan
40
35
30
25
20
15
10
5
0
0
1
2
3
3.5
yrs
Number at risk
Candesartan Placebo
2289 2287
2105 2023
1894 1811
1382 1333
580 548
Adapted from Young et al. 2004.
Which ARB and what dose?
Three ARBs (candesartan, losartan and valsartan) are now licensed for the treatment of chronic heart failure in the UK.TREATMENT
ARB
Dose range
ACE-I intolerant alternative
ACE-I Add on
Beta blocker warning
Candesartan
Starting: 4mg od Target: 32mg od
Yes
Yes
No
Losartan
Starting: 12.5mg od Target: 50mg od
Yes*
No
* Caution when used together with a beta blocker
Valsartan
Starting: 40mg bd Target: 160mg bd
Yes
Yes#
# Only recommended as add-on when beta blockers not tolerated
Major trials of HF with preserved EF (‘HFPEF’) Three major trials have assessed treatment of HFPEF CHARM PRESERVED (candesartan) PEP-CHF (perindopril) I-PRESERVE (irbesartan)
TREATMENT
PEP-CHF study Time to death or unplanned HF hospitalisation (primary endpoint)
TREATMENTCleland et al, Eur Heart J, 2006
Adapted from Cleland et al. 2006.
Irbesartan for HFPEF I-PRESERVE trial
Hypothesis:Irbesartan will reduce mortality and morbidity in patients with HFPEFDesign:Double-blind, placebo-controlled trial of irbesartan 300mg od in 4128 patients involving 360 centres in 29 countriesEntry criteria:Aged ≥ 60 years, symptomatic CHF with EF ≥ 45% with recent HF hospitalisation or other finding consistent with diastolic dysfunction, with or without ACE inhibitor background (limited to 1/3)Primary endpoint:All cause mortality and cardiovascular hospitalisations TREATMENTCarson et al, J Card Fail, 2005; Massie et al, NEJM, 2008
I-PRESERVE All cause mortality + CV hospitalisation
Massie et al, NEJM, 2008TREATMENT
Adapted from Massie et al. 2008.
HR = 0.95 [0.86-1.05] P=0.35
I-PRESERVE All cause mortality + CV hospitalisation: subgroup analysis
Massie et al, N Engl J Med, 2008
TREATMENT
Adapted from Massie et al. 2008.
I-PRESERVE Secondary outcomes
Adapted from Massie et al, NEJM, 2008TREATMENT
Outcomes
Placebo (n=2061)
Irbesartan (n=2067)
Hazard ratio (95% CI)
P value
No. Patients with event
Event rate per 1000 patient years
No. Patients with event
Event rate per 1000 patient years
Death from any cause
436
52.3
445
52.6
1.00 (0.88-1.14)
0.98
Death from heart failure or hospitalisation for heart failure #
438
57.4
428
54.8
0.96 (0.84-1.09)
0.51
Myocardial infarction, stroke or death from a cardiovascular cause
400
49.4
402
48.9
0.99 (0.86-1.13)
0.84
Death from a cardiovascular cause or non fatal myocardial infarction or stroke
302
36.3
311
36.7
1.01 (0.86-1.18)
0.92
Hospitalisation for a protocol specified cardiovascular cause
537
74.3
521
70.6
0.95 (0.85-1.08)
0.44
Hospitalisation for worsening heart failure
336
44.0
325
41.6
0.95 (0.81-1.10)
0.5
Hospitalisation for any cause
1126
199.8
1152
203.6
1.02 (0.94-1.11)
0.64
# Death from heart failure includes death due to pump failure and sudden death
Ongoing StudiesHEAAL studyMedium versus high dose losartan in ‘low EF’ HF 3834 patients with chronic stable heart failure (NYHA II-IV) and LVEF ≤ 40%Intolerant of ACE inhibitorLosartan 50mg (‘antihypertensive dose’) vs 150mg (‘high dose’) once daily added to standard therapy Primary end-point: all cause mortality and heart failure hospitalisation Event-driven trial: results expected 2009 Konstam et al, Eur J Heart Failure 2008
TREATMENT
ESC Guideline (2008 update)recommendations on ARBs For patients with LVSD (EF ≤ 40%) ARBs are a good alternative to ACE inhibitors in symptomatic patients intolerant to ACE inhibitors (Level of evidence B; Recommendation Class 1) After acute MI with signs of HF or LVSD, ARBs have similar efficacy to ACE inhibitors (Level of evidence B; Recommendation Class 1) ARBs are recommended in combination with optimal ACE inhibitor + beta blocker in patients who remain symptomatic, unless taking an aldosterone antagonist (Level of evidence A; Recommendation class 1)
ESC, 2008
TREATMENT
ESC treatment algorithm for patients with symptomatic heart failure and reduced EF
Adapted from ESC Guidelines, 2008TREATMENT
Clinical implications
Both ACEI and ARB antagonise the RAA systemARBs are generally better tolerated than ACE inhibitorsARBs increasingly being used for ACE intolerant patients with ‘low EF’ heart failure or LVSD (whether CHF or post-MI) Also evidence for candesartan as ‘add on’ to other standard CHF therapies of ACEI + -blocker in CHF Use the drug and dose proven in RCTsNon-systolic (‘normal EF’) heart failure data less compelling — in general, physicians treat co-morbidity and fluid retention TREATMENTSIGN guideline recommendations on ARBs
Patients with chronic heart failure due to LVSD alone, or heart failure, LVSD or both following MI who are intolerant of ACE inhibitors should be considered for an ARB Patients with heart failure due to LVSD who are still symptomatic despite therapy with an ACE inhibitor and a beta-blocker may benefit from the addition of candesartan, following specialist adviceSIGN, 2007
TREATMENT
Additional Treatment Options
An Educational Slide Set Developed by Professor Martin R Cowie National Heart and Lung Institute, Imperial College, LondonOther medical treatments (1)
Anticoagulants“Anticoagulation is indicated for patients with the combination of heart failure and atrial fibrillation.”“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.” Amiodarone“The decision to prescribe amiodarone should be made in consultation with a specialist. The need to continue the prescription should be reviewed regularly.”“Patients taking amiodarone should have a routine six-monthly clinical review, including liver and thyroid function tests, including a review of side effects.” NICE, 2003TREATMENT
Aspirin“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).”Calcium channel blockers‘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” NICE, 2003
TREATMENT
Other medical treatments (2)
Other medical treatments (3)
Isosorbide/hydralazine combination“An isosorbide/hydralazine combination may be used in patients with heart failure who are intolerant of ACE inhibitors or angiotensin-II receptor antagonists.” Inotropic agents“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.” NICE, 2003TREATMENT
Statins in chronic heart failure
Two randomised controlled trials — CORONA and GISSI-HF — have shown no mortality benefit of statin therapy in patients with chronic heart failure, irrespective of its aetiology Kjekshus et al, N Engl J Med 2007; GISSI-HF investigators, Lancet 2008Other treatment options Surgery and devices
Coronary revascularisation (PCI/CABG) Transplantation Left ventricular assist device (LVAD) Cardiac resynchronisation therapy (CRT) Implantable cardioverter defibrillator (ICD) Other invasive therapies Valve repair/replacement Left ventricular aneurysmectomyNICE, 2003
TREATMENT
Treatment options for chronic heart failure Revascularisation
PCI/CABG may relieve ischaemic symptoms and improve mortality in heart failure patients with multi-vessel disease and stable anginaRCTs are currently examining whether patients with CHF, no angina, but ‘hibernating’ myocardium may benefit from revascularisation “Coronary revascularisation should not be routinely considered in patients with heart failure due to systolic left ventricular impairment unless they have refractory angina” NICE, 2003Picture courtesy of Dr V Naidoo, Royal Brompton Hospital.
TREATMENT
Treatment options for chronic heart failure Transplantation
Limited availability of donor organs Prioritisation for patients with severe symptoms and limited co-morbidity Few UK centres Chronic immunotherapy required 5 year survival 70-80%“Specialist referral for transplantation should be considered in patients with severe refractory symptoms or refractory cardiogenic shock” NICE, 2003
Picture courtesy of Dr M Sheppard, Royal Brompton Hospital
TREATMENT
Most often used as a “bridge” to transplantation for patients with end-stage heart failureModern devices are implantableMay be complicated by infection and thromboembolismSmall studies suggest long-term use in non-transplant candidates (“destination therapy”) may improve length and quality of life. Further studies ongoing. Rose et al, N Engl J Med, 2001; NICE, 2003
Picture courtesy of Prof. J Pepper, Royal Brompton Hospital.
TREATMENT
100
80
60
40
20
0
0
6
12
18
24
30
100
80
60
40
20
0
0
6
12
18
24
30
LV assist device
Medical therapy
Months
Survival (%)
Treatment options for chronic heart failure Ventricular assist device (VAD)
Cardiac resynchronisation therapy (CRT) NICE Technology Appraisal (No 120) – May 2007 CRT-P is an option for patients who:Have NYHA class III-IV symptomsAre in sinus rhythm either with QRS duration ≥150ms estimated by ECG or with QRS 120-149ms and mechanical dyssynchrony on echocardiographyHave LVEF ≤35% Are receiving optimal pharmacological therapyCRT-D is an option for patients who:Also fulfil criteria for an ICD TREATMENT
Picture courtesy of Medtronic
NICE, 2007
CRT for chronic heart failure COMPANION study (1)
1520 patients (NYHA III-IV despite optimal medical therapy) with QRS>120ms Randomised to continued best medical therapy alone or CRT with or without an implantable defibrillator (D) Primary endpoint: death from, or hospitalisation for, any cause CRT alone (HR 0.81; p=0.014) CRT+D (HR 0.80; p=0.01)Bristow et al, N Engl J Med, 2004
TREATMENT
100
80
60
40
20
0
0
120
240
360
480
600
720
840
960
1080
Event-free Survival (%)
Days after Randomization
Pacemaker (414 events, p=0.014)
Pacemaker- defibrillator (390 events, p=0.010)
Pharmacologic therapy (216 events)
Secondary endpoint: death from, or hospitalisation for, heart failure CRT alone (HR 0.75; p=0.002) CRT+D (HR 0.72; p=<0.001) Secondary endpoint: total mortality CRT alone (HR 0.76; p=0.059) CRT+D (HR 0.64; p=<0.003)
Bristow et al, N Engl J Med, 2004
TREATMENT
100
80
60
40
20
0
0
120
240
360
480
600
720
840
960
1080
Event-free Survival (%)
Days after Randomization
Pacemaker (237 events, p=0.002)
Pacemaker-defibrillator (212 events, P<0.001)
Pharmacologic Therapy (145 events)
CRT for chronic heart failure COMPANION study (2)
CRT for chronic heart failure Cardiac Resynchronisation – Heart Failure (CARE-HF) study 813 patients (NYHA III-IV due to LVSD and cardiac dysynchrony receiving standard medical therapy) Randomised to continued medical therapy with or without cardiac resynchronisation 37% reduction in primary endpoint (death or unplanned hospitalisation for cardiovascular event) (p<0.001) 36% reduction in secondary endpoint (death from any cause) (p=0.002)
Cleland et al, N Engl J Med, 2005
TREATMENT
1500
100
75
50
25
0
0
500
1000
Days
Medical therapy
Cardiac resynchronization
P<0.001
Percentage of Patients Free of Death From Any Causes or Unplanned Hospitalisation for a Major Cardiovascular Event
Implantable cardioverter-defibrillators (ICDs) NICE Technology Appraisal (No 95) – Jan 2006 ICDs Secondary Prevention
Cardiac arrest due to VT or VF Spontaneous sustained VT causing syncope or significant haemodynamic compromise Sustained VT without syncope/cardiac arrest and EF < 35% but no worse than NYHA Class III HF
NICE HTA, 2006
TREATMENT
Implantable cardioverter-defibrillators (ICDs) NICE Technology Appraisal (No 95) – Jan 2006 ICDs Primary Prevention
History of previous MI (>4 weeks) and all three of the following:Non-sustained VT on Holter monitoringInducible VT on EP testingLVSD (EF < 35%) and no worse than NYHA Class III HFHistory of previous MI (>4 weeks) and:LVSD (EF < 30%) and no worse than NYHA Class III HF and QRS duration of equal to or more than 120 millisecondsFamilial cardiac condition with a high risk of sudden death including Long QT, HCM, Brugada, ARVD, repair of Fallot’s NICE HTA, 2006
TREATMENT
Implantable cardioverter-defibrillators (ICDs) SCD-HeFT study
ICD n=829Amiodarone n=845
Placebo n=847
5 years all-cause mortality
182 (22%)
240 (28%)
244 (29%)
Hazard ratio vs placebo
0.77 (p=0.007)
1.06 (p=0.53)
Bardy G et al, N Engl J Med, 2005
Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT)1676 patients (NYHA class II-III/LVEF ≤35%) on optimal ‘medical’ therapyRandomised to amiodarone vs placebo vs ICD (single chamber) in addition to conventional therapyMedian follow-up 45 months TREATMENT
Chronic disease management
An Educational Slide Set Developed by Professor Martin R Cowie National Heart and Lung Institute, Imperial College, London
Treatment monitoring checklist (1) Follow-up interval should be a maximum of six months
CHRONIC DISEASE MANAGEMENTNICE, 2003
Assessment of functional capacity History/change in NYHA class/quality of life questionnaires/6-minute corridor walk test or cardiopulmonary exercise test Assessment of fluid status Changes in body weight/lying and standing blood pressure/jugular venous distension/lung crackles/hepatomegaly/ extent of peripheral oedema Assessment of cardiac rhythm Physical examination and/or 12-lead ECG, or 24-hour ECG monitoring if paroxysmal arrhythmia is suspected Laboratory assessment As minimum: serum biochemistry (urea, electrolytes, creatinine)/ thyroid function tests if on amiodarone/liver function tests if on amiodarone/coagulation control if on warfarin
Treatment monitoring checklist (2) Follow-up interval should be a maximum of six months
CHRONIC DISEASE MANAGEMENTNICE, 2003
Management plan Is the patient following advice on diet/physical activity/exercise? Co-medications Check current medication (both prescribed and over-the- counter (OTC)) Medical complications Consider angina or other symptoms of coronary artery disease/deep vein thrombosis/depression/renal dysfunction/anaemia
Patient self-monitoring
Patients can monitor their volume status by daily weighing and appropriate adjustment of their diuretic regimenRequires education and supportPatients should be taught how to recognise early signs of decompensation and how to seek professional helpHeart failure nurse usually most appropriate professional to ‘train’ patient NICE, 2003CHRONIC DISEASE MANAGEMENT
Remote monitoring
Remote monitoring of patients’ clinical status (telemonitoring) can improve access to health careFacilitates earlier detection of deteriorationAcceptable and easy to use by patientsLikely to become part of a modern heart failure management programme CHRONIC DISEASE MANAGEMENT
Typical equipment for telemonitoring
Riley, Heart, 2009
Side-effects of drugs commonly used in the treatment of heart failure (1)
NICE, 2003CHRONIC DISEASE MANAGEMENT
Diuretics Common: postural hypotension, gout, urinary urgency Serious: electrolyte imbalance (hypokalaemia, hypomagnesia, hyponatraemia), arrhythmia ACE inhibitors Common: cough, hypotension including postural Serious: worsening renal function, renal infarction in renal artery stenosis, angio-oedema Beta-blockers Common: tiredness, bradycardia, coldness Serious: asthmatic attack, exacerbation of heart failure, heart block Spironolactone Common: gynaecomastia, tiredness, rashes; Serious: hyperkalaemia, hyponatraemia
Side-effects of drugs commonly used in the treatment of heart failure (2)
NICE, 2003CHRONIC DISEASE MANAGEMENT
Digoxin Common: nausea Serious: life threatening arrhythmias Angiotensin II receptor blockers Common: hypotension including postural Serious: worsening renal function, renal infarction in renal artery stenosis Amiodarone Common: photosensitivity, nausea, thyroid dysfunction, sleep disturbance, corneal microdeposits Serious: thyrotoxic storm, pro-arrhythmia, pulmonary/hepatic fibrosis
Improving adherence to drug therapy
Non-adherence with treatment is associated with a high risk of readmission to hospital Non-adherence may be reduced by: Simplifying drug dosing regimens Educating patients/carers about medicines, and the reasons for taking themNICE recommendation: 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
NICE, 2003 & 2009
CHRONIC DISEASE MANAGEMENT
Drugs to avoid or use with caution (1)
Some analgesicsNon-steroidal anti-inflammatory drugs (NSAIDs) including OTC drugs such as aspirin or ibuprofen (often in ‘flu and cold remedies) COX-2 inhibitorsClass I anti-arrhythmicsCalcium-channel blockersRate limiting non-dihydropyridine CCBs verapamil and diltiazemFirst generation dihydropyridine derivatives such as nifedipineAmlodipine and felodipine are relatively safe to use NICE, 2003CHRONIC DISEASE MANAGEMENT
Drugs to avoid or use with caution (2)
Tricyclic antidepressantsImipramine, amitriptyline, clomipramine, dothiepin, lofepramine or nortriptylineParenteral corticosteroidsPrednisoloneLithiumSt John’s wort (hypericum perforatum) (OTC herbal remedy, with widely different activity in different preparations, interacts with warfarin, digoxin & other drugs) NICE, 2003CHRONIC DISEASE MANAGEMENT
End of life issues
Palliative care aims to improve the quality of life for terminally ill patients and to help family and carers by: Providing symptom control Providing psychological and social support Planning for the future and providing end of life care Specialist palliative care in cancer: Improves symptom control Reduces time spent in hospital Improves patient and carer choice and satisfaction Reduces overall costs Anecdotal evidence suggests benefit in heart failure Providing palliative care is complexNICE, 2003
CHRONIC DISEASE MANAGEMENT
“The palliative needs of patients and carers shouldbe identified, assessed and managed at the earliest opportunity.”“Patients with heart failure and their carers should have access to professionals with palliative care skills within the heart failure team.” NICE, 2003
CHRONIC DISEASE MANAGEMENT
NICE recommendations
New initiatives in end of life care
First national End of Life Care strategy‘Better Together’ palliative care service for heart failure patients set up by British Heart Foundation and Marie Curie Cancer CareLiverpool Care Pathway for the Dying (LCP) has been adapted for use with heart failure patients CHRONIC DISEASE MANAGEMENTDepression: common and important
Consider depression in all patients with heart failure Studies suggest a prevalence of depression of around 30% in non-hospitalised patients with heart failure Diagnosis is more common in those with physical symptoms and poorer physical functioning Depressive symptoms are strongly linked with a worse outcomeRumsfeld et al, 2003; Friedman et al 2001, Jiang et al, 2004
CHRONIC DISEASE MANAGEMENT
“Where depression is likely to have been precipitated by heart failure symptoms, reassess psychological status once the physical condition has stabilised following treatment for heart failure. If the symptoms have improved no further specific treatment for depression is required.”“Where depression co-exists with heart failure, patients should be treated for depression following existing NICE guidance.”“The risk/benefit of drug therapies for depression should be considered carefully in patients with heart failure. Antidepressants may lead to fluid retention, hypotension, or arrhythmia.”“Consider the potential for interaction with prescribed and OTC medications (including herbal products such as St John’s Wort, which reduces the efficacy of digoxin and warfarin)” NICE recommendations
NICE, 2003
CHRONIC DISEASE MANAGEMENT
Communication is essential for good discharge planning
Patients with heart failure should generally be discharged from hospital only when their clinical condition is stable and their management plan is optimised The timing of discharge should take into account both patient and carer wishes and the level of care and support that can be provided in the community The primary care team, patient and carer must be aware of the management plan Clear instructions should be given as to how the patient/carer can access advice particularly in the high risk period immediately following dischargeNICE, 2003
CHRONIC DISEASE MANAGEMENT
Best practice in communication
Listen to patients and respect their views and beliefsGive patients information about their condition, its treatment and prognosis, in a way they can understandProvide the most important information firstExplain how each item will affect patients personallyPresent information in separate categoriesMake advice specific, detailed and concreteUse words the patients will understandRepeat the information using the same words each timePrepare material, written or taped, to back up handwritten notesShare information with patients’ partners, close relatives or carers if they ask you to do so NICE, 2003CHRONIC DISEASE MANAGEMENT
Before discharge, patients need to understand
Why they need to follow a balanced diet That reducing sodium in their diet and limiting fluid intake will avoid counteracting the benefits of diuretic therapy Why they need to monitor their weight each day to guard against fluid retention That they should carry a list of all current medications, dosages and dosing frequencies What side-effects they might experience and how to manage them What they can expect with regard to energy and activity levels Any specific follow-up visit instructionsCHRONIC DISEASE MANAGEMENT
Rehabilitation programmes
Small trials suggest benefit in patients with heart failure Programmes should aim to combine exercise, psychological support and education Largest study to date of exercise training, HF-ACTION, randomised 2331 patients to an exercise training programme or usual care: no difference in all-cause hospitalisation or death (primary end point) secondary analysis (adjusting for baseline differences in prognostic variables) suggested benefit, with 11% reduction in primary endpoint and 15% reduction in cardiovascular mortality and heart failure hospitalisation (both p=0.03) exercise training was safeNICE, 2003; AHA, 2008
CHRONIC DISEASE MANAGEMENT
“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” CHRONIC DISEASE MANAGEMENT
NICE, 2003
NICE recommends
Circumstances in which referral to a“specialist” may be required Heart failure due to valve disease, diastolic dysfunction or any other cause except LV systolic dysfunction Severe heart failure (NYHA Class III/IV) Heart failure that does not respond to treatment as discussed in the NICE guideline When there are significant co-morbidities Angina, atrial fibrillation or other symptomatic arrhythmia Women who are planning a pregnancy or who are pregnant Heart failure that can no longer be managed effectively in the home setting
NICE, 2003
CHRONIC DISEASE MANAGEMENT
Who is a specialist in heart failure?
The NICE guideline recognises that the term specialist is applicable to a wide range of healthcare professionalsA heart failure specialist is defined as “a healthcare professional with special knowledge and experience in heart failure”Heart failure specialists may include:Cardiologist or other physicianGeneral practitioner or a specialist nurse with appropriate special knowledge and experience in heart failureIn addition, a number of other healthcare professionals will play an important role in the care of patients with heart failure (e.g. pharmacist, health psychologist, physiotherapist, dietician, district nurse) NICE, 2003CHRONIC DISEASE MANAGEMENT
Models of care
An Educational Slide Set Developed by Professor Martin R Cowie National Heart and Lung Institute, Imperial College, LondonIntegrated Heart Failure Service HF cardiologist HF specialist nurses Geriatrician/pharmacist/GPwSI and others
General medical clinics
General cardiology clinics
Primary Care
Open access echo
Primary Care
Primary Care + specialist nurse
Diagnosis Planning of management (Periodic review)
MODELS OF CARE
How should heart failure services be configured? British Society for Heart Failure Recommendations, 2004
Advanced heart failure service
McDonagh, Heart, 2005
Post MI patients
Inpatient decompensated CHF
Adapted from McDonagh et al. 2005.
Rich et al, NEJM, 1995; NICE, 2003
HF patients >70 years at high risk of readmission Usual care compared with an intervention comprising education, dietary advice, cardiology review, home visits and telephone contact Relative risk of readmission was reduced by 44% during a 3 month period after dischargeNICE recommends“Heart failure care should be delivered by a multidisciplinary team with an integrated approach across the healthcare community.” Nurse-led care is beneficial US study
MODELS OF CARE
1.00
0.80
0.60
0.40
0.20
0.00
0
10
20
30
40
50
60
70
80
90
p=0.035
Control
Treatment
Days after Initial Hospital Discharge
Probability of Not Being Readmitted
Adapted from Rich et al. 2003.
Nurse-led care is beneficial Glasgow study
Compared with usual care, nurse-led care: Reduced all cause admissions (86 vs 114, p=0.018) Reduced heart failure admissions (19 vs 45, p<0.001) Reduced days in hospital (3.43 vs 7.46, p=0.005)Blue et al, BMJ, 2001
MODELS OF CARE
100
90
80
70
60
50
40
30
20
10
0
0
2
4
6
8
10
12
Intervention
Usual care
p=0.033
No of months since randomisation
% event free survival
Nos at risk: Usual care Intervention
81 84
57 74
50 60
42 49
35 44
27 34
22 28
Adapted from Blue et al. 2001.
Recent trial evidence COACH study
Basic or intensive support by heart failure specialist nurse compared with control group (cardiologist follow up) No significant difference in primary endpoint of death or rehospitalisation for heart failure Suggests that if background care is good, there may be little extra benefit to be gained from nurse-led disease management programmesMODELS OF CARE
Duration of follow-up (months)
Jaarsma et al, Arch Intern Med, 2008
Adapted from Jaarsma et al. 2008.
Role of the specialist heart failure nurse (1)
Nurses often work within multi-disciplinary teams across the patient care pathway, from community settings to the acute sector, to ensure comprehensive services for heart failure patients: Heart failure clinics, whether hospital or community based Heart failure rehabilitation classes (advice on exercise and lifestyle) Support Groups where patients and carers can meet informally to support and learn from each otherMODELS OF CARE
Role of the specialist heart failure nurse (2)
Nurses may visit patients and their carers:Monitoring the patient’s status and medicationsAdvising on lifestyle changes (particularly related to diet and exercise)Providing emotional supportNurses may be involved in training practice nurses and health visitors MODELS OF CARELiaison between primary, secondary and tertiary careImplementation of NSF and GMS contractLocality heart failure register and auditAcademic detailing and education of colleagues within the PCTContinuing training/CPDService developmentPrimary care research capacity/pragmatic research projects Likely to be a ‘local champion’ for heart failure services GPs with special interest in cardiology
MODELS OF CARE
Non-medical prescribing
Nurses and pharmacists who have had suitable training can prescribe medicines as either:Independent prescribers — can prescribe any licensed medicine for any medical condition within their level of experience and competence (except CDs*)Supplementary prescribers — can prescribe any medicine, including CDs and unlicensed medicines, for any medical condition under the terms of a written management plan*Nurses can prescribe some controlled drugs (CDs). Pharmacists cannot currently prescribe CDs. MODELS OF CAREIndependent prescribing by a nurse or pharmacist
Nurse and pharmacist independent prescribing can help GP practices and hospital and primary care trusts to: Fill geographical or skills gaps in services Meet needs of patients who find it hard to access services, eg, the housebound, people with busy lifestyles Manage long-term conditions Manage co-morbidities/complex medication regimes This system is appropriate where the nurse or pharmacist works remotely from a doctor, seeing patients independentlyDepartment of Health, 2006
MODELS OF CARE
Supplementary prescribing is “a voluntary prescribing partnership between an independent prescriber (doctor) and a supplementary prescriber to implement an agreed patient-specific clinical management plan (CMP), with the patient’s agreement”No specific formulary for supplementary prescribers (SPs). All medicines in the CMP can be prescribedThe plan can cover dose-titration and add-on therapies in order to achieve set targetsSupplementary prescribing is most useful for patients with long-term conditions who can be managed by the SP between reviews by a doctor Department of Health, 2006
MODELS OF CARE
Independent prescribing by a nurse or pharmacist
The supplementary prescribing clinical management plan
Patient-specific document drawn up by both ‘independent’and ‘supplementary’ prescriberFor a patient with heart failure, the CMP should address:Lifestyle factors, such as diet and physical activityPreferred order and dosage range of:DiureticsACE-inhibitorsAngiotensin receptor blockersBeta-blockersWarnings about known sensitivities to drugsArrangements for notification of adverse drug reactionsWhen to refer back to the independent prescriberDate of review of CMP MODELS OF CAREUseful addresses
British Heart FoundationGreater London House, 180 Hampstead Road, London NW1 7AWTel: 020 7554 0000; Heart Information Line 0300 330 3311www.bhf.org.uk British Society for Heart Failure‘Nought’ The Farthings, Marcham, Oxfordshire OX13 6QDTel: 01865 391836E-mail: info@bsh.org.ukwww.bsh.org.ukNHS Heart Improvement Programme (part of NHS Improvement)www.heart.nhs.uk/heart National Institute for Health and Clinical ExcellenceMidCity Place, 71 High Holborn, London WC1V 6NATel: 020 7067 5800E-mail: nice@nice.org.ukwww.nice.org.ukThe Royal College of Physicians11 St Andrew’s Place, Regent’s Park, London NW1 4LETel: 020 7935 1174www.rcplondon.ac.ukDeveloped by Professor Martin R Cowie National Heart and Lung Institute, Imperial College, London