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© The European Society of Cardiology 2005. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org

Epidemiology, treatment, and guidelines for the treatment of heart failure in Europe

Michal Tendera*

Third Department of Cardiology, Silesian School of Medicine, Ziolowa Street 47, 40-635 Katowice, Poland

* Corresponding author. Tel: +48 32 353 9543; fax: +48 32 252 3930. E-mail address: mtendera{at}kardio3.katowice.pl


   Abstract
Top
 Abstract
Introduction
 Epidemiology of CHF
 Pharmacological treatment and...
 Summary
 Acknowledgements
 References
 
Chronic heart failure (CHF) is associated with a heavy burden of disease for patients and healthcare professionals. Quality of life and long-term prognosis for affected patients remain poor, and 5-year survival has been likened to that associated with some of the major malignancies. As a result of the ageing of the global population and the availability of effective treatments to prolong survival in patients with acute coronary syndromes, the incidence of CHF is increasing and the number of patients at risk of developing this condition is expected to grow. Despite the increasing prevalence of heart failure (HF), particularly in elderly populations, its exact incidence and prevalence remain largely unknown and probably underestimated due to a lack of accurate epidemiological data and difficulties associated with correct diagnosis. As a result, HF is associated with widespread undertreatment and the allocation of appropriate resources remains problematic. Numerous pharmacological therapies are available for the effective management of CHF, supported by a wealth of data from large scale, randomized clinical trials. Widespread adoption and implementation of evidence-based guidelines and treatment strategies are vital if survival is to be improved and patients are to receive optimal care for this devastating condition.

Key Words: Chronic heart failure • Epidemiology • Treatment • Europe


   Introduction
Top
 Abstract
 Introduction
Epidemiology of CHF
 Pharmacological treatment and...
 Summary
 Acknowledgements
 References
 
Chronic heart failure (CHF) develops as a result of left ventricular (LV) systolic and/or diastolic dysfunction.1 It is the only major cardiovascular disease whose prevalence and incidence are thought to be increasing,2 and it has been predicted that the occurrence of CHF may soon reach epidemic proportions.3,4

A study of heart failure (HF) in the Scottish population showed that hospital discharge rates for CHF increased by almost 60% between 1980 and 1990.3 The researchers estimated that, at the time of reporting, the number of hospitalizations for CHF was similar to those for myocardial infarction (MI).3 A study conducted at about the same time calculated that the financial burden of CHF in the UK was almost equal to those of stroke and asthma combined.5 Current estimates suggest that almost 1 million annual admissions to US hospitals are for CHF-related disorders.6

The long-term prognosis associated with CHF is poor.7 It is estimated that half of all patients diagnosed with CHF will die within 4 years, whereas of those diagnosed with severe CHF, more than 50% will die within 1 year.1,3,4 The 5-year survival rate in CHF is lower than that associated with MI and a number of key malignancies, and is surpassed only by lung cancer.4

CHF occurs most commonly in elderly patients, in whom ischaemic heart disease and hypertension are the most important aetiologic factors.1,8 Diabetes is widespread in the elderly population and may also contribute substantially to the burden of CHF, accounting for more than 30% of HF-related hospitalizations.8,9

Quality of life (QoL) for patients surviving HF-related hospitalizations remains poor.4 In studies comparing the effects of major chronic illnesses (diabetes, arthritis, HF, and hypertension), HF had the greatest negative impact on QoL.5 Patients with CHF, and particularly those in advanced stages of the disease, suffer a number of symptoms, of which fatigue and dyspnoea are the most troubling.10 The disease can also lead to the disruption of daily functioning and increasing dependence on carers.10 The discomfort and distress suffered by end-stage CHF patients may approach that felt by terminal cancer patients.2

CHF is, thus, a serious public health problem. In this review, the epidemiology of CHF will be discussed and European guidelines and current treatment strategies for its pharmacological management will be outlined.


   Epidemiology of CHF
Top
 Abstract
 Introduction
 Epidemiology of CHF
Pharmacological treatment and...
 Summary
 Acknowledgements
 References
 
Incidence and prevalence
HF is largely a disease of old age and represents the leading hospital diagnosis in older adults.7 Both the incidence and the prevalence of CHF increase sharply with increasing age such that patients aged >75 face a much greater risk of developing this condition.2,8 Estimates calculated within the last decade suggest a prevalence of ~1–2% in the overall population and >10% in the elderly population.2,5

It has been estimated that there are currently 6.5 million CHF patients in Europe and 5 million in the USA, and these numbers are increasing because of the ageing of the global population and the ability of increasing numbers of individuals to survive to an age when CHF is likely to become a problem.7,11 In addition, the availability of improved medical technologies has enabled more effective treatment of acute coronary syndromes and has conferred improved survival rates in patients following MI, the most powerful predictor of left ventricular systolic dysfunction (LVSD) and risk of HF.2,12,13 As a result, the absolute number of individuals living with compromised cardiac function and clinical CHF is expected to rise dramatically over the next few decades.2

Diagnostic challenges
Awareness of the growing burden of CHF is increasing; however, there is a current lack of comparative international epidemiological data for this condition such that its exact incidence and prevalence remain largely unknown and probably underestimated.14 This stems from a number of diagnostic and coding challenges, which render the appropriate allocation of resources problematic and may contribute to undertreatment.12,15

HF is a complex syndrome that can result from a number of disease processes including coronary artery disease, hypertension, arrhythmias, valve abnormalities, pericardial disease, or specific or idiopathic cardiomyopathies.1,15

There is currently no universal definition of CHF and no gold standard for its diagnosis.14–16 This is especially true for patients with CHF presenting with normal LV function.17 Low specificity of symptoms, inadequate use of diagnostic tests, and the presence of asymptomatic disease in many patients make accurate diagnosis problematic, especially in women, the elderly, and the obese.1,12,16 Such challenges are reflected by the findings of European studies. A UK investigation revealed that up to 70% of patients with a primary care diagnosis of CHF showed no evidence of the disease on further assessment,15 whereas 60% of patients with LVSD in the Rotterdam Study showed no signs or symptoms of CHF.16

Many CHF patients present with comorbidities, which may make the interpretation of clinical signs and symptoms difficult.1 Elderly sufferers, in particular, present a challenge as these patients are likely to have comorbid conditions, are often investigated less intensively and may have poorly documented medical histories.15

A number of investigations are recommended by the European Society of Cardiology (ESC) for the accurate diagnosis of CHF. Ideally, all suspected patients should undergo comprehensive investigations involving clinical examination, electrocardiography, chest X-ray, and echocardiography. Additional tests, such as coronary angiography, may also be needed to assess aetiology.1 However, necessary diagnostic procedures are not always performed because of the lack of availability or negligence. The ESC EuroHeart Survey on HF revealed that cardiac function was not assessed in one-third of surveyed European patients, representing a substantial diagnostic deficiency.14 Note that echocardiography, recommended for the assessment of LV function, is used with considerable variation around Europe and is not available to many physicians.1,14

Cases of CHF are reported on the basis of diagnostic coding according to the international classification of disease (ICD) system. As aetiological diagnosis is often used, CHF may be reported as a secondary diagnosis or may not be reported at all, thus reports may underestimate the extent of CHF. An evaluation of the ICD system has shown that approximately one-third of patients with clinical evidence of an acute episode of HF were missed by the first three ICD diagnostic codes.18 If this is the case, then the coding of HF patients in discharge records and death certifications is likely to be inaccurate and the mortality, hospitalizations, and costs associated with HF substantially underestimated.15,18

Owing to these diagnostic and coding challenges, data have shown as much as a four-fold difference in the prevalence of HF between countries, reflecting substantial differences in definitions of HF and diagnostic accuracy.19 These challenges need to be addressed through the establishment of specific HF registries and the performance of surveys to reflect the spectrum of HF in the general population.15,19


   Pharmacological treatment and ESC Guidelines for the management of CHF
Top
 Abstract
 Introduction
 Epidemiology of CHF
 Pharmacological treatment and...
Summary
 Acknowledgements
 References
 
Numerous pharmacological therapies are available for the management of CHF; however, many patients remain undertreated. Thus, the implementation of evidence-based strategies is important to ensure that patients receive optimal treatment wherever possible.

Evidence-based medicine represents an effective way of providing high-quality, cost-effective care.20 The ESC Guidelines for the Diagnosis and Treatment of Chronic Heart Failure (2001)1 were developed to provide clinicians with guidance in the diagnosis and management of CHF patients using evidence-based approaches. In the following sections, recommendations from the 2001 ESC Guidelines for the pharmacological management of CHF are presented together with supportive data from more recent clinical trials. It was recommended that these therapies should be prescribed, where appropriate, in conjunction with a number of non-pharmacological strategies, including patient and carer education, weight control, adoption of a low-sodium diet, restricted fluid intake, physical exercise, and drug counselling.1

Angiotensin-converting enzyme inhibitors
Angiotensin-converting enzyme (ACE) inhibitors were recommended in the 2001 guidelines as a first-line therapy in patients with reduced LV systolic function [ejection fraction (EF)<40–45%]. They should be uptitrated to the dosages shown to be effective in large controlled trials in HF and not based on symptomatic improvement alone.1

Data from a number of clinical studies show that ACE-inhibitors prolong survival, reduce hospitalizations and disease progression, improve QoL, and increase exercise capacity in symptomatic HF patients, thus supporting their recommendation as a first-line therapy for the treatment of this condition.1,21–26

The CONSENSUS (Cooperative North Scandinavian Enalapril Survival Study) and SOLVD (Studies of Left Ventricular Dysfunction) trials indicate that ACE-inhibitors improve survival in patients in all functional classes [New York Heart Association (NYHA) I–IV].21,22 Data also suggest that survival benefits are sustained24,27 but are likely to be greater in those with more severe LVSD.25 No differences are thought to exist according to race, and appreciable reductions in mortality may also be achieved in patients with concomitant diabetes.25

Diuretics
The 2001 guidelines stated that diuretics are essential for symptomatic treatment when fluid overload is present and manifest as pulmonary congestion or peripheral oedema. The use of diuretics results in rapid improvement of dyspnoea and increased exercise tolerance. Diuretics should always be administered in combination with ACE-inhibitors.1

Diuretics, and particularly loop diuretics, are regarded as a first-line treatment in CHF for symptomatic relief through the reduction of pulmonary congestion.1 Increasing dosages may be required as CHF worsens, and agents may be used in combination (i.e. thiazide+loop diuretic) in severe disease.1

A meta-analysis of 18 randomized clinical trials of diuretics has shown that these agents reduce mortality, worsening HF and hospitalizations, and significantly improve exercise function in HF patients.28 The meta-analysis estimated that 80 deaths could be avoided for every 1000 HF patients treated with diuretics.28

Beta-blockers
Beta-blockers were recommended in the guidelines for the treatment of all patients with stable, mild, moderate, and severe HF from ischaemic or non-ischaemic cardiomyopathies and reduced LVEF (NYHA classes II–IV) on standard treatment, including diuretics and ACE-inhibitors unless there is a contraindication. In patients with LVSD, with or without symptomatic HF, following an acute MI, long-term beta-blockade was recommended in addition to ACE-inhibition to reduce mortality.1

Beta-blockers are associated with substantial survival benefit in CHF, achieving improvements in NYHA class and reductions in mortality, sudden cardiac death and hospitalizations regardless of age, race, gender, or LVEF.25,29–35 A number of beta-blocker trials have been terminated prematurely because of considerable evidence supporting their efficacy.29,30,36–38

In recent mortality trials, carvedilol was associated with a 23% improvement in post-MI survival in patients with asymptomatic HF (EF<40%) (CAPRICORN)32 and a 35% mortality reduction in patients with severe HF and LVEF <25% (COPERNICUS).33,38 However, few data are available regarding the use of beta-blockers in patients with preserved systolic function (PSF) or acute HF.34

Aldosterone antagonists
Aldosterone antagonists were recommended in the 2001 guidelines, in addition to ACE-inhibition and diuretics, to improve survival and morbidity in advanced HF (NYHA classes III and IV).1

Following its initial use as a high-dose diuretic, spironolactone has shown efficacy as a low-dose therapy through the suppression of aldosterone production, achieved only transiently by ACE-inhibitors.1,39

In RALES (Randomised Aldactone Evaluation Study), low-dose spironolactone, when added to standard medical therapy (ACE-inhibitor+loop diuretic+digoxin), conferred a 30% reduction in the risk of death and a 35% reduction in the risk of hospitalization for worsening HF in patients with advanced HF and LVSD.39 Subsequently in EPHESUS (Eplerenone Post-acute Myocardial Infarction Heart Failure Efficacy and Survival Study), eplerenone reduced overall mortality [relative risk reduction (RRR), 15%], cardiovascular mortality (RRR, 13%), sudden cardiac death (RRR, 21%), and hospitalizations for HF (RRR, 15%) in post-MI HF patients with LVSD receiving optimal medical therapy.40 The concurrent 4E study showed the benefits of combination therapy with eplerenone and enalapril through significant reductions in LV mass, blood pressure, and albuminuria in patients with LV hypertrophy.41 The mode of action of these agents in HF remains unclear; however, it seems likely that it is due to their diuretic effects in conjunction with specific mechanisms of aldosterone blockade.28,40

Angiotensin II receptor antagonists
The ESC 2001 Guidelines advised that angiotensin II receptor antagonists (ARBs) might be considered in patients who do not tolerate ACE-inhibitors for symptomatic treatment. At the time of development of the guidelines, it was unclear whether ARBs were as effective as ACE-inhibitors for mortality reduction. However, it was known that in combination with ACE-inhibition, ARBs may improve HF symptoms and reduce hospitalizations for worsening HF.1

In fact, few data were available concerning the efficacy of ARBs in HF prior to the development of the ESC 2001 Guidelines. Data from Val-HeFT (Valsartan Heart Failure Trial) demonstrated a significant reduction in hospitalizations and improvement in QoL with valsartan in addition to background therapy in HF.42,43 Both Val-HeFT and ELITE II (Evaluation of Losartan In The Elderly II) suggested that ARBs may be beneficial in HF patients in whom ACE-inhibitors are not tolerated.43–45 However, both studies suggested that ARBs are not superior to ACE-inhibitors in reducing mortality in HF and may be associated with negative effects if a beta-blocker is added to the treatment regimen.42–44 These modest findings resulted in a lack of firm recommendations concerning the use of ARBs in HF, and clinicians were advised to consider their use in ACE-intolerant patients or in combination with ACE-inhibitors to achieve more complete inhibition of angiotensin II.1

The CHARM programme (Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity) investigated the use of candesartan in CHF patients with LVSD, PSF, ACE intolerance or in those already receiving standard therapy (diuretic+ACE-inhibitor+beta-blocker).46–50 Candesartan was associated with reductions in cardiovascular mortality and hospitalizations in all patients with LVSD.46–48,50,51 A similar trend was shown for patients with PSF.49 The programme also indicated that the addition of an ARB to an ACE-inhibitor plus beta-blocker-based treatment regimen is associated with improved outcomes and few deleterious effects, indicating the efficacy and safety of triple therapy.47

The 2005 ESC Guidelines for the Diagnosis and Treatment of Chronic Heart Failure52 are now available. These guidelines provide updated guidance on the optimal use of pharmacological agents in CHF, using evidence-based approaches based on the most recent clinical trial data.


   Summary
Top
 Abstract
 Introduction
 Epidemiology of CHF
 Pharmacological treatment and...
 Summary
Acknowledgements
 References
 
CHF is an increasingly prevalent condition that confers poor life expectancy, reduced QoL and a high risk of hospitalization on patients, and a considerable burden of care on healthcare professionals. Despite its high mortality and morbidity, many patients do not receive accurate diagnoses or optimum pharmacological treatments.

A range of highly effective agents are available for the management of this condition, supported by a wealth of clinical trial data. Widespread dissemination and implementation of evidence-based diagnosis and treatment guidelines are crucial if prognosis and QoL are to be improved in patients with this devastating condition.


   Acknowledgements
Top
 Abstract
 Introduction
 Epidemiology of CHF
 Pharmacological treatment and...
 Summary
 Acknowledgements
References
 
This work was supported by an unrestricted educational grant from Takeda Pharmaceutical Company Limited. Content from the 2001 ESC CHF Guidelines1 is cited with permission granted by the ESC.

Conflict of interest: none declared.


   References
Top
 Abstract
 Introduction
 Epidemiology of CHF
 Pharmacological treatment and...
 Summary
 Acknowledgements
 References
 

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