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European Journal of Heart Failure 2004 6(6):801-806; doi:10.1016/j.ejheart.2004.09.003
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© 2004 European Society of Cardiology

Aetiology, comorbidity and drug therapy of chronic heart failure in the real world: the EPICA substudy

Fátima Ceiaa,b,*, Cândida Fonsecab,c,1, Teresa Motad,e,2, Humberto Moraisf,g, Fernando Matiasf,g, Catarina Costaf,g and António G. Oliveirah,i

a Department of Medical Therapeutics, Medical Sciences School New University of Lisbon, Portugal
b Serviço de Medicina, Hospital S. Francisco Xavier 1400 Lisboa, Portugal
c Department of Internal Medicine, Medical Sciences School New University of Lisbon, Lisbon, Portugal
d Department of Cardiology, Medical Sciences School New University of Lisbon, Lisbon, Portugal
e Serviço de Cardiologia, Hospital Pulido Valente 1750 Lisboa, Portugal
f EPICA Working Group Portugal
g Grupo de Investigação EPICA Av. António Augusto de Aguiar 128, 1050 Lisboa, Portugal
h Datamedica Ltd. Lisbon, Portugal
i Datamedica R. Garcia de Orta 70, 2 D, 1200 Lisboa, Potugal

* Corresponding author. Av. Grão Vasco 47-1° Esq. 1500-336 Lisboa, Portugal. Tel.: +351 21 760 45 73; fax: +351 21 301 7958.. E-mail address: fatima.ceia{at}sapo.pt


   Abstract
Top
 Notes
 Abstract
1. Introduction
 2. Methods and population
 3. Results
 4. Discussion
 References
 
Background: Chronic heart failure (CHF) is common and is frequently managed by primary care physicians (PCPs). Despite the European Society of Cardiology (ESC) Guidelines, standard treatments for CHF are frequently underutilised, particularly in primary care.

Aim: To evaluate current drug therapy for CHF in adults with HF diagnosed according to ESC guidelines in the context of the EPICA study. Aetiological features and therapy relevant comorbidities were also analysed.

Methods: EPICA was a community-based epidemiological study conducted in mainland Portugal. The study involved 365 primary care physicians, who evaluated 6300 primary care attendees aged over 25 years. CHF was diagnosed by clinical and echocardiography criteria according to ESC guidelines.

Results: Total of 551 cases of CHF were identified, with a mean age of 65±9 years. The estimated overall prevalence of CHF in the Portuguese population was 4.4%; 1.3% with and 1.7% without left ventricular systolic dysfunction (LVSD). There are 6,280,792 people aged >25 years in Portugal, which extrapolates to 261,400 cases of heart failure. About 80% of patients had a history of hypertension, 39% had a history of coronary artery disease and 15% had atrial fibrillation. Only 58% of patients were on angiotensin-converting enzyme (ACE) inhibitors and 7% on beta-blockers. The type of ventricular dysfunction, age and presence of renal failure had little effect on prescription rates. Diuretics were prescribed in 78%. Thiazides were used more frequently in those with preserved systolic function and frusemide in those with left ventricular systolic dysfunction. Digoxin was prescribed more often to patients with than without left ventricular systolic dysfunction (34% vs. 17%; p=0.02). Long-acting nitrates were prescribed to 20% and amiodarone to 8% of patients.

Conclusion: The EPICA study, as in other studies in primary care in Europe, particularly the IMPROVEMENT study, suggests that greater efforts are required to improve training of primary care teams in the management of CHF.

Key Words: Heart failure • Primary care • Guidelines • Treatment

Received July 6, 2004; Accepted September 8, 2004


   1. Introduction
Top
 Notes
 Abstract
 1. Introduction
2. Methods and population
 3. Results
 4. Discussion
 References
 
Chronic heart failure (CHF) is common [1-8]. In Portugal, the EPICA study showed that CHF has a global estimated prevalence of 4.4% amongst adults older than 25 years [6]. CHF due to primary ventricular dysfunction can be divided into two distinct entities: CHF due to left ventricular systolic dysfunction (LVSD) and CHF with preserved left ventricular function, which is, according to some authors, equivalent to diastolic ventricular dysfunction [10-13]. CHF has great social impact, as it is a prevalent disease with high mortality, causing severe incapacity and high costs [2,14-16]. The benefit of angiotensin-converting enzyme (ACE) inhibitors, and more recently, beta-blockers, on mortality, morbidity and hospitalisation of patients with CHF due to LVSD has been demonstrated, and these drugs are strongly recommended in the guidelines [17-24]. Treatment of CHF with preserved left ventricular function is still empirical, based on aetiology and pathophysiological changes [12,13,25]. Despite evidence and guidelines, probably only a minority of patients with CHF are being correctly treated with ACE inhibitors and beta-blockers [26-33].

The aim of the present study was to evaluate current drug therapy of CHF in primary care in Portugal, as part of a prospective epidemiological study. Aetiological features of the syndrome and therapy relevant comorbidity were also analysed.


   2. Methods and population
Top
 Notes
 Abstract
 1. Introduction
 2. Methods and population
3. Results
 4. Discussion
 References
 
The EPICA study was a community based epidemiological study, which took place in mainland Portugal between April and September 1998, shortly before publication of the majority of the landmark mortality trials of beta-blockers but many years after publication of the landmark trials of ACE inhibitors. The study involved 365 primary care physicians (PCPs) who evaluated 6300 subjects aged over 25 years attending primary health care centers in the community. The design and sampling method has been described in detail elsewhere [6,34]. All patients with a possible or probable diagnosis of CHF according to the Boston clinical scores [35] had an ECG, chest X-ray, echocardiogram and blood tests as suggested by European Society of Cardiology (ESC) Guidelines, to establish the presence and likely cause of heart failure or to support alternative diagnoses and identify comorbidities. CHF was diagnosed by clinical and echocardiographic criteria according to ESC Guidelines [36]. Current prescription of diuretics, digoxin, ACE inhibitors, amiodarone, beta-blockers and nitrates was recorded. However, questions about platelet antiaggregants, anticoagulants, spironolactone and calcium channel blockers were not included.

For comparison of prevalences between groups, the Pearson's Chi-squared test for two-way tables with the Rao-Scott correction for the surveys having complex drawing was used [37].


   3. Results
Top
 Notes
 Abstract
 1. Introduction
 2. Methods and population
 3. Results
4. Discussion
 References
 
Total of 551 individuals with CHF were identified: 208 men and 343 women, with an average age of 65 years (95% CI: 62-68). The estimated global prevalence of CHF in the Portuguese adult population was 4.4%: 4.3% for men (95% CI: 3.2-5.5%) and 4.4% for women (95% CI: 3.6-5.1%). Prevalence increased with age [6]. The estimated prevalence of CHF with left ventricular systolic dysfunction was 1.3% (95% CI: 2.2-3.8) and of CHF with preserved systolic function was 1.7% (95% CI: 1.4-2.0). Thus, in Portugal, we estimate that there are >140,000 patients aged >60 years with CHF (Table 1) [6].


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  		Table 1 Estimated prevalence of CHF in patients aged over 60 years (absolute numbers)

 
The estimated prevalence of aetiological and/or risk factors are listed in Table 2. Arterial hypertension was the most frequent risk factor for CHF, especially in patients without left ventricular systolic dysfunction, followed by coronary artery disease, especially in patients with left ventricular systolic dysfunction (Table 2). The estimated prevalence of renal failure was 0.8±0.6% among patients with left ventricular systolic dysfunction and 7.5±2.5% among those with preserved systolic function (p=0.007). The population estimate of the distribution of CHF by NYHA functional classes is similar in patients with and without left ventricular systolic dysfunction: 35% vs. 39% in class I, 35% vs. 24% in class II, 22% vs. 18% in class III and 4% vs. 7% in class IV.


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  		Table 2 Estimated prevalence of risk factors/etiologies of CHF in Portuguese population

 
The population estimate suggests that 78±4% (standard error, S.E.) of patients were treated with loop or thiazide diuretics, 58±4% with ACE inhibitors, 29±4% with digoxin, 8±1% with amiodarone, 20±2 with nitrates and 6±2% with beta-blockers (Table 3) in 1998. Therapy with ACE inhibitors was similar in patients with and without LVSD, but digoxin and nitrates were used more often in patients with LVSD (Table 3).


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  		Table 3 Current medication for CHF in primary care (estimated percentages for Portuguese population)

 
Among patients with CHF with or without LVSD, ACE inhibitor prescription was independent of age (60%, 57% and 64%, respectively in age groups <65 years, 65-74 years, and >75 years, p=NS) and of the diagnosis of renal failure (61% with vs. 70% without renal failure, p=NS). The use of digoxin and amiodarone, but not of beta-blockers, was more frequent amongst patients with atrial fibrillation (Table 4). Patients with more severe symptoms were more likely to be prescribed ACE-inhibitors, digoxin, frusemide, amiodarone and nitrates (Table 5).


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  		Table 4 Drug therapy and atrial fibrillation in patients with CHF in primary care

 


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  		Table 5 Drug therapy for chronic heart failure (left ventricular systolic dysfunction and preserved systolic function) in primary care, according to functional classes

 

   4. Discussion
Top
 Notes
 Abstract
 1. Introduction
 2. Methods and population
 3. Results
 4. Discussion
References
 
Correct and early treatment of CHF can increase survival, decrease hospitalisation and improve patients' clinical condition and quality of life. The principles of management of CHF have been laid out in guidelines [17,18]. However, their implementation in clinical practice, especially perhaps in primary care, seems to be suboptimal [32,33].

The prevalence of hypertension, an important risk factor for the development of heart failure due to systolic or to diastolic ventricular dysfunction [9,25], is high in Portugal. Coronary artery disease was a risk factor for heart failure in about 40% of the patients. These data are consistent with the IMPROVEMENT study [33] and EuroHeart Failure Surveys and suggest that much of the national Portuguese data are relevant to patients in many other ESC countries [38-40].

The difference between selected CHF patient populations with LVSD included in large randomised trials and ‘real-world’ CHF patients is a classical problem of today's evidence-based medicine [26-29,32]. This difference, compounded by other factors such as lack of training, lack of resources, fear of adverse effects and polypharmacy and, of course, the higher prevalence of CHF with preserved systolic function [6,12,41], probably accounts for the failure to prescribe effective therapy to many patients.

The EPICA study showed that 58% of all patients with CHF in primary care were treated with ACE inhibitors, although only 47% of those with LVSD. As drug doses were not recorded in the EPICA study, we do not know whether the target dosage of ACE inhibitors was achieved. The prescription of ACE inhibitors in Portugal appears similar or higher to that previously reported in many other European countries [7,27,32,33,42,43]. It is possible that prescription rates have improved, but, in the US Cardiovascular Health Study, amongst patients >65 years, ACE inhibitor prescription fell from 46% to 42% amongst new cases of CHF between 1990 and 1995 [28]. In the IMPROVEMENT programme, conducted during 1999-2000, ACE inhibitors were prescribed to 60% of all CHF patients, varying from 70% in Italy to 51% in Spain [33]. However, this survey might have been prone to physician and patient selection bias. It is likely to have enrolled patients, about whom physicians were more confident of the diagnosis, with more severe symptoms and receiving more treatment.

In some studies, older age, more severe disease and the existence of comorbidities were identified as factors reducing the prescription of ACE inhibitors in patients with systolic dysfunction [30,44,45]. This was not confirmed in the EPICA study.

The IMPROVEMENT programme suggested that only a minority of primary care physicians distinguish between systolic and diastolic left ventricular dysfunction as a cause of CHF, varying from 65% in Italy to 26% in the UK [33]. On the other hand, these two types of CHF are not easy to distinguish based on clinical criteria, and Guidelines provide little information on the treatment of CHF with preserved left systolic function (PLVSF) [12,13,23,24]. The CHARM-preserved trial showed equivocal benefits from candesartan, an angiotensin receptor blocker, in this clinical setting [46,47]. The outcome of a large trial of the ACE inhibitor perindopril is awaited [25]. However, many clinicians believe that treatment improves symptoms and prognosis in both situations [33]. This might explain the similar use of ACE inhibitors among patients with CHF and preserved left ventricular function in the EPICA study. The higher prevalence of arterial hypertension within this latter group may contribute as well.

Primary care physicians were taught, until recently, that beta-blockers were contraindicated in patients with CHF. Beta-blockers have only been recommended in ESC guidelines since 1997, although many key landmark trials were not published until 1999 [23,24]. It is therefore understandable that in EPICA, in 1998, only 7% of patients were treated with this drug class. In the IMPROVEMENT survey, 50% to 90% of the primary care physicians believed that beta-blockers improved symptoms or/ and prognosis but, overall, only one-third were prescribed these agents, although with considerable national variation [33]. In addition, it appeared that many patients were receiving beta-blockers for the treatment of hypertension or coronary artery disease rather than heart failure. Moreover, starting and titrating these drugs to target doses is complex and time-consuming which may reduce their use, as every Portuguese PCP has to care for at least 1500 people [48] of whom perhaps 40 will have heart failure. Fear of side effects, particularly in patients with respiratory disease, may reduce use further.

Diuretics improve symptoms, although there is no evidence that they improve survival [23,24]. In the EPICA study, >75% of patients were on diuretics of whom 2/3 had persisting symptoms (NYHA classes II to IV). The more frequent use of thiazides in patients with preserved left ventricular systolic function may reflect the higher prevalence of hypertension in this group and their use as antihypertensive agents.

Digoxin does not improve survival of patients with CHF, with or without LVSD, and there is little evidence that it improves symptoms [23,24,49]. Nevertheless, it plays an important role in the control of the heart rate of patients with atrial fibrillation [50]. In EPICA, one-third of patients with CHF and systolic dysfunction were on digoxin, which is similar to that observed in other studies [32,33,41]. Digoxin was also prescribed to 9% of patients with preserved ventricular function although only half of them had atrial fibrillation. Vasan et al. [12] also reported a significant number of CHF patients with preserved systolic function on digoxin.

The higher incidence of nitrate prescription among patients with CHF and systolic dysfunction may be explained by the higher prevalence of coronary artery disease in this group. The number of patients treated with amiodarone was low as would be expected in the primary care setting.

The EPICA study provides an update of primary care physicians' knowledge about CHF management. There is a need for better communication between heart failure specialists and primary care physicians. Heart failure is common. More than half of patients with CHF have preserved left ventricular systolic function, a group in whom further objective evidence of cardiac disease would be desirable. Many patients have inadequate symptom control. ACE inhibitors and beta-blockers are underprescribed in patients with systolic dysfunction. These aspects of care and the promotion of ESC guidelines should be included in future educational programmes to implement an evidence-based approach to the management of CHF.


   Acknowledgements
 
The EPICA Project is supported by Servier Research Group and has the scientific sponsorship of the Portuguese Society of Cardiology and of the Working Group on Heart Failure of the European Society of Cardiology. We are especially grateful to Prof. John G. Cleland for his advice. The authors are indebted to the EPICA investigators, without whom this work would not have been possible. We are grateful to Dr. Micaela Seeman Monteiro for revising the manuscript.


   Notes
Top
 Notes
Abstract
 1. Introduction
 2. Methods and population
 3. Results
 4. Discussion
 References
 
1 R. Salvador Barata Feyo n° 1 r/c-D.to2780-335 Oeiras, Portugal. Back

2 R do Loreto n° 34-3° 1200 Lisboa, Portugal. Back


   References
Top
 Notes
 Abstract
 1. Introduction
 2. Methods and population
 3. Results
 4. Discussion
 References
 

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