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European Journal of Heart Failure 2005 7(4):657-661; doi:10.1016/j.ejheart.2004.11.011
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© 2005 European Society of Cardiology

Influence of age and in-patient care on prescription rate and long-term outcome in chronic heart failure: a data-based substudy of the EuroHeart Failure Survey

Martin Hülsmann*, Rudolf Berger, Deddo Mörtl and Richard Pacher

Department of Cardiology, University of Vienna Währinger Gürtel 18-20, A-1090 VIENNA, Austria

* Corresponding author. Tel.: +43 1 404004616; Fax: +43 1 4081148. E-mail address: martin.huelsmann{at}meduniwien.ac.at


   Abstract
Top
 Abstract
1. Introduction
 2. Methods
 3. Results
 4. Discussion
 References
 
Aims: To evaluate the prescription rate of neurohumoral drugs in chronic heart failure patients and the factors influencing prescription rates. Outcomes and their predisposing factors were also investigated.

Methods and results: Of 1482 consecutive patients admitted to 3 Austrian hospitals participating in the EuroHeart Failure Survey, 341 were included in this data-based substudy. Follow-up time to evaluate outcome was up to 46 months. The prescription rates of renin–angiotensin (RAAS) antagonists and β-blockers at the time of discharge were evaluated. The overall prescription rate and dosage were lower than the recommended levels. Hospitals with cardiac care had a significantly higher prescription rate than those without (p<0.001). Patients older than 75 years received significantly less therapy (p<0.001) and a lower dosage of RAAS antagonists (p<0.01) than younger patients. Younger patients were treated more intensively in hospitals with cardiac care (p<0.05). Patients aged >75 years were under-treated, independent of the hospital (n.s.). Multivariate analysis showed that age was the most influencing factor on survival (X2 15.5, p<0.0001). Additional influencing factors of long-term survival were type of the ward (X2 7.9, p<0.005) and pharmacologic treatment (X2 6.2, p<0.02).

Conclusion: Patients with chronic heart failure are still under-treated in clinical practice. Younger patients benefit from hospitals with specialized cardiac care. Elderly patients are obviously under-treated compared with younger patients. Of several clinical parameters, age was the only independent variable predicting long-term survival.

Key Words: Chronic heart failure • Therapy • Age • Specialty care

Received September 15, 2004; Revised November 23, 2004; Accepted November 25, 2004


   1. Introduction
Top
 Abstract
 1. Introduction
2. Methods
 3. Results
 4. Discussion
 References
 
Chronic heart failure has become a major problem in internal medicine. Based on clinical studies, ACE inhibitors and β-blockers are recommended as standard therapy [1]. The EuroHeart Failure Survey investigated, in more than 11,000 patients, the implementation of this therapy in clinical practice [2,3]. It was found that ACE inhibitors are only prescribed in 61.8% and β-blockers in 36.9% of cases. Only 17.2% of patients received combination therapy [3]. This is far from the optimal situation. Other factors such as type of hospital ward, etiology, age and co-morbidity also influence the prescription rate. Data from the Austrian centers, which participated in the EuroHeart Failure Survey, are in line with those for the entire study population [3]. Follow-up mortality data for the total study cohort are not yet available. We investigated the long-term mortality of our patients in order to (a) define the severity of the disease and the investigated subgroups and (b) to investigate the influence of therapy and other factors influencing prescription rates on mortality.


   2. Methods
Top
 Abstract
 1. Introduction
 2. Methods
3. Results
 4. Discussion
 References
 
2.1. Patients
Three Austrian hospitals participated in the EuroHeart Failure Survey. One hospital had a cardiac care department, while two had general internal medicine departments (GIM). One study monitor evaluated every hospital in-patient over a predefined time span of 4–6 months. Of 1482 consecutive in-patients, 341 patients were included in the study: 155 patients were treated in a cardiac care department and 186 were treated in a GIM department. Inclusion criteria were diagnosed heart failure within the last 3 years, the use of loop diuretics if not for primary renal insufficiency, or administration of any heart failure treatment. Details of the study protocol are described elsewhere [2]. Data were obtained at the time of discharge or death in the hospital. The trial was conducted in accordance with the Declaration of Helsinki and approval from the local ethics committee was obtained. All patients gave written informed consent.

Patients were stratified according to the type of hospital ward:

Group 1 comprised those admitted to a ward with cardiac care
Group 2 comprised those admitted to a ward with GIM care and also according to age:
Group A consisted of those 75 years old or younger
Group B consisted of those older than 75 years.

Patients were followed until September 2003, for a period of up to 46 months. Outcome was evaluated by phone calls.

2.2. Statistics
Continuous variables are expressed as means±standard deviation. For group comparison of continuous variables, a two-tailed Student's t-test was used.

Categorical data were compared against a chi-square distribution. Kaplan–Meier survival analysis and a log-rank test were used to compare mortality over time between treatment groups (combined RAAS antagonists and β-blocker vs. single or no therapy), between different types of wards, between older and younger patients, and treatment groups in the elderly.

A Cox proportional hazards regression analysis was performed to identify independent predictors of long-term survival. The model was designed in a stepwise fashion; the p-value for entering and staying in the model was set at 0.05.

The following variables were included: age, combined neurohumoral therapy, type of ward (cardiac/GIM), sodium, creatinine, CAD, weight, sex, systolic blood pressure, atrial fibrillation, hypertension, diabetes and history of ventricular tachycardia.

All statistical analyses were performed using SAS (SAS Institute Inc., Cary, NC). A p-value of <0.05 was considered to be statistically significant.


   3. Results
Top
 Abstract
 1. Introduction
 2. Methods
 3. Results
4. Discussion
 References
 
3.1. Patient characteristics
Of 1482 consecutive in-patients, 341 were included in the study. Thus, 23% of patients admitted to an internal medicine ward had heart failure. The patients' mean age was 73±13 years and the sex distribution was equal (49% female). The primary diagnosis at discharge was heart failure in 45% of cases. Due to the rather advanced mean age of the patients, the level of co-morbidities was high: 56% of patients had hypertension, 32% diabetes mellitus, 15% respiratory diseases, 16% infectious diseases, 12% cerebral ischemia and 11% had renal insufficiency. Details have been published elsewhere [2,3].

3.1.1. Prescription rate
3.1.1.1. Total cohort
The patients' treatment at the time of discharge was evaluated. 26% of the patients received no heart failure treatment, 39% received RAAS antagonists (ACE inhibitors or angiotensin II blockers) and 11% received a β-blocker as monotherapy. Only 24% of patients received a combination of a RAAS antagonist and a β-blocker as recommended by the guidelines of the European Society of Cardiology [1].

The mean dosage of ACE inhibitors was 17±16% of the maximum recommend dose. Angiotensin II antagonists were dosed to 54±40%, while β-blockers were dosed to 56±69% of the maximum recommended dose.

3.1.1.2. Differences by hospital
The treatment of patients in the hospital with cardiac care (group 1, n=155) was compared with the treatment of patients in the hospitals with no cardiac care (group 2, n=186).

18% of group 1 received no therapy, 32% received a single RAAS antagonist and 14% received β-blocker monotherapy. Combined treatment was given in 36% of cases.

In group 2, 32% received no heart failure therapy, 46% received RAAS antagonists and 9% received β-blockers as monotherapy. Only 13% received both RAAS antagonists and β-blockers as recommended. The difference between groups was statistically significant (p<0.001).

The two groups did not differ in respect of the mean dosage of the drugs.

3.1.1.3. Differences by age
Therapy for patients aged 75 years or less (group A, n=172) was compared with therapy for those older than 75 years (group B, n=169).

Only 15% of younger patients received no specific therapy, 32% received a single RAAS antagonist and 15% received a β-blocker, while 38% received combined therapy.

In the older age group, 37% of patients aged 75 years or more remained untreated, 47% received RAAS antagonists and 7% received a β-blocker as single therapy. Only 9% received combined therapy.

The difference between the groups was statistically significant (p<0.001).

The difference in the dosage of ACE inhibitors between groups was statistically significant (group A 20±17% vs. group B 14±13% of the recommended dosage, p<0.01), while the dosages of angiotensin II blockers and β-blockers were comparable (n.s.).

3.1.1.4. Differences by hospital, depending on age
Younger patients were more likely to be admitted to a cardiac ward (76% vs. 26%, p<0.001). Depending on the patients' age, the therapies differed significantly in the two types of hospital (p<0.001).

Younger patients were treated more intensively in a hospital with cardiac care (p<0.05; 14% vs. 19% no treatment, 30% vs. 38% single RAAS antagonists and 45% vs. 23% combined treatment).

Elderly patients were under-treated, independent of the type of hospital (n.s.; 33% vs. 38% no treatment, 42% vs. 48% single RAAS antagonist and 8% vs. 10% combined treatment.).

3.1.2. Reasons for no treatment
Patients were evaluated to ascertain whether no treatment was due to contraindications to the drug.

Contraindications for RAAS antagonists were defined as follows: low blood pressure, impaired renal function or cough.

Contraindications for β-blockers were a low heart rate, obstructive lung disease, decompensated heart failure and peripheral arterial occlusive disease.

Of 113 patients who were not receiving ACE inhibitors, only 29 (26%) had a contraindication. Of those patients (n=221) who were not receiving β-blocker therapy, 133 (60%) had contraindications (Table 1).


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  		Table 1 Number of patients with contraindications for ACE inhibitors or β-blockers

 
Among patients younger than 75 years, 9 of 50 (18%) patients not receiving ACE inhibitors (or angiotensin II blockers) had a contraindication, whereas 35 of 81 patients (43%) not receiving β-blockers had a contraindication.

The number of contraindications increased with age, the difference being statistically significant for β-blockers (p<0.001). Twenty of 72 patients above 75 years, not receiving ACE inhibitors (or angiotensin II blockers), had a contraindication (28%). Of patients older than 75 years not receiving β-blocker therapy, 97 of 139 had a contraindication (70%). The main contraindication for ACE inhibitors in the elderly was renal dysfunction (60%) and for β-blockers was decompensated heart failure (54%).

3.2. Mortality
The overall mortality was 51%. Patients older than 75 years were more likely to die (68% vs. 31%, p<0.001). Patients admitted to a cardiac ward died less commonly at follow-up than those treated in a general medicine ward (34% vs. 66%, p<0.001). Differences in outcome according to baseline clinical variables are shown in Table 2.


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  		Table 2 Differences in outcome according to baseline clinical variables

 
3.3. Multivariate analysis
Including all variables described in the statistics in a single multivariate model, age was found to be the only independent predictor of outcome ({chi}2 15.5, p<0.0001). After deleting age from the model, the type of ward remains the only independent predictor ({chi}2 7.9, p<0.005). After deleting age and the type of ward from the model, combined neurohumoral therapy remains as the only independent predictor of long-term survival ({chi}2 6.2, p<0.02).

3.4. Kaplan–Meier lifetime analysis
Outcome over time was significantly different, depending on age (p<0.0001) (Fig. 1a). The fact that patients were cared for in a cardiac ward improved survival significantly (p<0.0001) (Fig. 1b). There was a significant difference over time between patients who received combined neurohumoral therapy and those who did not (p<0.0001) (Fig. 1c). Elderly patients receiving no neurohumoral therapy had a significantly worse outcome than those receiving therapy (p<0.01). Elderly patients not treated in a hospital with cardiac care also had a worse outcome (p<0.001).


Figure 1
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  		Fig. 1 (a–c) Kaplan–Meyer lifetime analysis according to age, kind of hospital care and prescribed therapy. GIM=general internal medicine.

 

   4. Discussion
Top
 Abstract
 1. Introduction
 2. Methods
 3. Results
 4. Discussion
References
 
The outcome of clinical studies is not consistently implemented in clinical practice. The problems associated with such implementation need to be carefully analyzed. The present investigation was a substudy of the EuroHeart Failure Survey, which was conducted between September 1999 and May 2000, recruiting a total of more than 11,000 patients. The initial results were presented recently [2,3]. Demographic data for the 341 patients from Austria are described elsewhere; this population is representative of the European population overall [2,3]. Our data clearly show that non-prescription of medication is mainly due to three factors: age, type of hospital and contraindications. Interestingly, the first two variables are highly interdependent. As shown in the results, younger patients receive optimal therapy more often, independent of the type of hospital. Comparable to data regarding out-patient care [4], younger patients were preferably admitted to cardiac wards, which discharge patients with more therapy [5]. This increases the prescription rate in younger patients. Although proven in several studies [6,7], older patients receive significantly less therapy. Older patients were more frequently admitted to GIM wards and under-treated independent of the type of ward. This clearly shows that, although elderly heart failure patients constitute the large majority of cases, they do not receive optimal therapy even in specialized wards. Contraindications might be the third major reason for non-prescription. However, it should be noted that most contraindications (renal dysfunction and decompensation) are a consequence of heart failure. Early treatment might circumvent these problems and avoid hospitalization. Thus, contraindications result from no treatment and not vice versa. Mortality in our population was 51%. As expected, mortality increases with age. In keeping with the published literature [8], this makes age the only independent predictor of outcome among several clinical variables. More importantly, the type of hospital and treatment are important co-factors of mortality. As mentioned above, elderly patients were less commonly admitted to cardiac wards and also received less therapy. In view of the fact that, in a multivariate model, these variables are not independent, it may be assumed that these factors at least partly account for the high mortality in elder patients. As confirmed by our data, elderly patients benefit from any kind of heart failure therapy with regard to survival. Whether elderly patients especially benefit from β-blocker or combined neurohumoral therapy cannot be answered by our data, as only 7% received β-blockers and 9% combined therapy. We conclude that heart failure treatment needs to be optimized in clinical practice. Elderly patients, who account for the majority of cases, have the greatest risk of dying. Despite this fact, hospital care is inadequate and the drug prescription rate lowest in this population.


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

  1. Remme W., Swedberg K. Guidelines for the diagnosis and treatment of chronic heart failure. Eur. Heart J. (2001) 22:1527–1560.[Free Full Text]
  2. Cleland J., Swedberg K., Follath F., Komajda M., Cohen-Solal A., Aguilar J.C., et al. On behalf of the study group of diagnosis of the working group on heart failure of the European Society of Cardiology. The EuroHeart Failure Survey programme—a survey on the quality of care among patients with heart failure in Europe Part 1: patient characteristics and diagnosis. Eur. Heart J. (2003) 24:422–463.
  3. Komajda M., Follath F., Swedberg K., Cleland J., Aguilar J.C., Cohen-Solal A., et al. On behalf of the study group of diagnosis of the working group on heart failure of the European Society of Cardiology. The EuroHeart Failure Survey programme—a survey on the quality of care among patients with heart failure in Europe Part 2: treatment. Eur. Heart J. (2003) 24:464–474.[Abstract/Free Full Text]
  4. Rutten F., Grobee D., Hoes A. Differences between practitioners and cardiologists in diagnosis and management of heart failure: a survey in every day practice. Eur. J. Heart Fail. (2003) 5:337–344.[Abstract/Free Full Text]
  5. McKee S., Leslie S., LeMaitre J., Webb D., Denvir M. Management of chronic heart failure due to systolic dysfunction by cardiologist and non-cardiologist physicians. Eur. J. Heart Fail. (2003) 5:549–555.[Abstract/Free Full Text]
  6. Palazzuoli A., Bruni F., Puccetti L., Pastorelli M., Angori P., Pasqui A., et al. Effects of carvedilol on left ventricular remodeling and systolic function in elderly patients with heart failure. Eur. J. Heart Fail. (2002) 4:765–770.[Abstract/Free Full Text]
  7. Pitt B., Segal R., Martinez F., Meurers G., Cowley A.J., Thomas I., et al. Randomised trial of losartan versus captopril in patients over 65 with heart failure (evaluation of losartan in the elderly study ELITE). Lancet (1997) 349:747–752.[CrossRef][Web of Science][Medline]
  8. Rich M., McSherry F., Williford W., Yusuf S. For the digitalis investigation group effect of age on mortality, hospitalizations and response to digoxin in patients with heart failure: the DIG study. J. Am. Coll. Cardiol. (2001) 38:806–813.[Abstract/Free Full Text]

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