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European Journal of Heart Failure 2001 3(2):249-255; doi:10.1016/S1388-9842(00)00144-6
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© 2001 European Society of Cardiology

Poles apart, but are they the same? A comparative study of Australian and Scottish patients with chronic heart failure

Simon Stewarta,b, Lynda Blueb, Simon Capewellc, John D. Horowitza and John J. McMurrayb,*

a Department of Cardiology, The Queen Elizabeth Hospital / University of Adelaide Adelaide, Australia
b CRI in Heart Failure, Wolfson Building, University of Glasgow Glasgow G12 8QQ, Scotland, UK
c Department of Public Health, University of Glasgow Glasgow, Scotland, UK

* Corresponding author. Tel./fax: +44-141-330-6588. E-mail address: j.mcmurray{at}bio.gla.ac.uk (J.J. McMurray).


   Abstract
Top
 Abstract
1. Introduction
 2. Methods
 3. Results
 4. Discussion
 References
 
This paper reports on an international comparison of the characteristics, treatment and health outcomes of chronic heart failure (CHF) patients discharged from acute hospital care in Australia and Scotland. The baseline characteristics and treatment of 200 CHF patients recruited to a randomised study of a non-pharmacological intervention in Australia and 157 CHF patients concurrently recruited to a similar study in Scotland were compared. Subsequent health outcomes (including survival and readmission) within 3 months of discharge in those patients who received usual post-discharge care in Australia (n = 100) and Scotland (n = 75) were also compared. Individuals in both countries were predominantly old and frail with significant comorbidity likely to complicate treatment. Similar proportions of Australian and Scottish patients were prescribed either a ‘high’ (20 vs. 18%) or medium (64 vs. 66%) dose of an angiotensin-converting enzyme inhibitor. Proportionately more Australian patients were prescribed a long-acting nitrate, digoxin and/or a β-blocker. At 3 months post-discharge, 57 of the 100 (57%: 95% CI 47–67%) Australian and 37 of the 75 (49%: 95% CI 38–61%) Scottish patients assigned to ‘usual care’ remained event-free (NS). Similarly, 15 vs. 12% required ≥ 2 unplanned readmission (NS) and 16 vs. 19% of Australian and Scottish patients, respectively, died (NS). Australian and Scottish patients accumulated a median of 0.6 vs. 0.9 days, respectively, of hospitalisation/patient/month (NS). On multivariate analysis (including country of origin), unplanned readmission or death was independently correlated with severe renal impairment (adjusted odds ratio 4.4, P < 0.05), a previous hospitalisation for CHF (2.3, P < 0.05), longer index hospitalisation (2.7 for > 10 days, P < 0.05) and greater comorbidity (1.3 for each incremental unit of the Charlson Index, P = 0.05). Health outcomes among predominantly old and frail CHF patients appear to be independent of the health-care system in which the patient is managed and more likely to be dependent on the syndrome itself.

Key Words: Chronic heart failure • Pharmacology • Hospitalisation • Mortality

Received June 26, 2000; Revised September 6, 2000; Accepted November 3, 2000


   1. Introduction
Top
 Abstract
 1. Introduction
2. Methods
 3. Results
 4. Discussion
 References
 
Recent reports from large clinical trials and registries have shown considerable international variation in the use of particular medications for chronic heart failure (CHF) [1–3]. There is, however, no international comparison of outcomes in CHF patients not participating in clinical trials. We do not know, for example, whether the reported differences in treatment affect outcome or whether different health care systems have an influence on hospitalisation rates, independently of the syndrome of CHF itself. Furthermore, the large clinical trials, to date, have recruited subjects unrepresentative of CHF patients in general. The elderly and women have, in particular, been excluded [4].

Recently, two trials of specialist nurse intervention in CHF have beer conducted in Adelaide, Australia [5] and Glasgow, Scotland [6]. The design of these studies was very similar, thus allowing comparison between the baseline characteristics and subsequent health outcomes of participating patients. These two studies also enrolled a much broader range of patients than usually recruited in CHF trials. It is also possible to compare the Australian and Scottish studies to a similar one carried out by Rich and colleagues in the United States of America [7]. We have taken the opportunity offered by these recent developments to compare, for the first time, the characteristics and outcomes in hospitalised CHF patients in two different countries.


   2. Methods
Top
 Abstract
 1. Introduction
 2. Methods
3. Results
 4. Discussion
 References
 
2.1. Location of participants
Both controlled studies of specialist nurse intervention in CHF commenced recruitment in their respective countries in March 1997 and enrolled patients until the latter half of 1999. The relevant institution's ethics committee approved each study and all study patients consented to participate. As such, both studies conformed to the principles outlined in the Declaration of Helsinki. In Australia, a total of 205 patients were recruited from the north-west region of Adelaide, a metropolitan area with a disproportionate number of elderly and socially disadvantaged persons and higher admission rates per capita for the region [8]. All patients were admitted to The Queen Elizabeth Hospital, a tertiary referral hospital servicing the area. A total of 200 patients was subsequently discharged alive and randomised to either usual care (n=100) or the study intervention (n=100). Similarly, 165 Scottish patients were recruited from the northwest sector of the city of Glasgow; likewise, a metropolitan region with a disproportionate number of elderly and socially disadvantaged persons and higher admission rates compared to the overall population [9]. All patients were admitted to The Western Infirmary, a tertiary referral hospital servicing the area. A total of 158 patients were discharged alive and randomised to either usual care (n=75) or the study intervention (n=83).

2.2. Patient characteristics
Both studies required patients to have a diagnosis of CHF with documented left ventricular systolic dysfunction and an associated hospitalisation where CHF was the primary cause. In the Scottish study, the index admission represented the qualifying CHF-related hospitalisation. In the Australian study, the qualifying hospitalisation may have occurred previously. In both studies, patients were discharged home and resided within the hospital's catchment area.

Both studies had minimal exclusion criteria. Neither had upper age limits (although the study in Adelaide required patients to be aged ≥55 years), nor excluded patients on the basis of comorbidity. However, patients were excluded on the basis of reversible ischaemia precipitating their qualifying hospitalisation, valvular heart disease amenable to surgical correction, intended cardiac transplantation and presence of non-cardiac, terminal disease.

There were some differences between the two cohorts. Patients recruited into the Scottish study were admitted to hospital under the care of a general physician, whilst all patients recruited in Australia were admitted under the care of a cardiologist. Moreover, in the Scottish study, left ventricular systolic dysfunction was defined on a semi-quantitative scoring system of the patient's echocardiogram with a requirement for at least ‘mild’ dysfunction to be evident. In Australia, a similar, but more quantitative, criteria of a documented LVEF of ≤55% was required for study entry.

2.3. Usual after discharge care
Neither study limited extent of in-hospital or post-discharge care. In Australia, patients were reviewed at regular intervals by both their general practitioner and cardiologist. In Scotland, patients were followed-up by their general practitioner and cardiologist or general physician.

2.4. Study follow-up
All Australian and Scottish patients in these two studies were followed-up for at least 3 months post-discharge. Data collected from both studies permitted estimation of event-free survival (unplanned readmission or out-of-hospital death) number and frequency of unplanned readmissions, associated hospital stay and overall survival.

2.5. Statistical analysis
Univariate comparison of the baseline characteristics of the two cohorts (a total of 375 patients) and subsequent health outcomes among patients assigned to ‘usual care’ (a total of 175 patients) involved utilisation of the following: {chi}2 analysis (with calculation of odds ratio [OR] and 95% confidence intervals [CI]) for discrete variables, the student's t-test for normally distributed continuous variables and the Mann–Whitney test for non-normally distributed continuous variables. Kaplan–Meir survival curves were constructed for time-dependent variables and analysed with both the log-rank and the Breslow tests to detect differences in both the number and timing of events. Multiple logistical regression, using entry of variables at a significance level of 0.2 from univariate analysis, and step-wise rejection of variables at the 0.05 level of significance, was used to identify independent predictors of death or readmission. All analyses were performed using SPSS for Windows (9.0).


   3. Results
Top
 Abstract
 1. Introduction
 2. Methods
 3. Results
4. Discussion
 References
 
3.1. Baseline characteristics
Analysis of the baseline demographic and clinical characteristics of the two groups revealed that these were predominantly old and frail patients with significant comorbidity likely to complicate treatment (Table 1). The age and gender distributions of the two cohorts were almost identical. There were some notable differences between the two groups, however. For example, significantly more Scottish patients lived alone, were admitted with acute pulmonary oedema and were assessed to be dependent for at least one activity of daily living at hospital discharge. Scottish patients were also hospitalised, on average, 2 days longer than their Australian counterparts. Conversely, Australian patients were more likely to come from a non-English speaking background, have been previously treated and hospitalised for CHF. They also had on average greater renal dysfunction and more comorbidity overall (e.g. chronic angina pectoris and diabetes).


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  		Table 1 Baseline demographic and clinical characteristics of Australian and Scottish patients at the time of hospital dischargea

 
3.2. Prescribed pharmacotherapy
Consistent with their greater overall burden of disease, Australian patients were prescribed more extensive pharmacotherapy. However, in both countries the majority of patients were prescribed a diuretic (n=338). The principle drug of choice in this respect was frusemide (93%); a median total daily dose of 80 mg (IQR 40, 120 mg) being prescribed in both countries. Overall, 36 and 32% of Australian and Scottish patients, respectively, were prescribed what is usually considered a high daily dose of frusemide (>120 mg) [1].

Whilst the majority of patients in both countries were prescribed an angiotensin-converting enzyme (ACE) inhibitor, the agents of choice and dosages in which they were prescribed were different. In Scotland, the most commonly prescribed agents were enalapril (45%) and lisinopril (32%) in a mean total daily dose of 20±12 and 15±5 mg, respectively. In Australia, the most commonly prescribed agents were captopril (40%) and enalapril (35%) in a mean total daily dose of 73±43 and 11±5 mg, respectively. Overall, however, a similar proportion of patients in Australia and Scotland were prescribed what are usually considered to be ‘high’ (75–150 mg captopril, 21–40 mg enalapril/lisinopril or equivalent) 20 vs. 18%; ‘medium’ (25–50 mg captopril, 10–20 mg enalapril or lisinopril, or equivalent) 64 vs. 66%; or ‘low’ (<25 mg captopril, <10 mg enalapril or lisinopril or equivalent) 16% at both centres, doses of ACE inhibition [1].

The two cohorts were somewhat different with respect to prescribed long-acting nitrate, digoxin and β-adrenoceptor antagonist therapy, with the Adelaide cohort receiving significantly more of these agents. As with ACE inhibitors, however, prescribed dosages were similar when used. For example, the prescribed mean daily dose of digoxin among the Australian and Scottish cohorts was 114±80 vs. 111±59 µg, respectively.

3.3. Health outcomes
Overall, 49% (95% CI 38–61%) of Scottish patients remained ‘event-free’ within 3 months compared to 55% (95% CI 45–65%) in Australia. Fig. 1 represents the probability of event-free survival (unplanned readmission or out-of-hospital death) during this period. As such, the two event curves were similar for the two cohorts (P=0.76: log-rank test).


Figure 1
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  		Fig. 1 Probability of event-free survival within 3 months of discharge from hospital in Australian (n=100) and Scottish (n=75) patients subject to usual care. No significant difference between groups in respect to the number and timing of events according to the log-rank and Breslow tests.

 
In Australia, the 100 ‘usual care’ patients accumulated a total of 30 unplanned readmissions compared to the 43 readmissions accumulated by the 75 ‘usual care; patients in Scotland (P<0.01). However, a similar proportion of Australian and Scottish patients, 15 (95% CI 9–24%) and 12% (95% CI 6–22%), respectively, accumulated ≥2 unplanned readmissions during this period (NS). Therefore, the difference in the total number of unplanned readmissions was largely caused by a small number of Scottish patients being repeatedly readmitted during this period. Despite the disparity in hospital events, there was no significant difference between the two study cohorts with respect to days of hospitalisation, with Australian and Scottish patients accumulating a median of 0.6 vs. 0.9 days, respectively, of hospitalisation/patient/ month (NS).

Survival was also similar in the two cohorts, with 19 (95% CI 11–29%) vs. 16% (95% CI 9–25%) of Scottish and Australian patients dying within 3 months of discharge, respectively. Fig. 2 represents the survival curves for the two cohorts which, like those for event-free survival, are similar (P=0.69; log-rank test).


Figure 2
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  		Fig. 2 Probability of survival within 3 months of discharge from hospital in Australian (n=100) and Scottish (n=75) patients subject to usual care. No significant difference between groups in respect to the number and timing of events according to the log-rank and Breslow tests.

 
According to the initial univariate analysis, the following were associated with an increased probability of unplanned readmission or death within 3 months — greater comorbidity (higher Charlson index score [10]); a previous hospitalisation for CHF; hypertension; atrial fibrillation; anaemia; absence of an ACE inhibitor; higher NYHA classification; greater number of prescribed medications; presence of severe renal function impairment; and longer length of stay.

On subsequent multivariate analysis, severe renal function impairment, a previous hospitalisation for CHF, longer index hospitalisation and a higher Charlson index of comorbidity score were found to be significant independent predictors in this regard (refer to Table 2). Although not retained in the final model, atrial fibrillation was also associated with a strong probability of readmission or death (adjusted OR 2.2, 95% CI 0.92, 5.2; P=0.08).


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  		Table 2 Independent correlates of event-free survival within 3 months of hospital discharge in Australian and Scottish CHF patients subject to usual care (n=175)a

 

   4. Discussion
Top
 Abstract
 1. Introduction
 2. Methods
 3. Results
 4. Discussion
References
 
This study represents the first detailed comparison of the clinical characteristics and health outcomes of older, and therefore more representative, CHF patients requiring acute hospitalisation in two different countries. It suggests that CHF patients admitted to a tertiary referral hospital servicing an urban population in Glasgow, Scotland [6] are remarkably similar to those admitted to a comparable institution in Adelaide, Australia [5]. Unlike the majority of clinical trials [4], the study cohorts were older and included a large proportion of women. Consistent with previous reports [11,12], many patients had at least one non-cardiac condition likely to complicate treatment and adversely affect their health.

There were some differences in the baseline characteristics and prescribed treatment of the two cohorts. Overall, the Australian cohort had more comorbidity and had been treated for CHF over a longer period. Consistent with a recent report of treatment practices among the different countries participating in the PRIME-II [1] and CHARM studies [13], the use of digoxin in Scotland was low compared to that in Australia. However, proportionately more Australian patients were eligible for digoxin therapy [14], due to prior hospitalisation for CHF. More Australian patients were also prescribed a β-adrenoceptor antagonist. This, once again, may reflect their more extensive CHF history, or because of their treatment by cardiologists who have been shown to be more up-to-date with the current literature and guidelines [15,16]. Conversely, Scottish patients were, on average, admitted for 2 days longer than their Australian counterparts during their index hospitalisation.

Despite these differences, the health outcomes independently observed in CHF patients either living in the Southern or Northern Hemisphere were similar. Although the observed similarities may simply reflect pure serendipity, the observed outcomes are consistent with those emanating from other developed countries. For example, in a comparable study of specialist nurse intervention by Rich and colleagues in the United States, the number of reported ‘usual care’ patients (n=140) who remained event-free at 3 months was 54% (95% CI 46–63%), 16% (95% CI 10–23%) required two or more readmissions, and 12% (95% CI 7–19%) died [7]. Although the mortality rate was lower in this particular cohort, this most probably reflects the fact that fewer patients with left ventricular systolic dysfunction were recruited: its presence usually being a major determinant of survival [17], but not morbidity [18]. Moreover, the 6–12-month mortality and morbidity rates observed in these two cohorts (data not shown) are consistent with recent large-scale reports from a number of developed countries (including Scotland), which suggest that approximately 50% of HF patients are readmitted within 6 months and 33% die within 12 months of acute hospitalisation [19–22].

The sub-optimal use of proven pharmacological agents (particularly ACE inhibitors) is one possible reason for the consistently high morbidity and mortality rates among patients admitted with CHF [23]. During the period of study, however, the majority of patients were receiving appropriate pharmacotherapy. The incremental benefits of nurse-led programs in reducing readmissions and prolonging event-free survival among such CHF patients [5–7,24,25] supports the supposition that a multitude of factors [26], including treatment non-adherence [27] and sub-optimal self-care behaviour patterns overall [28], contribute to consistently high morbidity and mortality rates.

Pooled multivariate analysis of possible demographic and clinical determinants of event-free survival within 3 months of hospital discharge suggested that the health-care system in which the patients were managed had little influence on outcome. Consistent with previous studies, concurrent renal failure (especially when resulting in intolerance to ACE inhibitors) [12,29], a history of previous or prior admissions for HF, extended length of stay and a higher comorbid burden were all independently associated with a worse health outcome.

Any interpretation of these data needs to consider a number of study limitations, including the fact that this was not a prospective study with formal power calculations to determine any observed differences. Despite fairly broad inclusion and minimal exclusion criteria, both studies introduced some selection bias. For example, CHF patients with ‘diastolic’ left ventricular dysfunction are undoubtedly under-represented. Moreover, both studies selected patients from urban, largely disadvantaged populations admitted to tertiary affiliated hospitals and represent only moderately sized cohorts. Furthermore, we were unable to completely match all baseline and outcome data for univariate and multivariate comparisons.

This study, however, represents the first detailed examination of the characteristics and subsequent health outcomes of CHF patients admitted to hospital in two different countries. Although these data need to be confirmed in larger cohorts and in a more systematic way, they suggest that, irrespective of the health care system, it is the syndrome of CHF and the inherent problems it engenders for the individual that largely determines health outcomes.


   Acknowledgements
 
We gratefully acknowledge the invaluable contribution of Caroline Round from the Robertson Centre for Biostatistics at the University of Glasgow. The Scottish study was supported by a grant from the Scottish Health Office. Simon Stewart is supported by a National Heart Foundation of Australia Overseas Postdoctoral Research Fellowship.


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

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