a Paris, France;b Zürich, Switzerland;c Göteborg, Sweden;d Kingston upon Hull, UK;e Valencia, Spain;f Clichy, France;g Berlin, Germany;h Bergamo, Italy;i Groningen, The Netherlands;j Birmingham, UK;k Warsaw, Poland;l Lisbon, Portugal;m Moscow, Russia;n Budapest, Hungary;o Prague, Czech Republic;p Department of Primary Care & General Practice, University of Birmingham, UK;q Practice, Newcastle, UK
Received September 6, 2002; accepted September 18, 2002 * Corresponding author. Michel Komajda, Institut de Cardiologie, GH Pitié-Salpêtrière, 47-83 Bld de l'Hôpital, 75013 Paris, France.
E-mail address: j.g.cleland{at}hull.ac.uk
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Abstract |
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Methods The survey screened discharge summaries of 11 304 patients over a 6-week period in 115 hospitals from 24 countries belonging to the ESC to study their medical treatment.
Results Diuretics (mainly loop diuretics) were prescribed in 86.9% followed by ACE inhibitors (61.8%), beta-blockers (36.9%), cardiac glycosides (35.7%), nitrates (32.1%), calcium channel blockers (21.2%) and spironolactone (20.5%). 44.6% of the population used four or more different drugs. Only 17.2% were under the combination of diuretic, ACE inhibitors and beta-blockers. Important local variations were found in the rate of prescription of ACE inhibitors and particularly beta-blockers. Daily dosage of ACE inhibitors and particularly of beta-blockers was on average below the recommended target dose. Modelling-analysis of the prescription of treatments indicated that the aetiology of heart failure, age, co-morbid factors and type of hospital ward influenced the rate of prescription. Age <70 years, male gender and ischaemic aetiology were associated with an increased odds ratio for receiving an ACE inhibitor. Prescription of ACE inhibitors was also greater in diabetic patients and in patients with low ejection fraction (<40%) and lower in patients with renal dysfunction. The odds ratio for receiving a beta-blocker was reduced in patients >70 years, in patients with respiratory disease and increased in cardiology wards, in ischaemic heart failure and in male subjects. Prescription of cardiac glycosides was significantly increased in patients with supraventricular tachycardia/atrial fibrillation. Finally, the rate of prescription of antithrombotic agents was increased in the presence of supraventricular arrhythmia, ischaemic heart disease, male subjects but was decreased in patients over 70.
Conclusion Our results suggest that the prescription of recommended medications including ACE inhibitors and beta-blockers remains limited and that the daily dosage remains low, particularly for beta-blockers. The survey also identifies several important factors including age, gender, type of hospital ward, co morbid factors which influence the prescription of heart failure medication at discharge.
Key Words: Heart failure Medical treatment Survey
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1. Introduction |
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2. Patients and methods |
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3. Methods |
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4. Results |
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However, patients admitted to general internal medicine wards were older (71.7% of patients were aged 70 years compared to 46.8% on cardiology wards, 25.1% difference, 95% CI 23 to 27%) and had more co-morbidity (83.8 vs 73.8% of patients, 10% difference, 95% CI 8 to 12%).
ACE inhibitors and beta-blockers were prescribed more commonly in younger patients (67.7% of those aged <70 years vs 57.9% of those aged 70 years for ACE inhibitors, odds ratio 1.3, 95% CI 1.18 to 1.43); 47.4 of those aged <70 years vs 30% of those aged
70 years for beta-blockers, odds ratio 1.82, 95% CI 1.63 to 2.04.
The presence of ischaemic heart disease defined by current/previous myocardial infarction or angina was associated with a higher rate of prescription of beta-blockers (42.1% with vs 22.9% without IHD, odds ratio 2.63, 95% CI 2.32 to 2.99) and calcium channel blockers (25% with vs 11% without IHD, odds ratio 2.56, 95% CI 2.22 to 2.95). Similarly, the presence of a history of hypertension was associated with a higher rate of prescription of ACE inhibitors (69.2% with vs 53.4% without, ) and beta-blockers (40.5% with vs 32.7% without,
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4.3. Role of co-morbidity
The presence of co-morbidity had a powerful influence on the rate of prescription of heart failure medications. Beta-blockers were prescribed only to 19.1% of patients with a history of asthma or pulmonary disease as compared to 43.2% to patients without pulmonary disease, odds ratio 0.35, 95% CI 0.30 to 0.40. Renal dysfunction defined by a serum creatinine of 176µmoll1(2mgdl1) influenced the rate of prescription of ACE inhibitors (57% in patients with vs 66.3% in patients without renal dysfunction) 9.2% difference, 95% CI 4 to 14% (Table 6). There was no obvious difference in the average daily dosage of the most commonly prescribed ACE inhibitors according to renal function (Table 7). Renal dysfunction also influenced the rate of prescription of spironolactone (15.6% with vs 22% without, difference, 6.4, 95% CI 10 to 2%). However, the effect of renal dysfunction on the use of ACE inhibitors and spironolactone disappeared in a multivariate analysis (see below) suggesting that other factors associated with renal dysfunction may have had an important effect on prescribing patterns.
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Antithrombotic therapy, either an antiplatelet or anticoagulant agent, was used in 77.6% of the patients (ranging from 57.7 to 92.7% in different countries). The rate of prescription was influenced by the presence of atrial fibrillation/supraventricular tachycardia (82.7 with vs 74% without, odds ratio 2.86, 95% CI 2.41 to 3.39) and the presence of ischaemic heart disease (82.3 with vs 65.2% without, odds ratio 2.96, 95% CI 2.51 to 3.50). The average daily dosage of aspirin was 114±57mg.
Anticoagulant therapy was more likely to be prescribed in the presence of AF/SVT (59.4%) than in the absence of arrhythmia (33.4%, 22% difference, 95% CI 20 to 24%).
Digitalis glycosides were more likely to be used in the presence of atrial fibrillation or supraventricular tachycardia (56.2 with vs 20.9% without, odds ratio 5.50, 95% CI 5.02 to 6.03).
4.4. Multivariate analysis (Table 8)
4.4.1. Beta-blockers
In a multivariate model, the odds of the patient receiving a beta-blocker were increased if the admission was to a cardiology ward rather than a general ward (odds ratio 2.69, 95% CI 1.05 to 1.29) and were also independently increased for patients suffering from ischaemic heart disease (odds ratio 2.63, 95% CI 2.32 to 2.99). Odds were decreased in the presence of respiratory/pulmonary disease (odds ratio 0.35, 95% CI 0.30 to 0.40) and for patients aged 70 (odds ratio 0.55, 95% CI 0.49 to 0.61).
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4.4.3. Spironolactone
In a multivariate model, the odds of the patient receiving spironolactone were increased if the admission was to a cardiology ward rather than a general ward (odds ratio 1.61, 95% CI 1.31 to 1.99), for male patients compared with female patients (odds ratio 1.28, 95% CI 1.15 to 1.43) and were also independently increased for patients suffering from supraventricular tachycardia or arrhythmia (odds ratio 1.39, 95% CI 1.25 to 1.56). Odds were decreased in the presence of ischaemic heart disease (odds ratio 0.78, 95% CI 0.66 to 0.92), for patients aged 70 and over (odds ratio 0.76, 95% CI 0.67 to 0.85) and for those who had suffered a stroke.
Patients with ischaemic heart disease who had been admitted to cardiology wards were less likely to receive spironolactone (odds ratio 0.68, 95% CI 0.54 to 0.87) but more likely to receive spironolactone if they had also had a stroke (odds ratio 5.31, 95% CI 1.13 to 25.05).
4.4.4. Calcium channel blockers
Men were less likely than women to receive calcium channel blockers (odds ratio 0.79, 95% CI 0.71 to 0.88) and the odds were also reduced for patients admitted to cardiology wards rather than general internal medicine wards (odds ratio 0.88, 95% CI 0.78 to 0.99). The odds of receiving calcium channel blockers were independently increased for patients with ischaemic heart disease (odds ratio 2.56, 95% CI 2.22 to 2.95).
4.4.5. Antithrombotics and aspirin
The odds of a patient receiving an antithrombotic agent (including aspirin) were increased by the presence of SVT/AF (odds ratio 2.86, 95% CI 2.41 to 3.39) and by the presence of ischaemic heart disease (odds ratio 2.96, 95% CI 2.51 to 3.50). The odds for male patients were independently higher than for female patients (odds ratio 1.19, 95% CI 1.00 to 1.40) but were decreased for patients over the age of 70 (odds ratio 0.80, 95% CI 0.72 to 0.89). Men with ischaemic heart disease were more likely to receive an antithrombotic agent (odds ratio 1.37, 95% CI 1.12 to 1.69). Patients with ischaemic heart disease were less likely to receive antithrombotic therapy if they also had SVT/AF (odds ratio 0.52, 95% CI 0.42 to 0.64) (Table 8).
An analysis of factors predicting treatment with aspirin showed that odds were increased for patients aged over 70 years (odds ratio 1.92, 95% CI 1.57 to 2.34) and for male patients (odds ratio 1.34, 95% CI 1.23 to 1.46). Patients with ischaemic heart disease had higher odds of receiving aspirin (odds ratio 5.67, 95% CI 4.78 to 6.72) especially if they were men (odds ratio 1.66, 95% CI 1.39 to 1.99). The presence of SVT/AF reduced the odds of treatment with aspirin both in isolation (odds ratio 0.44, 95% CI 0.38 to 0.51) and further in combination with ischaemic heart disease (odds ratio 0.44, 95% CI 0.36 to 0.54.
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5. Discussion |
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In the EPICAL study, which gathered information on hospitalization in patients with severe heart failure due to left ventricular systolic dysfunction during 1995 in Eastern France, 75% of patients were receiving ACE inhibitors but only 5% beta-blockers at discharge.10 The patient population was younger than patients enrolled in our survey and consisted mainly of males. The IMPROVEMENT of Heart Failure survey enrolled >10 000 patients in primary care in 14 European countries during 1999. The composition of this population, in terms of age, gender, and left ventricular systolic dysfunction, was remarkably similar to the current survey, reflecting the high rates of hospitalization amongst patients with heart failure. In the IMPROVEMENT survey, 60% of patients were prescribed an ACE inhibitor, 30% a beta-blocker and 12% spironolactone.11 In a large survey of patients hospitalized for chronic heart failure in cardiology, general medicine and geriatric departments in France, only 49 and 11% of patients received an ACE inhibitor and a beta-blocker respectively on admission.4 Similar trends were found in two recent surveys in Australia and France.5,12 In the Australian study, 58.1% of patients only were receiving ACE inhibitors and 12% beta-blockers. In the French survey performed among ambulatory patients in private practice, the respective numbers were 54 and 11%. However, most of these surveys included relatively small numbers of patients (5001000) and were performed on a national basis. The Euro Heart Survey on heart failure is the first pan-European Survey in hospitalized patients.
Diuretics and particularly loop diuretics were by far the most commonly used heart failure medications in this survey. Although entry criteria may have influenced the results, our findings are in agreement with previous surveys.46,12 There was little variation from one centre to the other in the rate of prescription of diuretics. This finding contrasts with the important variations found in the rate of prescription of both ACE inhibitors and beta-blockers. However, it should be emphasized that these variations are individual centre variations and therefore only partly reflect the current situation in ordinary practice in a given country. It is likely that variation between centres within each country are also large.
The rate of prescription of ACE inhibitors reached 80% in patients with documented reduction in ejection fraction, which indicates that the situation is improving as compared to previous surveys. In contrast, beta-blockers were clearly under-prescribed even in patients with a documented low ejection fraction.
Various factors can explain the under use of ACE inhibitors and beta-blockers:
Treatment directed at ischaemic heart disease, rather than at heart failure, probably explains why the prescription of beta-blockers was not even lower and also explains the high rate of use of calcium channel blockers and nitrates, agents for which there is little evidence of benefit in patients with left ventricular systolic dysfunction. Spironolactone was prescribed in more than 20% of our overall population and even more commonly in the absence of renal dysfunction, suggesting that the conclusions of the RALES study have been accepted in Europe.17 Angiotensin II receptor antagonists were used only in a minority of patients, reflecting uncertainty over the role of these agents as an alternative or in addition to ACE inhibitors.18,19 ESC guidelines do not advise the use of this class of drugs as first line therapy.
Cardiac glycosides, an old fashioned heart failure medication which has only been demonstrated to reduce the rate of hospitalizations for patients in sinus rhythm20 but which may continue to have a role for patients with atrial fibrillation was still used in about a third of our population, including 21% of those without supraventricular arrhythmia. In most ESC countries, more patients with heart failure now receive beta-blockers than receive digoxin.
5.2. Dosage and preparations
Daily dosage of diuretics varied considerably but many patients received high doses suggesting that many had advanced heart failure.
The most commonly prescribed ACE inhibitors were used at doses equal to or greater than 50% of the doses used in randomized trials except for captopril, which was used in doses substantially lower than target. This suggests that guideline recommendations are being followed in great part. Since we did not record the reason for using a given dosage of a drug, we are unable to assess whether dosing was limited for reasons of safety or tolerance or because of lack of attention by the physician. Our patients were, on average, considerably older than the patients in the clinical trials. Most ACE inhibitors are eliminated mainly be the kidneys and lower doses may be justified in elderly patients as they have reduced renal clearance. Although the ATLAS trial showed that higher doses of an ACE inhibitor, lisinopril, were associated with some improvement in morbidity21 there is no robust evidence that high doses of ACE inhibitor are of benefit to very elderly patients (aged >75 years) with heart failure.
On average, daily dosage of beta-blockers were far below the target doses used in randomized trials. It is possible that many patients were still in the process of having the dose of beta-blocker uptitrated but it is also probably reflects caution on the part of clinicians and the absence of a substantial dose-ranging study to show the relative benefits and problems of titrating to higher doses. Atenolol, for which no substantial trial in heart failure exists22 and which does not have a license for this indication, constituted nearly 25% of all beta-blockers prescribed, the choice of this agent probably reflecting its use to treat underlying problems, such as ischaemic heart disease or hypertension.
Overall, our results suggest that the application of modern therapeutic guidelines has improved compared to that previously reported in smaller national surveys.
5.3. Limitations
We acknowledge that Euro Heart Survey on Heart Failure was concentrated on University hospitals clustered with one or more community hospitals. This design might have resulted in an over representation of metropolitan hospitals vs rural healthcare units. Therefore, the Euro Heart Survey on Heart Failure is not a true epidemiological survey representative of the overall population but rather a large hospital-based European data base.
5.4. In summary
We report here the detailed analysis of treatments used in the Euro Heart Survey on Heart Failure. Diuretics were the most commonly prescribed class of agent. Overall, ACE inhibitors were used in 61% of patients and almost 80% of those with reduced left ventricular ejection fraction. The respective figures for beta-blockers were less widely used overall (37%) and in patients with reduced left ventricular ejection fraction (49%). Daily dosages of ACE inhibitors reached 5060% of the target recommended dose except for captopril, which was prescribed at much lower doses, whereas the daily dosage of beta-blockers were far below the target dose used in randomized trials.
Many factors including age, aetiology of heart failure, co-morbidity, specialty at discharge and pathophysiology of heart failure influenced the rate of prescription of the recommended drugs. Overall, our results suggest that the situation is improving for ACE-inhibitor prescription but remains suboptimal for beta-blockers. Continued medical education and improved organisation of services are required to improve the dissemination and uptake of guidelines on treatment of chronic heart failure in daily practice.
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