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European Journal of Heart Failure 2000 2(2):201-207; doi:10.1016/S1388-9842(00)00071-4
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© 2000 European Society of Cardiology

Angiotensin converting enzyme (ACE) inhibitors in the treatment of heart failure in general practice in north Cumbria

Martin Toala,*,1 and Robert Walkerb

a 10 Larchmoor Park, Gerrards Cross Road, Stoke Poges, Bucks SL2 4EY, UK
b North Cumbria Health Authority Wavell Drive, Carlisle CA1 2SE, UK

* Corresponding author. Tel.: +44-1753-662198. E-mail address: martin.toal{at}virgin.net (M. Toal).


   Abstract
Top
 Notes
 Abstract
1. Introduction
 2. Method
 3. Results
 4. Discussion
 References
 
Background: A great deal of research has demonstrated the benefits of treating patients with chronic heart failure with Angiotensin Converting Enzyme (ACE) inhibitors. There is rather less research on the actual uptake of treatment in general practice, and in particular methods that might improve that uptake.

Aim: To study the attitudes and practice of medical practitioners in North Cumbria in the treatment of heart failure.

Method: Semi-structured interviews with 16 general practitioners and nine hospital physicians in the Carlisle area and an audit of general practice case notes.

Results: Two hundred and fifty-eight patients were identified with heart failure. Prevalence was 1.1%. Fifty percent were on an ACE inhibitor, the mean dose of which was less than half the typical research dose. Patients who had an echocardiogram were much more likely to be on an ACE inhibitor. General practitioners were enthusiastic to use ACE inhibitors, but felt that greater access to echocardiography was required. Hospital physicians were happy to improve access within an agreed protocol.

Conclusion: Improved uptake of ACE inhibitors could be assisted by the development of a protocol for investigation and treatment. This protocol should be evidence-based and agreed between local GPs, hospital physicians and the Health Authority.

Key Words: Heart failure • Echocardiography • Morbidity

Received December 14, 1999; Revised February 25, 2000; Accepted March 6, 2000


   1. Introduction
Top
 Notes
 Abstract
 1. Introduction
2. Method
 3. Results
 4. Discussion
 References
 
Chronic heart failure is a condition with a poor prognosis [1]. It mainly affects older people, and prevalence doubles with each decade of age [2]. Heart failure causes 5% of all admissions to hospital and costs the National Health Service some £360 000 000/year at 1990 prices [3]. Good evidence exists to show the benefits of ACE inhibitors on morbidity and mortality for patients with mild, moderate or severe heart failure [4–6], after myocardial infarction [7,8] and in the pre-symptomatic stage [9]. There is little such evidence for diuretics [10]. Research in general practice has shown that only a minority of patients with heart failure receive treatment with ACE inhibitors, with mean doses usually much lower than recommended research doses [11]. Impediments to greater usage are not fully understood, although concern over side effects may be at least partly responsible [12]. Doctors observe cough as a common side effect in their patients and for this problem angiotensin II blockers may be better tolerated [13]. Echocardiography is a cost-effective investigation for identifying left ventricular dysfunction associated with heart failure, but a minority of patients receive this investigation [14]. Trials of open access echocardiography in several parts of the UK have shown it to improve uptake of ACE inhibitors [15,16].


   2. Method
Top
 Notes
 Abstract
 1. Introduction
 2. Method
3. Results
 4. Discussion
 References
 
Three general practices in north Cumbria were selected to represent a mixture of practice size, location and fundholding status. The practices had 16 principals or assistants in general practice and two GP registrars between them, and a total patient population of 23 210 patients. Practice characteristics are shown in Table 1.


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  		Table 1 Practice characteristics

 
Each practice allowed one of the authors (MT) to perform an audit of case records and a set of interviews with the doctors. The audit method has been previously used in studies in general practice [17,18], and was used because in general practice decisions for initiation of ACE inhibitors often rely on scrutiny of case records. The audit method assumed that any patient known to have symptoms of heart failure would be receiving a loop diuretic or ACE inhibitor. The repeat prescription systems in the practices were searched for all repeat prescriptions for these drugs. However, clearly many patients on a diuretic or ACE inhibitor are being treated for other conditions, such as hypertension. Therefore, after this initial trawl, the case records were then examined to determine if a case definition for heart failure could be fulfilled. Patients on neither a diuretic nor an ACE inhibitor would not be identified by this method.

The case definition used was previously used in other studies in general practice. That definition was:

One or more of:

  1. Pulmonary oedema confirmed radiologically or clinically.
  2. Peripheral oedema and a raised jugular venous pressure.
  3. Evidence of heart disease (electrocardiographic, echocardiographic or clinical) where symptoms of dyspnoea improved on taking anti-failure medication and relapsed on discontinuation.

The case record often included hospital records (discharge letters, investigations and out-patient visits). As in previous studies these hospital records were used when available. The hospital was not contacted for additional information, as this would not usually be done prior to a decision to initiate ACE inhibitors.

Patients thus identified were deemed to be a case. The method did not allow patients with isolated diastolic heart failure to be identified from within this population.

Practice B required a different methodology because of the different recording system used. That practice no longer maintained paper records, instead entering all diagnoses and investigations on computer using the OXMISS system. Symptoms were not recorded in the records. The coded diagnosis was therefore used to estimate prevalence in that practice and a trawl was not required. For all three practices, patient demographics, details of diuretic and ACE inhibitor medication, recorded investigations (including echocardiography), as well as other relevant medical conditions were noted.

Interviews with the doctors were conducted using the semi-structured interview schedule. Each interview took approximately 30 min and doctors were encouraged to elaborate on answers and make additional points as they deemed appropriate. Two interviews were not completed in time for inclusion in the final report.

Nine interviews using an altered interview schedule were carried out with the consultant physicians in the local district general hospital. These nine physicians comprised the entire medical consultant staff and included two cardiologists, two nephrologists and two geriatricians. All nine consultants were involved in the care of heart failure patients.

The views expressed by the doctors were not compared with another group of practitioners, for example to try to identify if the issues identified were peculiar to this area.


   3. Results
Top
 Notes
 Abstract
 1. Introduction
 2. Method
 3. Results
4. Discussion
 References
 
3.1. Prevalence
Two hundred and fifty-nine patients were determined to fulfil the case definition for heart failure. This was a prevalence of 1.1% [95% Confidence Interval (CI) 1.0%, 1.2%]. Excluding practice B, in which the case definition could not be applied, reduced the prevalence to 1.0% (95% CI 0.8%, 1.1%). Across all three practices prevalence in patients under 65 years of age was 0.2% (95% CI 0.1%, 0.2%) and 5.4% (95% CI 4.7%, 6.1%) in patients 65 years of age or greater. This is a 27-fold difference. There were more cases in females with an overall prevalence in females of 1.2% (95% CI 1.0%, 1.4%) and a prevalence in males of 1.0% (95% CI 0.8%, 1.2%).

3.2. Standardised prevalence
The prevalence of heart failure is known to be very age sensitive, so a standardised prevalence was estimated for the European Standard Population (Table 8) using the age-specific rates obtained in the audit.

The prevalence in this standardised population was 0.71%. This population is a younger population than the study population, with a relative deficit of young people and a corresponding excess of older people in the age groups in which most cases occur. For example, 40% of cases occurred in the 75–84 years age group. In the study age group there were 97% more persons than would have been expected from the standard population. Therefore, the prevalence might be expected to be lower in the standard population.

A standardised prevalence using the European Standard Population was calculated using the practice population data in the Mair [17] paper. This gave a prevalence of 1.15%. Data in the Parameshwar [18] paper was insufficient to permit calculation of a standardised prevalence.

3.3. Aetiology
From a study of this nature, it is difficult to ascribe causation to a diagnosis of heart failure. There was evidence of ischaemic heart disease (myocardial infarction or angina pectoris) in 62% of case records, hypertension (defined as BP of 160/95 or higher) in 26%, atrial fibrillation in 23%, and valve disease in 15%.

3.4. Echocardiography
Of 259 patients with a diagnosis of heart failure, 61 (24%) had evidence of an echocardiogram in their notes. Thirty-three (54%) of these had left ventricular dysfunction of whom 29 (88%) were on an ACE inhibitor. An additional 15 patients in whom there was no left ventricular dysfunction remained on an ACE inhibitor. Of 198 patients who had not had an echocardiogram, 87 (44%) were on an ACE inhibitor. Results are summarised in Table 2.


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  		Table 2 Echocardiograms

 
3.5. Drug treatments
Most patients were on a loop diuretic. In most cases, this was frusemide, but a few patients were on bumetanide, usually 1–2 mg/day. Details are given in Table 3.


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  		Table 3 Diuretic usage

 
Captopril and lisinopril were the most commonly chosen ACE inhibitors. Enalapril and perindopril were used for fewer patients. A breakdown of the usage of ACE inhibitors is given in Table 4.


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  		Table 4 ACE inhibitor usage

 
3.6. Interviews with GPs
Sixteen GPs were involved in the interviews. They ranged in experience from GP registrars to principals of 25 years standing, with a mean of 10.6 years experience. Most doctors claimed to be conservative in their prescribing habits but were willing to use new treatments in specific cases. All three practices are above the district average for prescriptions of new drugs in general but only Practice A is above the average for cardiovascular drugs (Source: PACT report December 1997). No doctor claimed to be an enthusiast for new treatments and most generally preferred to await more evidence of effectiveness or use well established treatments. Selective Serotonin Re-uptake Inhibitors (SSRIs) were cited as an example of a new treatment that most doctors had used, but they were split between those encouraged by their effectiveness and those discouraged by side effects. Doctors’ views on the desirable characteristics of new drugs are given in Table 5.


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  		Table 5 Side effects

 
With respect to heart failure, all the doctors had used ACE inhibitors and considered them safe and effective. Six doctors stated no preference for the degree of heart failure in which they would use ACE inhibitors, with the remainder split between ‘moderate’ and ‘severe’ heart failure. Two doctors commented that objective investigations would add to their confidence in using ACE inhibitors in milder cases. All but two doctors had observed good results in heart failure patients treated with ACE inhibitors. Four had observed bad results, all patients who suffered adverse effects affecting renal function. Compliance with treatment was generally thought to be good. Doctors’ comments on side effects showed that cough was the only side effect seen more than occasionally. GPs indicated they would generally welcome a protocol for the administration of ACE inhibitors, and a few doctors noted the value of specific input from geriatricians. None of the doctors said they require an echocardiogram before using an ACE inhibitor, but most thought one was desirable. Several doctors commented that better access to echocardiograms would probably result in greater use of ACE inhibitors. Most doctors had experience of problems and delays in getting echocardiograms. The GPs favoured some form of open access echocardiography.

3.7. Interviews with hospital consultants
The consultants interviewed varied in experience from 1 month to 18 years as a consultant, with a mean of 10.2 years. All considered ACE inhibitors to be safe and effective. Five of the nine consultants stated no preference for the degree of heart failure in which they would use ACE inhibitors. Two consultants indicated they would probably use an ACE inhibitor if a patient required 40 mg or more of frusemide per day. All the consultants considered ACE inhibitors safe for commencement in general practice, although four considered the current usage in general practice to be variable and one considered usage to be poor. Just over half of the consultants thought that doses of ACE inhibitors should be increased toward target doses. Two consultants also pointed out a specific advantage that ACE inhibitors have over diuretics in not causing an untimely and potentially embarrassing diuresis in an elderly or incontinent patient. The consultants’ experience of side effects is given in Table 6. Again, cough was by far the most commonly observed side effect.


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  		Table 6 Side effects

 
Seven of the nine consultants had used angiotensin II blockers and although this experience was usually limited, most had formed the impression that side effects were less frequent on these drugs than on ACE inhibitors. None of the consultants thought an echocardiogram was necessary for every patient before an ACE inhibitor. Most thought one desirable, but with limited resources felt that echocardiograms should be reserved for patients with failed treatment or other complications. There was little enthusiasm for performing echocardiography on patients with long-standing hypertension or heart disease. Eight out of nine consultants felt that a direct access echocardiography service which operated under a clear policy was a satisfactory way of improving access for GPs.


   4. Discussion
Top
 Notes
 Abstract
 1. Introduction
 2. Method
 3. Results
 4. Discussion
References
 
A methodological weakness must be acknowledged in using case notes to perform an audit of this nature. Accuracy of this method relied on the completeness and accuracy of record keeping which will always vary within and between practices and areas. The case definition was also more likely to identify patients with severe disease, and would not identify asymptomatic patients at all. There was a further complication involved in the mixture of ascertainment methods for cases. Nevertheless, this method has been used in previous studies in general practice.

Interviews with practitioners are also subjective and reveal views and beliefs that may be anecdotal or based on variable degrees of evidence. Nevertheless, although practice aspires to greater degrees of evidence-based practice, much prescribing is still based on anecdote or experience rather than trial evidence. Hence, the study chose to address the views and beliefs of practitioners directly in order to try to understand better the areas that required to be addressed in a local policy.

The findings in this study, with an overall prevalence of heart failure of 1.1%, were close to the generally accepted estimate of 1% from the Framingham study. It is interesting that the Liverpool and London studies have such different prevalences from this study (Table 7). All were performed using the same basic method and in similar practice populations, yet the ‘true’ prevalence could not really differ by a factor of 4 unless there were remarkable differences between the populations studied. No satisfactory explanation was cited in the earlier papers to explain these differences, and it is difficult to be certain what the explanation is. It is likely that the true explanation relates to the difficulty of making a clinical diagnosis of heart failure and to the completeness of record keeping. Perhaps the increase in computer-based record systems may help reduce the variations in such records.


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  		Table 7 Comparative prevalences

 
In addition, all three studies looked at overall practice populations of between 17 000 and 30 000. The overall prevalence figures seen of approximately 1% in these studies are subject to the uncertainties of small numbers and the demographics of the populations. For example, in the younger age groups relatively few patients are identified and the overall prevalence was 0.2%. A substantially larger sample would be required to provide greater certainty about the estimate. However, standardised estimates can provide some reassurance, and using the European Standard Population (Table 8) reduced the overall prevalence in this study from 1.1 to 0.71% and in the Mair study from 1.5 to 1.15%.


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  		Table 8 Standardised populations

 
Another problem was the validity of clinical diagnosis of heart failure. Studies of the symptoms and signs of heart failure have shown a poor correlation with the presence of left ventricular dysfunction [19], although the discrepancy was less marked in those cases with more severe clinical disease. Yet heart failure is a condition that is diagnosed and monitored clinically and therefore, a clinical approach remained the pragmatic way to deal with it. Nevertheless, echocardiography is a key investigation for heart failure particularly where there is some diagnostic uncertainty. In this study, better treatment decisions were taken in the population that had been investigated with echocardiography. There was almost certainly a substantial number of patients who should have received ACE inhibitors and equally a population that received ACE inhibitors in whom they were not appropriate. Echocardiography would help sort these groups out, but consideration of how the service will be delivered is required.

The proportion of heart failure patients in receipt of ACE inhibitors was higher, at 50%, than some previously published studies. But this left another 50% with clinically defined heart failure who had not received an ACE inhibitor. In addition, typical doses used were disappointingly low, with mean and median doses less than half the target levels recommended in research trials. This could probably be partly explained by concern over side effects, which in turn could be better assured by a clear policy for blood monitoring of electrolytes and renal function.

The findings of this study have been presented to the Health Authority’s Cardiac Advisory Group, which brings together local GP representatives, hospital cardiologists and public health physicians. Heart failure has been adopted by the group as a priority area for action. With the advent of primary care groups, cash limited prescribing budgets will place further limitations on the extent to which all the competing strategies can be pursued. A pertinent recent example is that of statins, policies for which have been adopted in many districts. Criticism has been levelled at the cost effectiveness of statins [20]. The difficulty of balancing competing demands for investment is compounded by the difficulty of actually identifying and extracting savings later accrued in the secondary sector by earlier investments in primary care. These problems can only be overcome by effective joint working between general practitioners, PCGs, hospital consultants and the health authority to identify, research and develop solutions to address similar problems.


   Acknowledgements
 
We would like to thank the general practitioners and hospital consultants who participated in this study and willingly gave their time and their opinions. We would also like to thank their practice and office staff who were a great help in scheduling appointments.


   Notes
Top
 Notes
Abstract
 1. Introduction
 2. Method
 3. Results
 4. Discussion
 References
 
1 Then Senior Registrar in Public Health, North Cumbria HA, now Medical Manager, Biogen Ltd. Biogen is a biopharmaceutical company principally engaged in discovering and developing drugs for human healthcare through genetic engineering. No funding of any sort was used for this study. Back


   References
Top
 Notes
 Abstract
 1. Introduction
 2. Method
 3. Results
 4. Discussion
 References
 

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  3. McMurray J., Hart W., Rhodes G. An evaluation of the cost of heart failure to the National Health Service in the UK. Br J Med Econ (1993) 6:91–98.
  4. The SOLVD Investigators. Effects of enalapril on survival in patients with reduced left ventricular ejection fractions and congestive heart failure. N Engl J Med (1991) 325:293–302.[Abstract]
  5. Consensus Trial Study Group. Effects of enalapril on mortality in severe congestive heart failure. N Engl J Med (1987) 316:1429–1435.[Abstract]
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  7. Fourth International Study of Infarct Survival Collaborative Group ISIS-4. A randomised factorial trial assessing early oral captopril, oral mononitrate, and intravenous magnesium sulphate in 58 050 patients with suspected acute myocardial infarction. Lancet (1995) 345(8951):669–685.[CrossRef][Web of Science][Medline]
  8. Hall A.S. Murray G.D. Ball S.G. on behalf of the AIREX Study Investigators. Follow-up study of patients randomly allocated ramipril or placebo for heart failure acute heart failure after myocardial infarction: AIRE Extension (AIREX) Study. Lancet 1997; 349: 1493–1497.
  9. The SOLVD Investigators. Effects of enalapril on mortality and the development of heart failure in asymptomatic patients with reduced left ventricular ejection fractions. N Engl J Med (1992) 327:685–691.[Abstract]
  10. Hampton J.R. Results of clinical trials with diuretics in heart failure. Br Heart J (1994) 72:S68–S70.[Free Full Text]
  11. Cleland J., Poole-Wilson P.A. ACE inhibitors for heart failure: a question of dose. Br Heart J (1994) 72:106–110.[CrossRef]
  12. Houghton A.R., Cowley A.J. Why are angiotensin converting enzyme inhibitors underutilised in the treatment of heart failure by general practitioners? Int J Cardiol (1997) 59(1):7–10.[CrossRef][Web of Science][Medline]
  13. The ELITE Study Investigators. 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]
  14. Clarke K.W., Gray D., Hampton J.R. Evidence of inadequate investigation and treatment of patients with heart failure. Br Heart J (1994) 71:584–587.[Abstract/Free Full Text]
  15. Francis C.M., Caruana L., Kearney P. Open access echocardiography in management of heart failure in the community. Br Med J (1995) 310:634–636.[Abstract/Free Full Text]
  16. Murphy J.J., Frain J.P., Ramesh P., Siddiqui R., Bossingham C.M. Open access echocardiography to general practitioners for suspected heart failure. Br J Gen Pract (1996) 46:475–476.[Web of Science][Medline]
  17. Mair F.S., Crowley T.S., Bundred P.E. Prevalence aetiology and management of heart failure in general practice. Br J Gen Pract (1996) 46:77–79.[Web of Science][Medline]
  18. Parameshwar J., Shackell M.M., Richardson A. Prevalence of heart failure in three general practices in north west London. Br J Gen Pract (1992) 42:287–289.[Web of Science][Medline]
  19. Remes J., Miettinen H., Reunanen A., Pyorala K. Validity of clinical diagnosis of heart failure in primary health care. Eur Heart J (1991) 12:215–321.
  20. Freemantle N., Barbour R., Johnson R., Marchment M., Kennedy A. The use of statins a case of misleading priorities? Br Med J (1997) 315:826–827.[Free Full Text]

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