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ACE Inhibitors in the treatment of chronic heart failure: Effective and cost-effective

Chronic heart failure (CHF) is the syndrome of breathlessness, fatigue and fluid retention resulting in an impaired ability of the heart to pump properly. The commonest causes are coronary heart disease (CHD) and primary heart muscle diseases (cardiomyopathies), with heart valve disease less common. Heart failure is over-diagnosed (especially in the elderly) and is best confirmed using cardiac ultrasound [1]. Only a minority of people in the community with suspected CHF receive this investigation [2].

The size of the problem

The size of the CHF problem in a health authority with a population of 250,000 and based on a prevalence of 1% [3,4] is shown below:-

CHF is a serious condition with mortality ranging from 50% over 5 years in mild heart failure [3] to 60% per year in severe cases [5]; these figures are higher than breast and prostate cancer death rates.

About 1% of the NHS budget is devoted to CHF, with 60% spent on hospital admissions [6]. Between 25% and 30% of heart failure patients are admitted every year and CHF accounts for 5% of all medical admissions to hospital [7]. Quality of life for heart failure sufferers is poor and worse than some other chronic diseases such as diabetes and chronic lung disease [8]. The CHF problem will increase (the so-called heart failure epidemic [9]) because of the impact of treatment on other forms of CHD (for example thrombolysis) and the ageing population.

Using ACE inhibitors in CHF

Treatment of CHF aims to improve:-
  • Symptoms
  • Functional capacity
  • Quality of life
  • Prognosis (survival)


If the cause of heart failure is atrial fibrillation, irregular beating of the heart, the first choice medicine remains digoxin, as it has been for hundreds of years. Diuretics are the most effective treatment for heart failure symptoms [8], but do not improve prognosis. A number of randomised trials have convincingly demonstrated that angiotensin converting enzyme inhibitors (ACEIs) improve symptoms and survival in all grades of heart failure when given with diuretics [8]. A number of ACEIs have been used in trials and the results suggest that the effect is class rather than drug specific. However, enalapril is the best studied drug at present but there are cheaper alternatives (such as ramipril).

The results of two major RCTs involving enalapril demonstrate the beneficial effects. One RCT involved 253 patients with severe congestive heart failure; half were treated with enalapril 2.5 to 40 mg per day. There was a 40% reduction in mortality rate at 6 months and a 31% reduction at 12 months - with all the benefit in patients with progressive heart failure, where the reduction in mortality was 50%.

The second RCT involved 2569 patients with chronic heart failure and reduced left ventricular ejection fractions treated with 2.5 to 20 mg enalapril per day with a follow up averaging 41 months. Enalapril use resulted in a 16% reduction in mortality risk (95% confidence intervals 5-26%); the largest reduction in mortality was seen in patients with progressive heart failure (22% risk reduction, 95% CI 6-35%). There was a significant reduction in the number of hospital admissions with enalapril by about 30%.

A comparison of the effectiveness of some of the commonly used cardiovascular drugs demonstrates the beneficial effects of enalapril, as shown in the Table.



Everyone with CHF who has been stabilised with diuretics should be considered for having an ACEI added to their therapy, unless there are specific contraindications (such as aortic stenosis [10]). Currently, only about 10% of CHF patients are on ACEI.

In a health authority of 250,000 people, around 40 deaths and 300 hospital admissions could be prevented each year using ACEIs.

Most people (around 98%) could have treatment started in general practice [11], especially as three ACEIs are licensed for this purpose. Fears about hypotension and renal failure (which meant more people starting treatment in hospital) have been overstated, especially when first doses are low and sensible guidelines followed to detect patients at risk [8].

Problems with ACEIs

These medicines are generally well tolerated and some of the early problems were because of the high doses used. Cough is a well known problem, but is also common with people with CHF who aren't treated (31% of controls and 37% of enalapril treated patients in trials) and is less of a problem than in patients given ACEIs for hypertension. However, only 1% of people stopped treatment because of their cough. Other adverse effects include rash, taste disturbance and impaired renal function.

Current areas of uncertainty for ACEIs

There are two areas of uncertainty, firstly whether asymptomatic people with left ventricular dysfunction should be treated, and secondly, what is the optimal therapeutic dose.

Studies are in progress to answer these questions.

Direct costs of introducing ACEIs

The impact of introducing ACEIs to patients with CHF in a health authority of 250,000 people over 1 year have been calculated based on published economic analyses [6,12]. The analysis suggests that a net saving could be made by introducing an ACEI to patients if the 98% in whom it was appropriate had treatment started in general practice. The balance between overall savings and costs depends on the proportion of patients whose treatment is initiated by the GP:



Note: SOLVD results [11] for reduced admission rates, improved survival and usual enalapril dose (20 mg od). Includes capital and revenue costs of an extra echocardiogram machine plus costs of echoes for every patient with CHF. These will be less in subsequent years. Two extra visits to GP per patient per year for monitoring therapy (Fourth National GP Morbidity Survey), extra biochemical tests (to exclude renal impairment) are included. Costs are direct NHS costs for 1990/1 [6,12].

Conclusion

Large improvements in the quality and quantity of life for people with CHF could be achieved by using ACEIs appropriately. Treatment could be introduced at minimal cost to the NHS and might achieve savings. However, costs and savings would be unevenly distributed: primary care would pick up most of the prescribing costs and no apparent savings; the acute sector would pick up capital and revenue costs of echocardiography and any potential savings from reduced hospital admissions. If we are to encourage evidence-based prescribing in this area, these issues need addressing soon.
Dr Simon Sanderson
Senior Registrar in Public Health Medicine
Cambridge and Huntingdon Health Commission

References:

  1. NM Wheeldon, TM MacDonald, CJ Flucker et al. Echocardiography in chronic heart failure in the community. Quarterly Journal of Medicine 1993 86: 287-9.
  2. J Parameshawar, PA Poole-Wilson, GC Sutton. Heart failure in a district general hospital. Journal of the Royal College of Physicians of London 1992 26: 139-42.
  3. PA McKee, WP Castelli, PA McNamara, WB Kannel. The natural history of congestive heart failure: the Framingham study. New England Journal of Medicine 1971 285: 1441-6.
  4. WB Kannel, AJ Belanger. Epidemiology of heart failure. American Heart Journal 1991 121: 951-7.
  5. CONCENSUS Trial Study Group. Effects of enalapril on mortality in severe congestive heart failure. New England Journal of Medicine 1987 316: 1429-35.
  6. J McMurray, W Hart, G Rhodes. An evaluation of the cost of heart failure to the National Health Service in the UK. British Journal of Medical Economics 1993 6: 99-110.
  7. GC Sutton. Epidemiological aspects of heart failure. American Heart Journal 1990 120: 1538-40.
  8. J McMurray, HJ Dargie. Diagnosis and management of heart failure. British Medical Journal 1994 308: 321-8.
  9. JGF Cleland. Heart failure: the epidemic of the millennium. Hospital Update 1994 January; 9-10.
  10. Editorial. Failure to treat heart failure. Lancet 1992 339: 278-9.
  11. The SOLVD Investigators. Effect of enalapril on survival in patients with reduced left ventricular ejection fractions and congestive heart failure. New England Journal of Medicine 1991 325: 1468-75.
  12. W Hart, G Rhodes, J McMurray. The cost effectiveness of enalapril in the treatment of chronic heart failure. British Journal of Medical Economics 1993 6: 91-8.

Questions to be answered

Q: What need is met by this treatment?
A: Improved quality and length of life for CHF patients, coupled with likely savings for the NHS.
Q: What happens at present?
A: Only about 10% of CHF patients receive ACEIs. Most could have the medicine safely prescribed for them.
Q: How does this improve effectiveness or quality?
A: Each health district of 250,000 could reduce deaths by 40 a year and hospital admissions by 300 per year.
Q: What is the capital cost?
A: Small - probably one echocardiogram per district.
Q: What is the revenue cost per case?
A: The revenue cost per case of CHF treated with ACEIs is £300 per year.
Q: What is the likely total cost per million population? (capital or depreciation plus cost/case times number of cases)
A: About £3.6 million.
Q: Will this increase or decrease total cost of secondary care?
A: Secondary care costs could be reduced by around £800,000 in an authority of 250,000 if the expected reduction in hospital admissions occurs.
Q: What is the effect on total cost?
A: Could be as high as an increase in £900,000 (revenue plus capital/depreciation) in an authority of 250,000 if 40% of patients were admitted to hospital for initiation of treatment. The lower the proportion of patients admitted to hospital for initiation of treatment, the lower would be the effect on total cost.
Q: What cost savings are likely?
A: Cost savings as high as £60,000 could be achieved in an authority of 250,000 if only 2% of patients have treatment initiated in hospital as inpatients and if the expected reduction in hospital admissions occurs.

Advice to health authorities and GP fundholders

  • Will increase quality and effectiveness.
  • Will increase/decrease total cost of care.
  • Include in specification.



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