Cholesterol and coronary heart disease
An emphasis on reducing cholesterol levels in the treatment of coronary heart disease should not displace other cost-effective measures. Mary Turner-Boutle and colleagues on important findings
Coronary heart disease remains a major cause of premature death with high personal, social and economic costs. One of the risk factors for CHD is a raised cholesterol level although most people at high risk of CHD will have a combination of risk factors. Used alone, a measure of their cholesterol level will generally be a poor predictor of CHD.
The latest Effective Health Care bulletin considers the value of cholesterol screening and examines the clinical and cost-effectiveness of a range of interventions aimed at reducing CHD, with particular reference to 'statins', a relatively new class of cholesterol-lowering drugs.1
The bulletin concludes that population-wide cholesterol screening is unlikely to be cost-effective and cholesterol-lowering treatment using the statins is most cost-effective when targeted at those who are at high risk. Other methods of reducing CHD, such as reducing smoking, lowering high blood pressure, and using aspirin and beta blockers after myocardial infarction are more cost-effective and should be used before cholesterol- lowering drugs (see box below).
Although blood cholesterol is an important risk factor for CHD, other major independent risk factors (such as smoking, obesity, physical inactivity, high blood pressure and diabetes) also need to be considered in attempts to define population-based or individual risk of the disease. Smokers with high blood pressure, for example, have three times the risk of dying from CHD compared with non-smokers who have normal blood pressure but identical levels of blood cholesterol.
A blood cholesterol measure used alone is a poor predictor of an individual's risk of CHD; the majority of CHD events occur in people who do not have a raised cholesterol level. Attempts at defining 'high-risk' individuals using blood cholesterol alone will misclassify many people into either high or low-risk categories, which may lead to inappropriate treatment.
In addition, there can be considerable error in the measurement of individual blood cholesterol through the use of poorly calibrated laboratory equipment or with the increasing use of the less accurate compact measuring devices in GP surgeries.
Cholesterol levels can be lowered by several types of intervention, diet and drugs being the most important.
Diet The effectiveness of low-fat diets depends critically on how restrictive they are and the degree of adherence to them. Dietary changes have produced substantial reductions in blood cholesterol in settings where patients' diets are controlled by others, but studies within the general population have shown only small effects.
Drugs Statins, a new class of powerful cholesterol-lowering drugs are able to reduce blood cholesterol levels by more than 20 per cent. They have also been shown to reduce morbidity. Their older counterparts (eg fibrates) are less effective and may even be harmful in lower-risk patients.
Cholesterol lowering is not necessarily the most important among the range of effective interventions to reduce CHD risk. Risk can be reduced significantly by lifestyle changes such as giving up smoking. Drug treatments which lower blood pressure, beta blockers following myocardial infarction, and aspirin can significantly reduce CHD events in high-risk patients.
Smoking Smoking cessation advice given in a primary care setting has a small but important effect on long-term behaviour.
Oily fish and Mediterranean diet An increased intake of oily fish has been shown to reduce cardiovascular mortality after heart attack, and significant reductions in CHD were found in a trial of a 'Mediterranean' diet, even though neither approach reduced cholesterol levels. These findings appear potentially to be very important and these trials need replicating.
Exercise It is estimated that a sedentary lifestyle doubles an individual's risk of death from CHD. A computer simulation based on epidemiological evidence has estimated that a 25 per cent increase in the proportion of the population undertaking moderate activity would produce the equivalent of life years gained by a 2 per cent reduction in the proportion of smokers within the population.
Drugs Aspirin appears to reduce mortality among people at high risk of myocardial infarction who have not previously experienced an event. Anti- hypertensive medication reduces the risk of CHD mortality among people with high blood pressure.
There are significant potential savings from preventing CHD events and their associated treatment and hospitalisation costs. The role of cholesterol- lowering drugs must, however, be considered alongside other appropriate options. Several interventions have been found to be more cost-effective than the use of statins. An economic evaluation illustrates the range of costs per life-year gained for a range of interventions, taking into account the projected savings from reduced admissions and treatment for clinical events avoided (see box top right).
Evidence suggests that if treated with aspirin and anti-hypertensive drugs, and helped to stop smoking and change diet, over half of those at increased risk of CHD might have their risk reduced sufficiently to make statin treatment unnecessary or relatively cost-ineffective. If a patient remains at significantly high risk of CHD after employing more cost-effective options, the use of a statin may be appropriate and consideration will need to be given to which statin to use. Expenditure on statins in 1997 was over pounds113m, having risen significantly from pounds20m in 1993. If the different statins available were equally efficacious and safe, it would appear preferable to use those with the lowest cost per percentage reduction in cholesterol. However, only two of the statins available in the UK have been the subject of trials evaluating their effect on clinical outcomes rather than just cholesterol levels. Since the clinical effects of the cheaper statins have not been evaluated, the extent to which they will reduce mortality and morbidity is uncertain.
Cholesterol-lowering interventions confer significant benefits for those at high risk of CHD, many of whom, by British standards, have average levels of cholesterol. Over-emphasis on cholesterol levels is likely to result in a failure to identify and treat those at high risk of CHD and a focus on treating those without significant risk purely on the basis of their moderately elevated cholesterol levels. It is probably worth measuring cholesterol only in patients who have either a strong family history of CHD or other easily identifiable risk factors, and in order to monitor patients on cholesterol-lowering drugs or diets.
The evidence for the effectiveness of statins is strong in people with cardiovascular disease or diabetes who are at high risk of CHD events. However, the cost per life-year gained from the use of statins is high when compared with some other drug treatments and lifestyle changes which can produce net savings in healthcare resources.
It is of concern that many people who might benefit from treatment for hypertension or the use of anti-platelet agents and beta blockers following myocardial infarction are not receiving these treatments. There is evidence of considerable unmet potential for the cost-effective reduction of risk in patients with established coronary disease. Priority should be given to ensuring that appropriately targeted interventions which are clearly more cost-effective are actually being used in practice.
A recent statement by the Standing Medical Advisory Committee to health authorities and GPs on the use of statins recommended prioritising treatment for people with established CHD, and suggested that treating people with an annual risk of a CHD event of under 3 per cent is unlikely to represent value for money. Using a threshold rate of 3 per cent, around 700,000 people in England would be eligible for statins, in addition to those who have already had a CHD event. Pressure to treat more people with statins is high and increasing. If the threshold for treatment dropped to 1.5 per cent, almost 5 million people would become eligible. Widespread prescribing would be extremely costly and represent poor value for money.
Scoring systems are available to help estimate an individual's overall risk of CHD and enable clinicians to make treatment decisions. Research is required into patient preferences for different treatment options. Consideration should be given to means of assisting discussion of the relative risks due to modifiable risk factors and the effects of various interventions.
The major public health approaches to lowering population levels of risk factors for CHD remain the control of smoking, the reduction of hidden fats and calories in the diet, and the encouragement and extending of facilities for physical activity throughout life. Clinically, the most important issues are to concentrate on patients with established CHD; use anti-hypertensive drugs, beta blockers and aspirin before using statins; and reserve the use of statins for patients who remain at high risk of CHD after using the more cost-effective drug treatments, and following the management of other risk factors.
1 Effective Health Care February 1998; 4 (1). Cholesterol and Coronary Heart Disease: screening and treatment.
Effective Health Care bulletins provide NHS decision makers with information on the effectiveness and cost-effectiveness of interventions and the delivery and organisation of healthcare. The Department of Health funds a limited number of bulletins for distribution within the NHS. Inquiries should be addressed to: NHS centre for reviews and dissemination, York University, York YO1 5DD. Tel: 01904- 433634; fax: 01904 433661; e-mail: firstname.lastname@example.org
This work was funded by the NHS Health Technology Assessment Programme.
Mary Turner-Boutle is a research fellow and Trevor Sheldon director at the NHS centre for reviews and dissemination, York University. George Davey Smith is professor at the department of social medicine, Bristol University, and Shah Ebrahim is professor at the Royal Free Hospital school of medicine. Modelling of cost-effectiveness estimates was undertaken by the school for health and related research, Sheffield University.