Cholesterol-lowering therapy

Advisory report | 19-07-2000

In this advisory report, the Cholesterol Committee of the Health Council of the Netherlands presents a brief summary of what is known about the relationship between a high cholesterol level in the blood and the development of coronary heart disease and about the effects of statins. The Committee uses this as the basis for substantiating the indications it believes ought to apply for starting a cholesterol-lowering therapy. In closing, the Committee briefly discusses some scientific developments that may have consequences for the prevention of coronary heart disease.

The Committee concludes:

• Treatment with statins leads to a reduction in the risk of fatal and nonfatal manifestations of coronary heart disease (CHD) and, in people with manifest cardiovascular disease (CVD), to a reduction in the risk of ischaemic vascular disease.
• general, be it coronary, cerebrovascular or peripheral, by approximately 30%.
• This relative reduction of the CHD (and CVD) risk is clearly substantiated by the results of randomized clinical trials for men and women aged up to 70. It is not yet possible to make any definite statement about the effect of statins in people aged over 70.
• It appears from current data that the degree to which statins reduce the CHD risk is more or less independent of whether clinical manifestations of CVD have previously occurred, whether other cardiovascular risk factors are involved and, insofar as a particular threshold has been exceeded, of the cholesterol concentration level.
• The precise cholesterol concentration above which statins are effective is not yet clear. The Committee assumes that cholesterol-lowering therapy is not worthwhile if the total cholesterol (TC) level is 5 mmol/l or lower.
• Statins are generally well tolerated. No serious side-effects are expected over a period of five to ten years. Health risks over a period of ten years or longer are improbable.

The Committee makes the following recommendations:

• Patients with familial hyperlipidaemia should be treated with cholesterol-lowering drugs that suit their specific lipid profile.
• Cholesterol-lowering therapy is highly recommended for patients with manifest cardiovascular disease and a TC level that exceeds the target value of 5 mmol/l.
• Cholesterol-lowering therapy should be considered for patients with diabetes mellitus if the TC level exceeds 5 mmol/l and if one of the following is present: a CHD risk score of at least 8, microalbuminuria or left ventricular hypertrophy. The CHD risk score is defined as: n + the ratio TC/HDL (the ratio of total and high density lipoprotein cholesterol concentrations), where n equals the number of risk factors at issue in the person concerned. The following are considered to be risk factors: diabetes mellitus, hypertension, smoking and the occurrence of CHD before the age of sixty in first-degree relatives.
• The TC/HDL ratio should be determined in all persons with diabetes mellitus, manifest CVD or signs or a family history indicative of familial hyperlipidaemia.
• Cholesterol-lowering treatment should be started only after determination of an average TC/HDL ratio, on the basis of at least two independent measurements. This restriction does not apply after an acute cardiovascular event: in that case, treatment with a statin may be started on the basis of a single cholesterol measurement in a blood sample taken upon admission.
• With regard to starting cholesterol-lowering therapy in persons over 70 years of age, restraint should be exercised.
• Smokers should be encouraged to stop smoking, if necessary with help of a specific intervention. Nicotine-replacement therapy is an essential part of an effective smoking cessation policy and should be generally available.
• Lifestyle advice aimed at promoting a healthy diet and sufficient physical exercise should form an important part of any cholesterol-lowering therapy.
• Statins are the first choice medication for treating people with hypercholesterolaemia.
• A TC concentration of 5 mmol/l or lower should be the goal of cholesterol-lowering therapy.
• Standardization of HDL cholesterol measurements should be promoted in the Netherlands to enable the correct prescription of cholesterol-lowering therapy.

The Committee could not reach agreement about the indications for cholesterol-lowering therapy in people without familial hyperlipidaemia, manifest cardiovascular disease or diabetes mellitus.

The majority of the Committee sees as its task to make a statement about the indications for which cholesterol-lowering therapy is medically worthwhile, without considering the cost of statins. These Committee members do not address the question when statin treatment should qualify for reimbursement from the collective health care budget. They recommend that:

• cholesterol-lowering treatment should be considered if the TC concentration exceeds 5 mmol/l and there is either a CHD risk score of at least 8, or left ventricular hypertrophy
• cholesterol-lowering therapy should not be considered for people aged under 40, leaving aside exceptional cases where a high TC/HDL ratio and multiple risk factors are at issue
• cholesterol-lowering therapy should initially focus on reducing the CHD risk through lifestyle advice, in which to stop smoking would be the most important recommendation; if the results of lifestyle advice were insufficient, treatment with a statin would be the next step
• the TC/HDL ratio should be determined for all persons aged 40 or over, who have hypertension or first-degree relatives with CHD before the age of sixty.

Three members of the Committee believe that the costs of statins form an essential part of the problem of determining the indications for cholesterol-lowering therapy. They concur with the existing consensus ’Cholesterol’ of the CBO, the Dutch National Organization for Quality Assurance in Hospitals. They believe that people who do not suffer from cardiovascular disease, diabetes or severe lipid disorders should not be considered to be candidates for cholesterol-lowering therapy, with the exception of a small group of middle-aged male smokers with multiple risk factors. According to this minority of the Committee, a democratic decision should be taken as to whether the cost of statins ought to be reimbursed for this last group.

In closing, the Committee examines some current and forthcoming scientific developments. Numerous randomized trials are currently underway that will provide new information about the effect of statins, especially in women and elderly people. Recent research has provided new insights into the development of CHD. The Committee discusses the role of hyperhomocysteinaemia, coagulation-promoting factors, infections and genetic factors. None of these new developments is sufficiently advanced to enable the Committee to indicate the consequences for the practice of CHD prevention.