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Statins: whom should we treat?

 

Clinical bottom line

Different guidelines apply to variable proportions of patients, and produce different numbers of patients who should be treated with lipid lowering drugs.


National guidelines for the prevention of coronary heart disease identify modification of lipid profiles, and particularly reduction of low density lipoprotein cholesterol (LDL-C), as a major target. These guidelines should help doctors to decide in which patients to start treatment. In the UK doctors probably turn first to the Joint British Societies recommendations [1], but in Europe the Joint European Societies recommendations [2] and in the USA the National Cholesterol Education Program (NCEP) [3] are used. There are others.

The guidelines all agree that attempts to reduce the incidence of CHD should start with education and therapeutic lifestyle changes, including stopping smoking, stress reduction, increased physical activity, weight reduction and dietary modification. Comorbid conditions, such as hypertension and diabetes, should be controlled appropriately.

Nearly all patients with established CHD will be eligible for lipid-lowering drug therapy. For primary prevention things are more complicated. First we need a form of risk assessment, and then we need recommendations on the level of risk at which drug treatment should be started.

A recent study has compared the current guidelines for primary prevention of CHD to determine whether they agree or differ in their assessments of CHD risk and their recommendations for lipid-lowering therapy [4]. The guidelines compared were:

Participants were 100 consecutive patients without clinical evidence of cardiovascular disease who attended a University outpatient lipid and diabetes clinic. Data was collected for age, sex, blood pressure, smoking, diabetes, family history of premature CHD, LVH on ECG, total, HDL and LDL cholesterol (T-C, HDL-C, LDL-C), and trigyceride levels.

Risk Assessment

PROCAM guidelines are based on data from the Munster Heart Study, while the others are based on data from the Framingham Heart Study. For this reason, the authors chose to use the risk calculated using the Framingham equation as a gold standard to which risks calculated using the other guidelines were compared.

Table 1. Level of agreement between guidelines on CHD risk.

  Framingham NCEP ATP III Joint European Joint British Revised Sheffield PROCAM
Total patients
100
100
100
100
100
100
Patients included in guidelines
87
93
81
72
95
22
 
All guidelines applicable to a total of 62 patients
CHD risk 20% or more over next 10 years
21
33*
16**
20**
CHD risk 15% or more over next 5 years
8
3
CHD risk 20% or more over next 10 years
10 (of 22)
3
Agreement (kappa)   Fair (0.22) Good (0.64) Very good (0.81) Poor (less than 0.2) not calculated
* only 19 of 21 patients identified by Framingham were identified by NCEP ATP III
** all included in 21 patients identified by Framingham

 


Recommendations

Four of the available guidelines make recommendations concerning lipid-lowering therapy.

Table 2. Comparison of guidelines for recommendation of lipid-lowering therapy

NCEP ATP III
Joint European
Joint British
Revised Sheffield
Criteria for recommending lipid-lowering therapy dependent on LDL-C, CHD risk and number of risk factors CHD risk over 20% over 10 years,T-C over 190 mg/dL and/or LDL-C over 115 mg/dL CHD risk over 15% over 10 years and T-C over 5 mmol/L CHD risk over 3% per year
Number (of 100) recommended for treatment 32 16* 22** 3
* only 11 included in NCEP ATP III recommendations
** only 14 included in NCEP ATP III recommendations

 


Comment

This analysis was carried out on data from a relatively small number of patients from a specialised segment of the population, but is in agreement with two previous studies [8, 9].

The algorithms for risk assessment were not applicable to all patients. In this study Framingham, NCEP, Joint European and Revised Sheffield could be applied to at least four out of every five patients, and Joint British to seven out of every ten, while PROCAM was inappropriate for any population other than middle-aged men (less than one in five of this population). To be useful, algorithms need to be widely applicable.

The algorithms also provided different estimates of risk; a patient at significant risk according to one guideline could be low-risk according to another; Joint British was in best agreement with the Framingham equation in this study.

Finally, those guidelines that make recommendations for initiation of lipid-lowering therapy use differing criteria, which result in different, but overlapping, sets of patients who are considered eligible. This reflects different priorities and constraints rather than disagreement, but may contribute to confusion about who to treat. The greater number of patients identified for treatment by the NCEP ATP III guidelines probably reflects the fact that these guidelines have been most recently updated, incorporating the growing evidence of benefit in a wider range of patients.

Bandolier thinks this is all rather confusing, but we must remember that guidelines, estimates and recommendations are not intended to give a definitive answer to treat or otherwise, but to help in the process of making a decision about an individual patient within the limits of available resources.

Reference

  1. D Wood et al. Joint British recommendations on prevention of coronary heart disease in clinical practice. Heart 1998 80(suppl 2): 1-29.
  2. K Pyorala, D Wood D. Prevention of coronary heart disease in clinical practice. European recommendations revised and reinforced. European Heart Journal 1998 19: 1413-5.
  3. Executive summary of the third report of the National Cholesterol Education Program (NCEP) expert panel on detection, evaluation, and treatment of high cholesterol in adults (Adult Treatment Panel III). JAMA 2001 285: 2486-97.
  4. UC Broedl et al. Comparison of current guidelines for primary prevention of coronary heart disease. J Gen Intern Med 2003 18: 190-5.
  5. KM Anderson et al. Cardiovascular disease profiles. Am Heart J 1990 121: 293-8.
  6. LE Ramsay et al. Targeting lipid-lowering drug therapy for primary prevention of coronary disease: an updated Sheffield table. Lancet 1996 348:387-8.
  7. G Assmann et al. Simple scoring scheme for calculating the risk of acute coronary events based on the 10-year follow-up of the Prospective Cardiovascular Munster (PROCAM) Study. Circulation 2002 105: 310-5.
  8. PN Durrington et al. Indications for cholesterol-lowering medication: comparison of risk-assessment methods. Lancet 1999 353: 278-81.
  9. AS Wierzbicki et al. A comparison of algorithms for initiation of lipid-lowering therapy in primary prevention of coronary heart disease. J Cardiovasc Risk 2000 7:63-71.