Elsevier

The Lancet

Volume 348, Issue 9038, 16 November 1996, Pages 1339-1342
The Lancet

Articles
West of Scotland Coronary Prevention Study: identification of high-risk groups and comparison with other cardiovascular intervention trials

https://doi.org/10.1016/S0140-6736(96)04292-4Get rights and content

Summary

Background

We assessed the potential benefit of treatment for low-risk and high-risk groups in the West of Scotland Coronary Prevention Study (WOSCOPS) population, and compared the benefits of primary and secondary prevention of coronary heart disease (CHD) by lipid lowering with the benefits of blood pressure reduction in the primary prevention of stroke.

Methods

We did a subgroup analysis of placebo-treated men in the WOSCOPS population by age, vascular disease at trial entry, and other established risk factors. We also compared WOSCOPS findings with those of the Scandinavian Simvastatin Survival Study (4S) and the Medical Research Council (MRC) trial of treatment for mild to moderate hypertension in middle-aged men. The WOSCOPS population comprised 6595 men aged 45–64 years with no history of myocardial infarction (MI) and plasma total cholesterol concentrations of 65–80 mmol/L at initial screening. Participants were randomly allocated pravastatin (40 mg daily) or placebo, and followed up for an average of 49 years.

Findings

Coronary event rates at 5 years in the WOSCOPS placebo group were higher than 10% (the recommended treatment threshold) in men with pre-existing vascular disease and in those 55 years or older without symptoms or signs of CHD but with at least one other risk factor. Event rates were low in men with hypercholesterolaemia but no other risk factor: 35% (95% CI 13–57) for men aged 45–54 years and 5 3% (27–80) for men aged 55–64 years. Three times more men had to be treated for 5 years to prevent one endpoint in WOSCOPS than in 4S. By contrast, two to four times fewer men with hyperlipidaemia were treated to save one coronary event in WOSCOPS than hypertensives to save one stroke in the MRC trial. These differences persisted after adjustment for the low-risk status of many of the patients with hypertension who took part in the MRC trial.

Interpretation

There were a substantial number of men whose risk of a coronary event was more than 10% at 5 years in the WOSCOPS cohort. The absolute benefit of pravastatin treatment of hyperlipidaemia is less in the primary prevention of CHD than in secondary prevention, but is similar to that for primary prevention of stroke by treatment of mild to moderate hypertension in middle-aged men.

Introduction

After publication of the West of Scotland Coronary Prevention Study (WOSCOPS)1 of pravastatin in men with hypercholesterolaemia we decided to re-examine the role of lipid-lowering drugs in the prevention of coronary heart disease (CHD). WOSCOPS showed that in men aged 45–64 years who had raised serum cholesterol (6-5-8-0 mmol/L), but no previous myocardial infarction (MI), pravastatin treatment reduced the relative risk of non-fatal MI or death definitely attributable to CHD by 31%, that of death definitely or probably related to CHD by 33%, that of death from all cardiovascular causes by 32%, and that of death from any cause by 22%. The absolute risks of these endpoints at 5 years were reduced by 2–4%, 0–6%, 0–7%, and 0–9%, respectively. The proportionate benefit from pravastatin was similar in all subgroups of patients.1

The findings of WOSCOPS could, in theory, be applied to a substantial proportion of many populations2 and would lead to widespread drug treatment. However, this approach may not be desirable or economically feasible because of the constraints on modern health-care systems. Our examination of the issue of the benefit of treatment starts from the position that there is a wide range of absolute risk for CHD morbidity and mortality in our cohort; with a uniform proportionate risk reduction, there should be a corresponding variation in the absolute benefit of treatment.

As a precursor to a detailed examination of cost benefit, we did a subgroup analysis of the WOSCOPS population to identify the characteristics of the men at the highest absolute risk of CHD. We also compared the effect of cholesterol lowering on primary prevention of CHD (as shown in WOSCOPS) with that of secondary prevention by lipid lowering (Scandinavian Simvastatin Survival Study, 4S)3 and treatment of high blood pressure on the risk of stroke in middle-aged men (MRC trial of mild to moderate hypertension).4

All analyses in this paper were based on the premise that the threshold for drug treatment should be determined by CHD (or stroke) event risk, and not simply by serum cholesterol (or diastolic blood pressure). We believe that absolute, rather than relative, risk reduction provides a better estimate of the benefits of treatment, and that the best way to present results is to calculate the number of patients who need to be treated to prevent (or delay) one event. This statistic can be derived easily because it is the reciprocal of the absolute risk reduction.5 Our identification of high-risk subgroups within the WOSCOPS population was based on the assumption that most clinicians would treat an individual with a one in ten chance (10% risk) of a major cardiovascular event within 5 years. If we assume the distribution of coronary events over time is uniform, this risk would equate to a risk of 20% in 10 years, which is the accepted threshold for vigorous risk-factor management by the task force of the European Societies of Cardiology, Atherosclerosis, and Hypertension.6

Section snippets

Methods

The study design of WOSCOPS has been described previously.7 At randomisation, the WOSCOPS population consisted of 6595 men aged 45–64 years with no previous history of MI and two fasting values of low-density lipoprotein (LDL) cholesterol of more than 40 mmol/L (one >4–5 mmol/L and at least one <60 mmol/L), after dietary advice. Patients were randomly allocated pravastatin (40 mg daily) or placebo, and were followed up for an average of 4–9 years. The primary endpoint was non-fatal MI or death

Results

The 5-year risk of non-fatal MI or death definitely or probably attributable to CHD in WOSCOPS placebo-treated participants is shown in table 1. Men aged 45–54 years who had minor ECG abnormalities, preexisting vascular disease, or who were current smokers had event rates of more than 10% at 5 years. We excluded patients with pathological Q waves, horizontal or downward sloping ST depression with STj of 1 mm or more, or T wave inversion of 5 mm or more. Smaller ST-T changes were defined as

Discussion

WOSCOPS was the first primary prevention trial of lipid-lowering drug therapy to show a reduction in all-cause mortality. Treatment with pravastatin significantly reduced the risk of MI and death from cardiovascular causes in middle-aged men with moderate hypercholesterolaemia and no history of MI. The risk of death from any cause was reduced by 22% in the pravastatin group (p=0–051 by log rank test, p=0–036 after adjustment for baseline risk factors). There was no increase in

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