Title

a. Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia.
b. Influence of pravastatin and plasma lipids on clinical events in the West of Scotland Coronary Prevention Study
(WOSCOPS).
c. Lipoprotein-associated phospholipase A2 as an independent predictor of coronary heart disease .

Purpose

a. To assess whether pravastatin therapy reduces the incidence of acute myocardial infarction and mortality from coronary heart disease in hypercholesterolemic men without a history of prior myocardial infarction.
b. To determine the extent to which reduction of LDL influenced coronary heart disease risk reduction in the WOSCOPS.
c. To evaluate whether inflammation is a predictor of risk in men with hypercholesterolemia

Design

a. Randomized, double blind, placebo controlled, multicenter.
b. Relationship between baseline lipid levels and rates of cardiovascular events; relationships between on-treatment lipid
concentrations and risk reduction in patients taking pravastatin were examined by Cox regression models and division of cohorts into quintiles.
c. 580 men who had had a coronary event were each matched for age and smoking status with 2 control subjects from the
same cohort who had not had a coronary event. Lipoprotein-associated phospholipase A2, C-reactive protein,
fibrinogen levels and the white cell count were measured at baseline, along with other traditional risk factors .

Patients

6595 men, 45-64 years of age, with fasting LDL cholesterol > 252 mg per deciliter before diet and > 155 mg per deciliter after 4 weeks of diet. None of the patients had a history of prior myocardial infarction. 78% of the patients were ex -or current smokers and 5% had angina pectoris.

Follow-up

5 years

Treatment regimen

Pravastatin (40 mg/d) or placebo

Results

• Compared to baseline values, pravastatin reduced plasma total cholesterol levels by 20% and LDL cholesterol by 26%,
whereas no such changes were observed in the placebo - treated group.
• Pravastatin reduced coronary events by 31% (p<0.001). There were 174 (5.5%) and 248 (7.9%) coronary events in
the pravastatin and control group, respectively.
• Pravastatin reduced the risk for nonfatal infarction by 31% (4.6% vs 6.5%; p<0.001), and the risk for death from all
cardiovascular causes by 32% (1.6 vs 2.3%; p=0.033).
• There was no increase in mortality from noncardiovascular causes.
• Baseline LDL cholesterol was only a weak predictor of cardiac risk in both treated and untreated groups. The reduction
in risk of a cardiac event by pravastatin was similar across all quintiles of baseline LDL levels.
• Baseline HDL showed a strong negative association with cardiovascular event rate, but reduction in risk with
pravastatin was similar for all quintiles of HDL elevation.
• The fall in LDL level in the pravastatin group did not correlate with the reduction in risk of a cardiac event on
multivariate regression.
• The maximum benefit of about a 45% risk reduction was observed in the middle quintile of LDL reduction,
representing a 24% fall in LDL.
• Further decreases in LDL, up to 39%, did not result in further reduction in coronary heart disease risk reduction. When
event rates between placebo and pravastatin - treated subjects with the same LDL cholesterol level were compared, there
was evidence for an LDL independent treatment benefit of pravastatin that remains to be determined.
• Levels of C-reactive protein, the white-cell count, and fibrinogen levels were strong predictors of the risk of coronary
events; the risk in the highest quintile of the study cohort for each variable was approximately twice that in the lowest
quintile. However the association of these variables with risk was markedly attenuated when age, systolic BP, and
lipoprotein levels were included in multivariate models.
• Levels of lipoprotein-associated phospholipase A2 had a strong positive association with risk that was not confounded
by other factors. It was associated with almost a doubling of the risk in the highest quintile as compared with the lowest
quintile.

Conclusion

• Primary prevention in moderately hypercholesterolemic men with 5 years pravastatin therapy reduced the incidence of myocardial infarction and death from cardiovascular causes. No excess of noncardiovascular death was observed.
• A fall in LDL cholesterol of 24% was sufficient to produce full benefit in patients taking pravastatin. Further reduction was not associated with further reduction in coronary heart disease risk.
• Elevated levels of lipoprotein-associated phospholipase A2 appear to be a strong risk factor for coronary heart disease.