WOSCOPS analysis supports LDL-C lowering for primary prevention at high LDL-c without risk assessment
LDL-Cholesterol Lowering for the Primary Prevention of Cardiovascular Disease Among Men with Primary Elevations of LDL-Cholesterol Levels of 190 mg/dL or Above: Analyses from the WOSCOPS 5-year Randomised Trial and 20-year Observational Follow-Up
Elevations of LDL-C ≥190 mg/dL are associated with a higher risk of atherosclerotic CVD in individuals without CVD [1,2]. Therefore, initiation of lipid-lowering therapy is recommended for individuals with primary elevations of LDL-C ≥190 mg/dL without the need for risk assessment, despite the lack of published randomized trial evidence supporting these recommendations in primary prevention. Furthermore, clinical guidelines have differed on whether to recommend percentage reductions in LDL-C or specific LDL-C levels among such patients [3,4].
In the present analysis of the WOSCOPS study, the CV effects of LDL-C lowering are reported in 5529 individuals with primary elevation of LDL-C ≥190 mg/dL without evidence of vascular disease at baseline [5,6]. Moreover, the relationship between reductions in LDL-C and on-treatment LDL-C levels with subsequent clinical events was evaluated.
In WOSCOPS, 6595 men with a mean age of 55 years were randomised to pravastatin 40 mg once daily or placebo, for a mean follow-up of 4.9 years. Patients were stratified by LDL-C levels at baseline.
Principle endpoints were as follows: CHD as the composite of definite or suspected non-fatal MI plus definite or suspected CHD death and MACE (CV death, non-fatal MI (definite or suspected) and non-fatal stroke).
- At 4.9 years, in individuals with LDL-C ≥190 mg/dL, pravastatin significantly reduced the risk of CHD by 27% (P=0.033) with a 25% lower risk of MACE (P=0.037) compared with placebo.
- Amongst all subjects initially allocated to pravastatin, CHD death, CV death and all-cause mortality were significantly reduced by 22%, 17% and 12% respectively during a total of 20-years of follow-up.
- The long-term risk of CHD death, CV death and all-cause mortality were significantly reduced by 28%, 25% and 18%, respectively, among those with LDL-C ≥190 mg/dL originally randomised to pravastatin.
- The ARR of death at 20 years from CHD, CV causes and from any-cause was at least two-fold greater among patients with LDL-C ≥190 mg/dL (ARR: 2.34%, 3.25% and 5.39%, respectively) compared with those with LDL-C <190 mg/dL.
- Among individuals with LDL-C ≥190 mg/dL, a reduction in LDL-C of greater than 30% or 39 mg/dL (1 mmol/L) on pravastatin was associated with a lower risk of CHD and MACE compared to placebo, whereas those individuals allocated to pravastatin whose LDL-C reduction was less than 30% or 39 mg/dL were not significantly different from placebo.
- For participants with a predicted 10-year atherosclerotic CVD risk below 7.5% and no DM, MACE was significantly reduced to 4.8% among those allocated to pravastatin in contrast to a rate of 7.5% among placebo, representing a 38% reduction in risk (HR: 0.62; 95% CI: 0.42 - 0.92; P = 0.018) during the 5-year trial period. During the 20-year extended follow up the corresponding rates were 18.76% vs 24.18%, representing a risk reduction of 27% (HR: 0.73; 95% CI: 0.60 - 0.90; P = 0.003).
Men with LDL-C levels ≥190 mg/dL without atherosclerotic CVD, have a 2-fold higher risk of major CV events than would be predicted with a risk calculator. These results provide evidence for the benefits of LDL-C lowering for the primary prevention of individuals with primary elevations of LDL-C ≥190 mg/dL, which may help reinforce current recommendations for this group of patients.