Low-density lipoprotein-cholesterol lowering for the primary prevention of cardiovascular disease among men with primary elevations of low-density lipoprotein-cholesterol levels of 190 mg/dL or above: analyses from the WOSCOPS (West of Scotland Coronary Prevention Study) 5-year randomized trial and 20-year observational follow-up

Background—Patients with primary elevations of LDL-C ≥190 mg/dL are at a higher risk of atherosclerotic cardiovascular disease as a result of long-term exposure to markedly elevated LDL-C levels. Therefore, initiation of statin therapy is recommended for these individuals. However, there is a lack of randomised trial evidence supporting these recommendations in primary prevention. In the present analysis we provide hitherto unpublished data on the cardiovascular effects of LDL-C lowering among a primary prevention population with LDL-C ≥190 mg/dL. Methods—We aimed to assess the benefits of LDL-C lowering on cardiovascular outcomes among individuals with primary elevations of LDL-C ≥190 mg/dL without pre-exiting vascular disease at baseline. We carried out post-hoc analyses from the West Of Scotland Coronary Prevention Study (WOSCOPS) randomised, placebo-controlled trial, and observational post-trial long-term follow-up, after excluding individuals with evidence of vascular disease at baseline. WOSCOPS enrolled 6595 men aged 45-64 years, who were randomised to pravastatin 40 mg/d or placebo. In the present analyses, 5529 participants without evidence of vascular disease were included, stratified by LDL-C levels into those with LDL-C <190 mg/dL (n=2969; mean LDL-C 178±6 mg/dL) and those with LDL-C ≥190 mg/dL (n=2560; mean LDL-C 206±12 mg/dL).The effect of pravastatin versus placebo on coronary heart disease (CHD) and major adverse cardiovascular events (MACE) were assessed over the 4.9-year randomised-controlled trial phase and on mortality outcomes over a total of 20-years of follow-up. Results—Among 5529 individuals without vascular disease, pravastatin reduced the risk of CHD by 27% (p=0.002) and MACE by 25% (p=0.004) consistently among those with and without LDL-C ≥190 mg/dL (p-interaction >0.9). Among individuals with LDL-C ≥190 mg/dL, pravastatin reduced the risk of CHD by 27% (p=0.033) and MACE by 25% (p=0.037) during the initial trial phase and the risk of CHD death, cardiovascular death and all-cause mortality by 28% (p=0.020), 25% (p=0.009) and 18% (p=0.004), respectively, over a total of 20-years of follow-up. Conclusions—The present analyses provide robust novel evidence for the short and long-term benefits of lowering LDL-C for the primary prevention of cardiovascular disease among individuals with primary elevations of LDL-C ≥190 mg/dL