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

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Abstract

Background:

Patients with primary elevations of low-density lipoprotein cholesterol (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 randomized 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 In the present analysis, we provide hitherto unpublished data on the cardiovascular effects of LDL-C lowering among a primary prevention population with LDL-C ≥190 mg/dL.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 preexisting vascular disease at baseline. We performed post hoc analyses from the WOSCOPS (West of Scotland Coronary Prevention Study) randomized, placebo-controlled trial, and observational posttrial long-term follow-up, after excluding individuals with evidence of vascular disease at baseline. WOSCOPS enrolled 6595 men aged 45 to 64 years, who were randomly assigned 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 and major adverse cardiovascular events were assessed over the 4.9-year randomized 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 coronary heart disease by 27% (P=0.002) and major adverse cardiovascular events 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 coronary heart disease by 27% (P=0.033) and major adverse cardiovascular events by 25% (P=0.037) during the initial trial phase and the risk of coronary heart disease 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.

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