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Primary Prevention for LDL-C ≥190 mg/dl
Study Questions:
Do statins reduce cardiovascular risk among a primary prevention population with low-density lipoprotein cholesterol (LDL-C) levels ≥190 mg/dl?
Methods:
This was a post-hoc analysis using data from the WOSCOPS (West Of Scotland Coronary Prevention Study) trial to examine cardiovascular outcomes among participants with primary elevations of LDL-C ≥190 mg/dl who did not have pre-existing vascular disease at baseline. WOSCOPS enrolled 6,595 men (aged 45-64 years) who were randomized to pravastatin 40 mg/d or placebo. Participants in the present analysis were stratified by LDL-C levels into those with LDL-C <190 mg/dl (n = 2,969; mean LDL-C 178 ± 6 mg/dl) and those with LDL-C ≥190 mg/dl (n = 2,560; mean LDL-C 206 ± 12 mg/dl). The primary outcomes of interest were occurrence of coronary heart disease (CHD) and occurrence of major adverse cardiovascular events (MACE). Outcomes were assessed over the 4.9-year randomized controlled trial phase, and mortality outcomes were assessed over 20 years of follow-up.
Results:
A total of 5,529 participants were included in the present analysis. Mean (± standard deviation) LDL-C at baseline was 206 ±12 mg/dl among patients with LDL-C ≥190 mg/dl, and 178 ± 6 mg/dl among those with LDL-C <190 mg/dl. Percentage reduction in LDL-C from baseline with pravastatin among those with and without LDL-C ≥190 mg/dl was of a similar magnitude (approximately 23% at year 1 and 19.5-20% at the end of the trial). Pravastatin reduced the risk of CHD by 27% (p = 0.002) and MACE by 25% (p = 0.004) in both participants with an LDL-C ≥190 mg/dl and in those with an LDL-C <190 mg/dl. Long-term risks of CHD death, cardiovascular death, and all-cause mortality were significantly reduced by 28%, 25%, and 18%, respectively, among participants with LDL-C ≥190 mg/dl originally randomized to pravastatin. The absolute reduction in the risk (ARR) of death at 20 years from CHD, cardiovascular causes, and 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, reduction in LDL-C of >30% or 39 mg/dl (1 mmol/L) was associated with a lower risk of CHD and MACE compared with placebo.
Conclusions:
The authors concluded that the present analysis provides 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.
Perspective:
These data support the recommendations for statin therapy among adults with LDL-C levels of ≥190 mg/dl who are at increased risk for CVD.
Keywords: Cardiovascular Diseases, Cholesterol, LDL, Coronary Artery Disease, Dyslipidemias, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Lipids, Pravastatin, Primary Prevention, Risk Factors, Vascular Diseases
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