In men with a low-density lipoprotein (LDL) cholesterol level of 190 mg per dL (4.92 mmol per L) or higher, are statins effective as primary prevention?
These results confirm that the use of statins for men with an LDL cholesterol level of at least 190 mg per dL, regardless of calculated risk, is associated with a clinically and statistically significant reduction in cardiovascular events and probably cardiovascular and all-cause mortality. (Level of Evidence = 1b–)
The most recent American College of Cardiology/American Heart Association lipid guidelines recommend a statin for any patient with an LDL cholesterol level of 190 mg per dL or higher. However, the evidence supporting this recommendation is limited. The West of Scotland Coronary Prevention Study (WOSCOPS), originally published in 1995, was one of the first studies of statins for primary prevention. It enrolled men 45 to 64 years of age with an LDL level of at least 155 mg per dL (4.01 mmol per L) and randomized them to receive pravastatin (Pravachol), 40 mg, or placebo. The mean age of the study population was 55 years, the mean body mass index was 26 kg per m2, and the mean LDL cholesterol level was 192 mg per dL (4.97 mmol per L).
These authors reanalyzed the data, limiting their analysis only to primary prevention by excluding anyone with any possible evidence of vascular disease, and adding a 20-year observational follow-up. They stratified the results by LDL cholesterol level of 190 mg per dL or higher (n = 2,560) vs. LDL level of less than 190 mg per dL (n = 2,969). The researchers found a fairly consistent relative reduction in cardiac events with the use of statins, regardless of the initial LDL level. For the combined outcome of cardiovascular death, myocardial infarction, and stroke, the relative risk reduction was 25% for those with an initial LDL level of at least 190 mg per dL. There were favorable trends (not statistically significant) regarding all-cause mortality and cardiovascular death with the use of statins. For the combined outcome of nonfatal myocardial infarction and coronary heart disease death, there was a significant benefit for those with an initial LDL level of less than 190 mg per dL (hazard ratio = 0.58; 95% confidence interval, 0.41 to 0.81), but not for those with an initial LDL level of 190 mg per dL or higher.
Results were generally consistent during the 20-year follow-up period, although this time the reductions in all-cause mortality and cardiovascular death were statistically significant for the group with an initial LDL of 190 mg per dL or higher. The results from a subgroup analysis of patients without diabetes mellitus and a less than 7.5% 10-year event risk were similar. A limitation of this study is generalizability to a contemporary U.S. population: The WOSCOPS participants were all men, 44% smoked, and less than 2% had type 2 diabetes.
Study design: Randomized controlled trial (double-blinded)
Funding source: Government
Setting: Outpatient (any)
Reference: Vallejo-VazAJRobertsonMCatapanoALet alLow-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. Circulation2017;136(20):1878–1891.