A recent study published in Circulation has analysed data from the WOSCOPS (West of Scotland Coronary Prevention Study) 5-year randomized trial and 20-year observational follow-up, and the results have provided much-needed data for improving outcomes in patients with LDL-C ≥190 mg/dL who are over 21 years of age. [1]

This group is defined as one of the key statin benefit groups in the 2013 American College of Cardiology/ American Heart Association cholesterol guidelines. However, prior to this study there was no randomized clinical trial evidence for statin therapy in this patient population.

Researchers performed a post hoc analysis from the WOSCOPS randomized, placebo-controlled trial, along with observational post-trial 20-year follow up. Here, 5529 men aged 45 to 64 years who were randomly assigned to pravastatin 40 mg/d or placebo were included. The participants did not have evidence of vascular disease at baseline. The effect of pravastatin and placebo was analysed with respect to the impact on coronary heart disease and major adverse cardiovascular events.

Pravastatin was shown to reduce the risk of coronary heart disease by 27% (P=0.002) and major adverse CVD events by 25% (P=0.004). This was consistent in patients with and without LDL-C ≥190 mg/dL, all of whom had no prior evidence of vascular disease. Overall, in the patients initially randomised to pravastatin, CHD death, CVD death and all-cause mortality were reduced by 22%, 17% and 12%, respectively.

This study addressed the lack of evidence for primary prevention in patients with LDL-C ≥190 mg/dL, which is to be welcomed. However, the study did have some limitations. The study lacked genetic criteria for patients with familial hypercholesterolaemia (FH), although the results are applicable to the FH patient population. Furthermore, the study was conducted in a male-only population, the population in terms of ethnicity was not diverse, and there were relatively high levels of smoking in these patients. [2]

An editorial that accompanied these study results discussed the implications of this research, with the authors stating that: “We can now say definitively that statin treatments of primary prevention patients with LDL-C ≥190 mg/dL lead to significant reductions in cardiovascular events and total mortality.” [2]

Current guidelines recommend reducing LDL-C levels in these patients to ≥50% using high intensity statin therapy. However, the emergence of PCSK9 inhibitors and ezetimibe means that these can be used in addition to maximal statin therapy to reduce adverse events in these patients. [2]

However, even though the evidence gap has now been closed, the bridge between research and clinical practice must still be crossed. The authors argue that perhaps the biggest challenge is to encourage clinicians to adopt these recommendations into their clinical practice.

References

1. Vallejo-Vaz A, Robertson M, Catapano A.L, et al. Low-Density Lipoprotein Cholesterol for the Primary Prevention of Cardiovascular Disease Among Men with Primary Elevations of Low-Density Liporpotein Cholesterol Levels of 190 mg/dL or Above: Analysis from the WOSCOPS (West of Scotland Coronary Prevention Study) 5-year Randomized Trial and 20-Year Observational Follow-Up. Circulation 2017; 136: 1878-1891.
2. Watson K.E, Fonarow G. Closing the Remaining Evidence Gap: Randomized Controlled Trial Data to Support Statin Therapy for Low-Density Lipoprotein LDL-C ≥190 mg/dL. Circulation 2017; 136: 1892-94.