Letter by Löwe et al Regarding Article, “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”

Vallejo-Vaz et al¹ sought to determine the potential long-term benefits of lipid-lowering therapy in the primary prevention of atherosclerotic cardiovascular diseases over 20 years. Their post hoc analysis of 15-year observational follow-up data in WOSCOPS (West of Scotland Coronary Prevention Study), a large randomized controlled trial in Scotland, showed that pravastatin reduced major adverse cardiovascular events in the long term among 2560 apparently healthy men with high low-density lipoprotein cholesterol ≥190 mg/dL at baseline. However, their study did not answer the core question: Will providing statins to people at low risk of atherosclerotic cardiovascular diseases lower their risk even more?

We disagree with the authors’ recommendation to initiate lipid-lowering therapy for every patient with low-density lipoprotein cholesterol ≥190 mg/dL without estimating each patient’s cardiovascular risk, and believe clinicians should not follow this blanket recommendation for prescription. The largest problem with the study is that it does not represent the general population. The authors excluded men with prior atherosclerotic cardiovascular diseases from their analyses, but the WOSCOPS population had a median predicted 5-year cardiovascular risk of 9.2%, according to the Cholesterol Treatment Trialists’ Collaboration meta-analysis,² which corresponds to a 10-year cardiovascular risk of ≈18%. This indicates that the population Vallejo-Vaz et al studied probably had an intermediate- to high-risk profile. Extrapolating these results to the general population, most of whom are at low risk of coronary heart disease, is unwarranted. In the United States, for example, only ≈5.5 million people aged ≥21 years have low-density lipoprotein cholesterol levels ≥190 mg/dL, so this group makes up ≈2% of the population.³

There are other reasons not to generalize. Over 40% of study participants were active smokers, a major cardiovascular risk factor, but smoking is now much less prevalent in Scotland (the World Health Organization estimated it at ≈18%) and many other countries. Women were also excluded from the study, although they make up a large part of the low-risk population. Applying the findings of Vallejo-Vaz et al too broadly could lead to overprescribing statins⁴ and very expensive PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitors.

We also question the equations Vallejo-Vaz et al used to stratify risk for a European population in their secondary analyses, which included two-thirds of the primary prevention cohort, for those with no diabetes mellitus and a predicted 10-year atherosclerotic cardiovascular diseases risk <7.5%. The results of this secondary analysis were similar to the overall study results. The Pooled Cohort Risk Equations are not well validated across ethnic groups and for women, whereas other equations may be better calibrated and more discriminating.⁵

For careful interpretation, it should also be highlighted that the present analyses have been funded in part by a grant from Sanofi to Imperial College London.

The study by Vallejo-Vaz et al does not address the question of whether hypercholesteremic patients with a low-risk profile should be blindly prescribed statins. Others have also disputed this recommendation because it may lead to widespread overprescription of medication that has potential adverse effects.⁴ Estimating each patient’s individual risk is crucial to determining the correct course of treatment.