Background: Many guidelines use expected risk for cardiovascular disease (CVD) during the next 10 years as a basis for recommendations on use of statins for primary prevention of CVD. However, how harms were considered and weighed against benefits is often unclear.

Objective: To identify the expected CVD risk above which low- or moderate- dose statins provide net benefit for a primary prevention population and additionally to assess their variation across different age groups, sex, and by statin type.

Methods: We performed a quantitative benefit–harm balance modeling study to determine 10-year risk for CVD at which statins provide at least a 60% probability of net benefit, with baseline risks, frequencies of and patient preferences for statin-related benefits and harms, and competing risk for non-CVD death taken into account. We took data from network meta-analysis of primary prevention trials, and a preference elicitation survey, which were conducted to inform this study as well as selected observational data.

Results: Younger men had net benefit at a lower 10-year risk for CVD than older men (14% for ages 40 to 44 years vs. 21% for ages 70 to 75 years). In women, the risk required for net benefit was higher (17% for ages 40 to 44 years vs. 22% for ages 70 to 75 years). Atorvastatin and rosuvastatin provided net benefit at lower 10-year risks than simvastatin and pravastatin.

Conclusions: Statins provide net benefits at higher 10-year risks for CVD than are reflected in most current guidelines. In addition, the level of risks where net benefit occurs varies considerably according to age, sex, statin type and populations. These results imply that the current guidelines might be over prescribing statins for a large proportion of primary prevention populations, especially for older people who likely have higher risk of harms, such as diabetes, myopathy etc., which would offset the benefit of statins.