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Updated: Feb 1, 2026

In Silico Clinical Trials for Cardiovascular Disease
Published on: May 27, 2022
Finding the Balance Between Benefits and Harms When Using Statins for Primary Prevention of Cardiovascular Disease: A
Henock G Yebyo1, Hélène E Aschmann1, Milo A Puhan1
1University of Zurich, Zurich, Switzerland (H.G.Y., H.E.A., M.A.P.).
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 risk above which statins provide net benefit.
Design:
Quantitative benefit-harm balance modeling study.
Data Sources:
Network meta-analysis of primary prevention trials, a preference survey, and selected observational studies.
Target Population:
Persons aged 40 to 75 years with no history of CVD.
Time Horizon:
10 years.
Perspective:
Clinicians and guideline developers.
Intervention:
Low- or moderate-dose statin versus no statin.
Outcome Measures:
The 10-year risk for CVD at which statins provide at least a 60% probability of net benefit, with baseline risk, frequencies of and preferences for statin benefits and harms, and competing risk for non-CVD death taken into account.
Results Of Base-Case Analysis:
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.
Results Of Sensitivity Analysis:
Most alternative assumptions led to similar findings.
Limitation:
Age-specific data for some harms were not available.
Conclusion:
Statins provide net benefits at higher 10-year risks for CVD than are reflected in most current guidelines. In addition, the level of risk at which net benefit occurs varies considerably by age, sex, and statin type.
Primary Funding Source:
Swiss Government Excellence Scholarship Office, Béatrice Ederer-Weber Foundation, and North-South Cooperation at the University of Zurich.
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