Abstract
Background Genetic studies suggest that the relative risk reduction (RRR) of statins may increase over time, potentially resulting in much greater long-term benefit if statins are started before cardiovascular (CV) risk is high.
Methods We used a nationally representative sample of American adults to estimate effects of initiating a statin when 10-year CV risk reaches 5%, 10% or 15%. We examined scenarios in which a statin’s initial RRR (30%) gradually doubles over 10 to 30 years of treatment.
Results Initiating a statin when 10-year CV risk is 5% resulted in a mean of 20.1 years on a statin before age 75 (8 years more than starting when CV risk reaches 10%). If a statin’s RRR doubles over 20 years, starting when CV risk is 5% would save about 5.1 to 6.1 additional QALYs per 1000 additional treatment years than starting when CV risk is 10%. Most of this additional benefit was accrued by those who reach a 5% risk at a younger age. Due to the prolonged treatment period, however, early treatment could also result in net harm if the treatment slowly increased a major complication of aging, such as muscular or neurological aging.
Conclusions In a thought experiment exploring the impact of delayed effects, we found that if the relative effectiveness of statin therapy gradually doubles over a 10 to 30 year period, starting a statin when 10-year CV risk is 5% could have much more long-term benefit than starting a statin when CV risk is 10%. Most of the additional benefit occurred in those at elevated age-adjusted CV risk. Unfortunately, given the long duration of treatment, substantial delayed statin harms, if present, could outweigh these potential benefits and result in substantial net harm.
Footnotes
↵* RAH and GJS are co-first authors. RAH conceived of the study, set analysis goals and parameters, and drafted the Introduction, Results and Discussion sections; GJS independently developed and refined the statistical model needed to answer the study questions, conducted all analyses, and drafted the Methods section and Technical Appendices. They are listed in alphabetical order.
Financial support for this study was provided in part (for JBS and RAH) by grants from the Department of Veterans Affairs HSR&D (IIR 06-253), and the Michigan Center for Diabetes Translational Research (NIDDK of The National Institutes of Health [P60 DK-20572]). The funding agreement ensured the authors’ independence in designing the study, interpreting the data, writing, and publishing the report.